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Patent
Eye Technology Care, French Institute of Health and Medical Research | Date: 2016-10-14

A device for treatment of an ocular pathology characterized in that it comprisesat least one eye ring (1) wherein the proximal end of said eye ring (1) is suitable to be applied onto the globe and means (2,17) to generate ultrasound beam fixed on the distal end of the eye ring (1), said means to generate ultrasound beam presenting a concave segment shape conformed along a single curvature corresponding to a single direction wherein the concavity is designed to be tuned towards the eyeglobe.


Patent
Institute Curie, French National Center for Scientific Research, French Institute of Health, Medical Research, Assistance Publique Hopitaux De Paris and University of Paris Descartes | Date: 2016-07-29

A composition that can be used as a vaccine containing means for targeting at least one antigen to dendritic cells and as adjuvants a granulocyte macrophage colony stimulating factor and a CpG oligodeoxynucleotide and/or a CpG-like oligodeoxynucleotide. This composition can used to treat cancers, infectious diseases caused by bacterial, viral, fungal, parasitic or protozoan infections, allergies and/or autoimmune diseases.


Patent
French Institute of Health, Medical Research and University Paris Diderot | Date: 2015-04-09

The present invention relates to a method for preventing Gram-negative bacterial colonization of an oropharyngeal material, the said method comprising bringing into contact a composition comprising a cranberry-derived proanthocyanidin extract on at least a part of the surface area of the said material.


Patent
French Institute of Health and Medical Research | Date: 2016-11-08

The invention relates to Histamine H4 receptor antagonists or inhibitors of Histamine H4 receptor gene expression for the treatment and/or the prevention of vestibular disorders.


The invention relates generally to neuroprotection and repair in neurological disorders involving Tan dysfunction (including Alzheimers disease). The invention describes AND INCLUDES a direct interaction between proteins FKBP52 mid Tau. More particularly, the invention relates to a method for screening a drug for the prevention and treatment of neurological disorders involving Tau dysfunction comprising the following steps: a) determining the ability of a candidate compound, to modulate the interaction between a Tan polypeptide and a FKBP52 polypeptide and b) selecting positively the candidate compound that modulates said interaction. The present invention finally relates to diagnostic, prognostic, and monitoring assays of neurological disorders involving Tau dysfunction.


Patent
French Institute of Health and Medical Research | Date: 2015-04-16

The present invention relates to polypeptides and uses thereof for reducing CD95-meditated cell motility. In particular, the present invention relates to a polypeptide having an amino acid sequence having at least 70% of identity with the amino acid sequence ranging from the amino-acid residue at position 175 to the amino-acid residue at position 191 in SEQ ID NO:1.


Patent
French Institute of Health, Medical Research, Assistance Publique Hopitaux De Paris and Indiana University | Date: 2016-11-17

The present invention relates to methods for preventing and treating chronic kidney disease (CKD).


Patent
French Institute of Health, Medical Research, French National Center for Scientific Research, Genethon, University of Paris Descartes, École Nationale Supérieure de Chimie de Paris, University of Évry Val d'Essonne and Assistance Publique Hopitaux De Paris | Date: 2016-09-16

The present invention relates to a method for treating a Leber congenital amaurosis in a patient harbouring the mutation c.2991+1655 A>G in the CEP290 gene, comprising the step of administering to said patient at least one antisense oligonucleotide complementary to nucleic acid sequence that is necessary for preventing splicing of the cryptic exon inserted into the mutant c.2291+1655 A>G CEP290 mRNA


Patent
French Institute of Health, Medical Research and Montpellier University | Date: 2016-11-21

The present invention relates to a method for selecting a competent oocyte or a competent embryo by determining the expression level of specific microRNA species in a body fluid or in cumulus cells.


The invention relates to the field of cell therapy, particularly NK cell mediated therapy. The present invention relates to a method of producing an ex vivo population of cells, preferably NK cells, from at least two umbilical cord blood units (UCB units), or fraction thereof containing said cells, by pooling said at least two UCB units to produce said population of cells. The present invention relates to the use of said cells, preferably NK cells, obtainable or obtained by the process according to the invention, as a composition for therapeutic use, preferably for the treatment of cancer and chronic infectious disease.


Patent
Institute Pasteur Paris, French Institute of Health and Medical Research | Date: 2015-03-09

A method for keeping leukocytes alive ex vivo or in vitro, comprising maintaining the leukocytes in a medium comprising from 3 to 10 mM of glucose, in hypoxic conditions with P(02)10 mM Hg.


Patent
French Institute of Health, Medical Research, Montpellier University and University Dauvergne | Date: 2015-04-24

The present invention relates to a compound of formula (I) wherein: i is 0 or 1; j is 0 or 1; k is 0 or 1; R_(1 )and R_(2 )are in particular H, (C_(1)-C_(12))alkyl, or a group of formula C(O)R; R is a, linear or branched, alkyl radical, comprising at least 19 carbon atoms; R_(3 )is H and k=0 when j=1; or, when j=0, R_(3 )is C(O)R or -L-C(O)R; L, U and L are linkers; wherein, when j=0, at least one of the groups R_(1); R_(2 )and R_(3 )comprises a radical R.


Patent
French Institute of Health, Medical Research, University of Paris Descartes, Fondation Imagine, Assistance Publique Hopitaux De Paris Aphp, French National Center for Scientific Research, University Grenoble Alpes, French Atomic Energy Commission and University of Burgundy | Date: 2015-02-18

The present invention relates to methods and pharmaceutical compositions for the treatment of diseases mediated by the NRP-1/OBR complex signaling pathway. In particular, the present invention relates to a method for treating a disease selected from the group consisting of cancers, obesity and obesity related diseases, anorexia, autoimmune diseases and infectious diseases in a subject in need thereof comprising administering the subject with a therapeutically effective amount of an antagonist of the NRP-1/OBR signaling pathway.


Patent
French Institute of Health, Medical Research, Montpellier University, Assistance Publique Hopitaux De Paris, University Paris Est Creteil and University of Angers | Date: 2016-10-17

The present invention relates to methods and pharmaceutical compositions for cardioprotection of subjects who experienced a myocardial infarction. In particular, the present invention relates to a ligand of the sonic hedgehog signaling pathway for use in the cardioprotection of a subject who experienced a myocardial infarction.


Patent
French Institute of Health, Medical Research, University of Paris Descartes and Assistance Publique Hopitaux De Paris Aphp | Date: 2015-04-29

The present invention relates to methods and pharmaceutical compositions for treating vaso-occlusive crises. In particular, the present invention relates to a method of treating a vaso-occlusive crisis in a subject in need thereof comprising administering to the subject a therapeutically effective amount of agent capable of degrading, destabilizing or depleting the blood-borne extracellular DNA from the blood of the subject.


Patent
Association Institute Of Myologie, French National Center for Scientific Research, French Institute of Health, Medical Research, University Pierre and Marie Curie | Date: 2015-04-14

The present invention relates to compositions and methods for treating myotonic dystrophy.


Patent
French Institute of Health and Medical Research | Date: 2016-11-04

The present invention relates to methods for diagnosing and treating iron overload and iron deficiency.


Patent
French Institute of Health, Medical Research, Aix - Marseille University and Gfrs Groupe Francophone Of Recherche Sur La Sclerodermie Systemique | Date: 2015-03-12

The present invention relates to an in vitro method for diagnosing lupus in a subject, said method comprising the step of detecting in a biological sample obtained from the subject the autoantibody recognizing the protein biomarker THEX1. More, the invention relates to kits and array useful for carrying out diagnosis methods according to the present invention.


The present invention stems from the finding that the extracellular domain of CD31 proteins present on blood leukocytes is shed and released in the circulation as a soluble form of CD31. A method for detecting shed CD31 is further disclosed. The invention therefore relates to a method for detecting a shed ectodomain of a transmembrane protein such as CD31 and to the use of such a method as a diagnostic tool. The invention further provides methods for determining whether a candidate protein is part of a molecular complex.


Patent
French Institute of Health, Medical Research, University Paris Diderot, University of Paris 13 and Assistance Publique Hopitaux De Paris | Date: 2016-11-22

The present invention relates to various soluble forms of CD31, including a novel form which is shed by activated platelets and released into the circulation. Methods for detecting said soluble forms of CD31 are disclosed, as are methods of specifically 1 detecting said platelet-derived shed CD31 and the use of such methods as a diagnostic tool.


Patent
Institute Pasteur Paris, French Institute of Health, Medical Research and Assistance Publique Hopitaux De Paris | Date: 2017-04-19

A massive clonal expansion of activated CD8^(+) T-cells with increased frequency of HPV 16-specific CD8^(+) T-cells was discovered to be a characteristic of oral lichen planus (OLP), indicating a causal link between HPV infection and the dysimmune process. The invention relates to compositions and methods for the diagnosis and treatment of OLP patients.


Belzung C.,French Institute of Health and Medical Research | Willner P.,University of Swansea | Philippot P.,Catholic University of Louvain
Current Opinion in Neurobiology | Year: 2015

Major depression is a psychiatric disorder with high prevalence. Both specialists in cognitive psychopathology and neurobiologists have proposed explanations of the process/systems that exhibit altered functioning during this disorder. Psychological processes that are dysfunctional in depressed patients include alterations in self-referential schemas, cognitive biases, ruminations and processing mode (over-general versus concrete). These cognitive processes are associated with altered function of specific brain systems, including prefrontal areas and cingulate cortex (both involved in self-referential processes and rumination), amygdala (cognitive bias), lateral habenula (cognitive bias) and hippocampus (cognitive bias and overgeneral processing). This review aims to present a coherent view integrating these two approaches in a unique model. © 2014 Elsevier Ltd.


Patent
National University of Singapore, French Institute of Health and Medical Research | Date: 2016-04-13

Modifications of the biomaterial poly(vinyl alcohol) with surface topographical cues, attachment factors for its improved performance, and/or sustained release of vascular endothelial biochemical cue for application as a vascular graft scaffold is described. Furthermore, novel fabrication methods to pattern the poly(vinyl alcohol) hydrogel in planar film or tubular form with the topographies in the lumen are disclosed.


Patent
French Institute of Health, Medical Research and University Rene Descartes | Date: 2014-10-07

The present invention concerns a method for the screening of antibacterial substances comprising a step of determining the ability of a candidate substance to inhibit the activity of a purified enzyme selected from the group consisting of: (i) a D-aspartate ligase comprising a polypeptide having an amino acid sequence possessing at least 50% amino acid identity with an amino acid sequence selected from the group consisting of SEQ ID No 1 to SEQ ID No 10, or a biologically active fragment thereof; and (ii) a L,D-transpeptidase comprising a polypeptide having an amino acid sequence possessing at least 50% amino acid identity with the amino acid sequence of SEQ ID No 11, or a biologically active fragment thereof.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2011.2.3.3-1 | Award Amount: 15.69M | Year: 2011

In recent years, an increased number of zoonotic viruses and bacteria have crossed the species barrier to humans and caused or threatened to cause human pandemics with high morbidity and mortality. Because of our inability to predict the emergence of these pathogens, it is difficult to take preventive measures. It is known that zoonotic pathogens need to cross barriers at the animal-human interface, at the pathogen-host interface within humans, and at the human-human interface before they can cause a human pandemic. However, it is poorly understood which pathogen, host, arthropod vector, and environmental factors allow zoonotic pathogens to successfully cross these barriers. Therefore, our overall objective is to identify the key factors that render zoonotic pathogens prone to cross the species barrier and gain efficient transmissibility among humans. ANTIGONE has a two-pronged approach to reach this objective. First, we will perform primary research studies to fill important gaps in our understanding of how zoonotic pathogens can gain pandemic potential. These studies will focus on selected viruses and bacteria, including SARS coronavirus, , Crimean-Congo haemorrhagic fever virus, Nipah virus, Ebola virus, E. coli, M. bovis, B. burgdorferi, C. burnetii and S. suis. Integral to these activities will be a cross-disciplinary training programme for young scientists (Young ANTIGONE) and a web-based pathogen information sharing platform. Second, we will organize Dahlem studies where experts from the human and veterinary fields, from within and outside ANTIGONE, will discuss key issues in infectivity, pathogenicity, and transmissibility of zoonotic pathogens and determine general criteria to assess the risk of these pathogens to gain human pandemic potential. Together, the results of these activities will improve our ability to model and predict potential human pandemics of zoonotic origin and to develop effective and timely preventive measures.


ERANID, the European Area Network on Illicit Drugs, aims to improve cooperation in drug research in order to allow well-founded policy decisions. ERANID works both in the demand field and in the supply field. ERANID will promote multidisciplinary research activities in the field of socio-economic sciences and humanities. This may cover e.g. emerging drugs, vulnerable groups, changing demographics of drug using populations, and the impact of drugs on health inequalities and social deprivation. It may also cover patterns in drug markets and the drug-crime nexus. Closer cooperation between researchers in different countries will also lead to a further development of research methodologies, which can be of special importance for the evaluation of policies and programmes. Overcoming fragmentation in drug research and developing a common Strategic Research Agenda (SRA) are key objectives of ERANID. To do this, ERANID will first take stock of research programmes and research projects. By making the results of this exercise easily accessible, ERANID will help researchers and policy makers to find information and avoid unnecessary duplication of research. ERANID will consult stakeholders (e.g. scientific community, treatment centre organisations, patient organisations, police and justice). Analysis of the results will help to find gaps and to set priorities for research that will profit most from an international and interdisciplinary approach. Bringing together funding bodies in EU Member States and other countries, involving policy makers and other stakeholders will help to create consensus about the research priorities. These issues will all inform the SRA, from which the priorities for two joint research calls will be selected. ERANID starts as a consortium of eleven partners from six EU Member States. Other organisations from a number of European and other countries will be kept closely informed and associated to this initiative. ERANID is meant as first step towards a longer term cooperation in the field of drugs research.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2010.4.2-1 | Award Amount: 7.36M | Year: 2010

Assuming an annual birth rate of 10.25 births/1,000 population approximately 25,000 Extremely Low Gestational Age Newborns are born every year in the EU. Conservative figures estimate that approximately half of all these babies will develop low blood pressure and require treatment. However, no uniform criteria exist to define hypotension and the evidence to support our current management strategies is limited. Many of these interventions have been derived from adult literature and have not been validated in the newborn. Dopamine remains the most common inotrope used despite little evidence that it improves outcome. Hypotension is not only associated with mortality of preterm infants but is also associated with brain injury and impaired neurosensory development in ELGAN survivors. Preterm brain injury has far reaching implications for the child, parents, family, health service and society at large. It is therefore essential that we now design and perform the appropriate trials to determine whether the infusion of inotropic agents is associated with improved outcome. We have assembled a consortium with expertise in key areas of neonatal cardiology, neonatology, neurophysiology, basic science and pharmacology with the intention of answering these questions. The objectives of the group are as follows: 1. To perform a multinational, randomized controlled trial to evaluate whether a more restricted approach to the diagnosis and management of hypotension compared to a standard approach, with dopamine as a first line inotrope, affects survival without significant brain injury at 36 weeks gestational age in infants born less than 28 weeks gestation and affects survival without neurodevelopmental disability at 2 years corrected age 2. To perform pharmacokinetic and pharmcodynamic studies of dopamine 3. To develop and adapt a formulation of dopamine suitable for newborns in order to apply for a Paediatric Use Marketing Authorization


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2011.2.3.1-4 | Award Amount: 4.02M | Year: 2012

Respiratory tract infections (RTIs) are a huge burden in terms of mortality and morbidity worldwide. To improve the management of the bacterial infections of the respiratory tract, the institution of an appropriate antimicrobial therapy as soon as possible has also been shown to be a key element for reducing morbidity and mortality. The aim of our project is to develop a panel of dedicated rapid diagnostic tests to allow the medical staff to link antibiotic prescription on evidence-based diagnosis. In our 3 year project, combining the Multiplex Ligation-dependent Probe Amplification (MLPA) and microfluidic technologies will allow to address the question of viral or bacterial origin. In the case of a bacteria, a second step will allow to identify which bacteria is of interest with its virulence factors and resistance mechanisms. This new tool will be developed for efficient use in clinical settings in order to allow for a better antibiotic resistance management. Several direct impacts will be observed either on public health (decrease of antibiotic pressure), efficiency of treatment for patients (decrease of infectivity and speed in accurate treatments), for diagnostic laboratories (improve in turn around time), for SMEs (better competitiveness) and more generaly on technological innovations.


Grant
Agency: Cordis | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2015-ETN | Award Amount: 3.90M | Year: 2015

The Phosphoinositide 3-kinase (PI3K) pathway is at the core of multiple fundamental biological processes controlling metabolism, protein synthesis, cell growth, survival, and migration. This inevitably leads to the involvement of the PI3K signalling pathway in a number of different diseases, ranging from inflammation and diabetes to cancer, with PI3K pathway alterations present in almost 80% of human cancers. Therefore, PI3Ks have emerged as important targets for drug discovery and, during 2014, the first PI3K inhibitor was approved by FDA in the US for the treatment of a lymphocytic leukaemia. Nonetheless, our understanding of PI3K-mediated signalling is still poor and only a fraction of the potential therapeutic applications have been addressed so far, leaving a large amount of translational work unexplored. Europe features a set of top quality research institutions and pharmaceutical companies focused on PI3K studies but their activities have been so far scattered. This proposal fills this gap by providing a multidisciplinary network (biochemistry, mouse studies, disease models, drug development, software development) and an unprecedented training opportunity from the bench to the bedside (from pre-clinical discoveries to clinical trials), through cutting edge molecular biology, drug discovery and clinical trial organization. The proposal is aimed at training young investigators in deep understanding of the different PI3K isoforms in distinct tissues and to translate this knowledge into a new generation of PI3K inhibitors, treatment modalities and into identify new uses for existing PI3K inhibitors.


Grant
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: PHC-25-2015 | Award Amount: 5.00M | Year: 2016

C3-Cloud will establish an ICT infrastructure enabling a collaborative care and cure cloud to enable continuous coordination of patient-centred care activities by a multidisciplinary care team and patients/informal care givers. A Personalised Care Plan Development Platform will allow, for the first time, collaborative creation and execution of personalised care plans for multi-morbid patients through systematic and semi-automatic reconciliation of clinical guidelines, with the help of Decision Support Modules for risk prediction and stratification, recommendation reconciliation, poly-pharmacy management and goal setting. Fusion of multimodal patient and provider data will be achieved via C3-Cloud Interoperability Middleware for seamless integration with existing information systems. An Integrated Terminology Server with advanced semantic functions will enable meaningful analysis of multimodal data and clinical rules. Active patient involvement and treatment adherence will be achieved through a Patient Empowerment Platform ensuring patient needs are respected in decision making and taking into account preferences and psychosocial aspects. Co-design and 4-layered multi-method multi-stakeholder evaluation will lead to a user friendly solution. To demonstrate feasibility, pilot studies will focus on diabetes, heart failure, renal failure, depression in different comorbidity combinations. Pilots will operate for 15 months in 3 European regions with diverse health and social care systems and ICT landscape, which will allow for strengthening the evidence base on health outcomes and efficiency gains. C3-Cloud adaptive patient pathways and organisational models validated by patient organisations and a clinical reference group, change management and training guidelines will be shared with the European community. Commercial exploitation of C3-Cloud integrated care solutions will be facilitated through an Industry Vendor Forum and commercial EHR/PHR products of 3 leading SMEs.


Grant
Agency: Cordis | Branch: FP7 | Program: CSA-SA | Phase: HEALTH.2013.4.1-4 | Award Amount: 553.89K | Year: 2013

The landscape of genetic testing is rapidly changing. Soon, whole genome sequence analysis (3Gb-testing) will be an effective and financially viable alternative to targeted gene analysis. New technologies that allow efficient sequencing of a whole human genome in a diagnostic setting will have an enormous impact on diagnostic centres replacing many existing molecular and cytogenetic tests. Patients deserve to benefit from our vastly growing knowledge on functional genomics. 3Gb-testing is the ideal method to bring these benefits to the public. However, it is critical to avoid mistakes with respect to ethics, quality, over or mis-interpretation of data. It is essential that our society is prepared for the change once it is implemented. Hence, current gaps in our knowledge have to be identified and research has to be initiated to bridge these gaps. The 3Gb-TEST project will bring stakeholders together and ensure they are informed with respect to the desirable and undesirable developments. The clinical utility and cost effectiveness of whole genome sequencing needs to be determined as part of a robust health technology assessment process (HTA). Interpretation of sequence data in terms of clinical relevance will pose a challenge to both laboratory and clinical geneticists. Substantial investments may be required and the logistic restructuring of genetic services will need to be addressed. This project aims to prepare Europe for innovations in molecular testing. Quality assessment schemes, HTA and guidelines have to be in place. Healthcare professionals must be aware of the impending change and potential impact on practice. The Consortium will inform the healthcare community and make recommendations to the European Commission, the European Society of Human Genetics, and national organizations relevant to this field. A key output will be a validated roadmap for the implementation of diagnostic genome sequencing in Europe.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH-2009-1.4-1 | Award Amount: 15.92M | Year: 2010

Type 1 diabetes is a serious chronic disease with major health risks and heavy burden on patients and society. It is caused by massive immune-mediated loss of insulin-producing beta cells in the pancreas that can so far not be locally corrected. A cellular allotransplant in the liver can install a new beta cell mass but the size is insufficient and the procedure faces limitations of donor shortage, inaccessibility of the implants, risks of associated immunosuppression. Our consortium of research, clinical and bioindustry teams is focused on overcoming these obstacles and implementing a roadmap for translation to preclinical models and clinical trials. We will pursue three interacting tracks. First, our ability to induce beta cell progenitors and stimulate beta cell proliferation in vivo should lead us to cells and compounds that activate this process in a diabetic pancreas, thus activating endogenous beta cell regeneration. Second, we will produce human beta (progenitor) cells in vitro by derivation from stem cells as well as from reprogrammed autologous cells; their therapeutic potential will be compared to that of primary human beta cells following implantation in rodents using a site that is accessible to modulation and monitoring. Third, we will design an antibody-based therapy for inducing immune tolerance to regenerated beta cells and to a beta cell implant. Efficacy, safety and regulatory criteria will be determined for clinical implementation. Clinical protocols will be prepared by adjusting associated therapy and by adopting an accessible and controlled implant site. Clinical trials will benefit from state-of-the art biologic markers for comparative analysis of the developed forms of beta cell therapy. This program should provide proof of principle for strategies that make beta cell transplantation and beta cell regeneration realistic for large numbers of type 1 diabetic patients, and probably also for some categories of type 2 diabetes.


Grant
Agency: Cordis | Branch: H2020 | Program: ERA-NET-Cofund | Phase: HCO-11-2015 | Award Amount: 20.88M | Year: 2016

The ERA-NET NEURON Cofund will coordinate and align European and international research funding programmes in the area of brain-related diseases and disorders of the nervous system. Key activity is the implementation of an EC co-funded joint transnational call for research proposals. The mission of NEURON is based on the fact that disorders of the brain are the major cause for impaired quality of life, and they are a heavy burden not only for patients, their families and carers, but also a socioeconomic problem for society. By improving collaboration and by implementing a variety of additional activities (such as further joint transnational calls and support of early-career scientists) NEURON Cofund will decrease fragmentation of research programmes and improve the funding situation for neuroscience researchers thereby strengthening the search for novel therapeutic approaches to fight brain disease; NEURON Cofund will also develop and provide concrete plans for (i) expanding data sharing, (ii) promoting common data elements for the establishment of patient registries, and (iii) involving stakeholders and relevant existing initiatives such as patient organizations. The aforementioned challenges will be addressed in a network of 22 funding organizations across 14 European Member and Associated States and Third countries.


Grant
Agency: Cordis | Branch: FP7 | Program: ERC-SG | Phase: ERC-SG-LS7 | Award Amount: 1.50M | Year: 2013

The DOHaD (Developmental Origins of Health and Disease) hypothesis states that, because of developmental plasticity, in utero and early postnatal stressors can increase chronic disease risk in childhood and later. Alterations of epigenetic marks, impacting on gene expression, are one mechanism that could explain such long-term impact. These hypotheses have so far been tested mostly in animals, and little for atmospheric pollutants, for which animal evidence is scarce. We aim to characterize the impact of environmental exposures on childhood health. Our focus is on two families of pollutants with a highly prevalent and controllable exposure in humans: atmospheric pollutants and specific high-volume non-persistent chemicals (Bisphenol A, other phenols and phthalates). These pollutants are archetypal of modern life pollutants challenging environmental health research. We will set up a new type of mother-child cohort with early recruitment in pregnancy, intense follow-up (including geolocalisation of subjects with GPS combined with fine-scale air pollution modelling), personal exposure monitoring, repeated collection of biological samples. Transcriptomic analysis, non-invasive clinical examinations (Doppler and ultrasound imaging, ECG, early postnatal evaluation of lung function) will bring clues regarding target functions. This observational approach in humans will be supplemented by an animal experiment aiming at characterizing the impact of in utero exposure to traffic-related atmospheric pollutants on foetal development and health in adulthood, and characterizing target functions and organs more finely than the human study can allow. E-DOHaD spans over the whole range of environmental health disciplines, with epidemiologic and toxicologic studies being conducted in parallel to ease comparability and results synthesis. E-DOHaD is expected to have far-reaching implications in environmental health research and for public health.


Grant
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: PHC-06-2014 | Award Amount: 2.99M | Year: 2015

Very preterm birth is a principal determinant of motor and cognitive impairment in later life. About 50 000 infants in the EU survive very preterm birth annually and are at much higher risk of cerebral palsy, visual and auditory deficits, impaired cognitive ability, psychiatric disorders and behavioural problems than infants born at term. However, the long term prognosis at initial discharge from hospital for each individual infant is unknown. Follow-up screening and prevention programmes aim to identify health problems early, enable interventions to improve outcome and to allow optimal management of health care. Despite the recognised importance of these programmes, little is known about their actual application and impact. These programmes consume significant resources because of the multidisciplinary staff required for clinical and developmental assessments and interventions, the coordination required to maintain contact with children after discharge and the time input from families. This project uses a unique resource the EPICE cohort of 6675 babies born before 32 weeks of gestational age and surviving to discharge home in 18 geographically diverse regions in 2011/2012 to assess the impact of these screening programmes on health, care and quality of life for very preterm infants and their families as well as on coverage, ability to meet needs, health equity and costs at the population-level. It will also generate new knowledge about assessment tools and methods. Four inter-related studies will be carried out in 11 EU countries by a multi-disciplinary consortium of clinicians (in obstetrics, paediatrics, and child development), researchers (in epidemiology, health services research and health economics) and a user organisation. Partners have the expertise to implement this project and the national and international renown to translate its result into better programmes and policies.


Grant
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: ICT-26-2014 | Award Amount: 3.63M | Year: 2015

Early identification of individuals at risk for CVD allows early intervention to halt or reverse the pathological process. This is the driver of Medtronic and partners to develop a mobile, low-cost, non-invasive, point-of-care screening device for CVD. Assessment of arterial stiffness by measurement of the aortic pulse wave velocity (aPWV) is included in the latest ESC/ESH guidelines for CVD risk prediction. Besides aPWV, early identification of arterial stenosis and cardiac contraction abnormalities can be used to improve CVD risk classification. However, no tools are available today to screen a large population at primary care on these parameters, and individuals that are considered to be at low or moderate risk are too often undiagnosed. The objective of CARDIS is to investigate and demonstrate the concept of a mobile, low-cost device based on a silicon photonics integrated laser Doppler vibrometer and validate the concept for the screening of arterial stiffness, detection of stenosis and heart failure. We will: Investigate, design and fabricate the optical subsystems and components: silicon photonics chip with integrated Ge-detectors, micro-optics, micro-optical laser bench, optical package Integrate the subsystems and build a multi-array laser interferometer system Develop a process flow scalable to high volumes for all sub-systems and their integration steps Investigate and develop the biomechanical model to translate optical signals related to skin-level vibrations into underlying CVD physiological events Validate the system in a clinical setting Photonics integration is needed to enable a device that is mobile (small size, small weight, robust (no moving parts), low cost (high volume scalable process flow) and allows fast screening (laser array). The partners commit to protect IP whenever possible, disseminate results via open access and, if target specs are met, commercially exploit and transfer the technology to create social and economic impact.


Grant
Agency: Cordis | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2012-ITN | Award Amount: 3.76M | Year: 2013

Over the last decade, enormous progress has been made on recording the health state of an individual patient down to the molecular level of gene activity and genomic information even sequencing a patients genome for less than 1000 dollars is no longer an unrealistic goal. However, the ultimate hope to use all this information for personalized medicine, that is to tailor medical treatment to the needs of an individual, remains largely unfulfilled. To turn the vision of personalized medicine into reality, many methodological problems remain to be solved: there is a lack of methods that allow us to gain a causal understanding of the underlying disease mechanisms, including gene-gene and gene-environment interactions. Similarly, there is an urgent need for integration of the heterogeneous patient data currently available, for improved and robust biomarker discovery for disease diagnosis, prognosis and therapy outcome prediction. The field of machine learning, which tries to detect patterns, rules and statistical dependencies in large datasets, has also witnessed dramatic progress over the last decade and has had a profound impact on the Internet. Amongst others, advanced methods for high-dimensional feature selection, causality inference, and data integration have been developed or are topics of current research. These techniques address many of the key methodological challenges that personalized medicine faces today and keep it from rising to the next level. Despite this rich potential of machine learning in personalized medicine, its impact on data-driven medicine remains low, due to a lack of experts with knowledge in both machine learning and in statistical genetics. Our ITN aims to close this gap by bringing together leading European research institutes in Machine Learning and Statistical Genetics, both from the private and public sector, to train 14 early stage researchers.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2010.2.4.1-8 | Award Amount: 7.82M | Year: 2011

Each year more than 63,000 new cases of kidney cancer are diagnosed in the European Union. Approx. 50% of all patients have metastasized renal cell cancer (mRCC) at presentation or develop metastases during follow-up. 5-year relative survival of mRCC has been extremely poor: between 5 and 10%. In the past few years, so-called targeted therapies that suppress angiogenesis have changed the clinical practice for patients with mRCC dramatically. Both response and toxicity to these expensive drugs is, however, extremely variable. With an increasing number of compounds becoming available, choice of compounds and sequence is becoming extraordinary challenging. Classical patient and tumor characteristics appear to have poor predictive ability. The aim of this project is to identify germline genetic markers that predict response and toxicity (by the use of high-resolution whole genome SNP arrays in groups of hundreds of patients treated with different agents), identify expression and epigenetic markers in tumors that predict response (by comparing expression and methylome arrays and kinase profiles in frozen tumor tissue from groups of patients who do (N=30) and do not (N=30) respond to different agents), to integrate these data from different platforms by means of bioinformatics and to conduct focused functional studies on the results in order to improve understanding of the critical molecular and resistance pathways involved. A large European consortium that has recruited and will recruit large numbers of patients ensures that the new markers identified in a first discovery phase can be tested in a subsequent replication phase. We have the ambition to define new validated risk stratification criteria to be used in personalized patient management. These criteria allow prediction of individual therapy response and resistance and will enable the monitoring of successful treatment outcome while reducing unnecessary drug use and expense.


Grant
Agency: Cordis | Branch: H2020 | Program: CSA | Phase: INFRADEV-2-2015 | Award Amount: 1.44M | Year: 2016

ERINHA2 aims to complete the work carried out during the first preparatory phase (PP1) - ERINHA - in order to reach the financial, administrative and technical maturity necessary to complete the establishment of the Research Infrastructre and ensure that the operation phase can begin in 2018. ERINHA2 will therefore finalise the decision to use the status of an association and prepare the necessary legal document to register the RI depending on the country voted on to host the Central Coordinating Unit. ERINHA2 will prepare all procedures and protocols (human resources, IPR, ethics) needed to effectively operate the RI. The financial and business plans prepared in ERINHA (PP1) will updated and presented to national and international stakeholders to obtain their agreement to fund the infrastructure. An overarching group of activities - WP5, Stakeholders and commitment - will aim to accompany all partner countries in their efforts to obtain agreements and funding. This WP5 will ensure all relevant stakeholders and potential users are informed of the progress, services and benefits of ERINHA. The utlimate outcome of ERINHA2 will be the signtature of the ERINHA statutes among the founding countries to officially establish the RI and enter into the construction phase.


Grant
Agency: Cordis | Branch: FP7 | Program: CSA-CA | Phase: HEALTH.2011.3.3-4 | Award Amount: 2.27M | Year: 2011

On the regional level, Europe has one of the highest levels of resources for mental health care. Despite this, the high burden and impact of mental disorders in Europe is expected to rise. ROAdmap for Mental health Research (ROAMER) is designed to develop a comprehensive, consensus-based roadmap to promote and integrate mental health and well-being research in Europe. Research advances and innovations are to be devoted to decreasing the burden of mental disorders and increasing the mental health and well-being of Europeans. ROAMER will combine a neutral, fact-based methodology with extensive stakeholder involvement in consultation and dissemination. During the kick-off phase, the methodology (including comprehensive EU-wide indicators to assess the current state of the art, gaps and advances) and the desired situation (scoping and objectives) will be finalised. Secondly, the current state of the art will be examined, using these tools. In the third phase, the desired situation will be compared with the current situation to identify gaps and advances. Phase four prioritises these gaps and advances, as well as solutions. In the fifth phase, this information is translated into roadmaps covering infrastructures, capacity building and funding strategies for scientific areas relevant to mental health and well-being: biomedical, psychological, social, economic and public health. Geographical, interdisciplinary, developmental, gender and age perspectives will be taken into account. To achieve consensus among a broad group of scientists, service users, carers, government and funding institutions and other stakeholders, ROAMER uses web-based surveys, scientific workshops, scientific advisory board meetings, stakeholder meetings, consensus meetings, and policy meetings. The consortium consists of leading experts in the field, and is well balanced in terms of geographical distribution and complementary expertises across all relevant aspects of mental health research.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.1.4-1 | Award Amount: 7.82M | Year: 2013

This project will tackle the huge complexity of taking stem cell therapies to clinical application for neurodegenerative disease by focusing on selective differentiation of a single neuronal phenotype (medium spiny striatal neuron: MSN) for a single well-defined disease (Huntingtons: HD). Our consortium contains expertise in all elements required to drive this technology to the point of clinical delivery, including expertise in stem cell differentiation and control of proliferation; in vitro genetic, molecular, cellular and functional characterisation; preclinical assessment in both rodents and primates models of HD; GMP knowledge, development and production; and clinical translation. Our clinical team includes world leaders in HD clinical trials, including fetal neural transplants and is well placed to design the translation process. We focus on human embryonic stem (hES) cells as our primary target for first-in-man proof-of-concept studies, as they are closest to clinical readiness. HD is the target disease as it provides both an excellent model relevant to a wide range of neurodegenerative conditions, and is a stringent test of the capacity of selectively differentiated stem cells to repair neural circuits. The starting point for the work is the existence within the consortium of three of the most advanced protocols to date for MSN differentiation, and a feature of our consortium is that the specificity of stem cell differentiation will be tested against primary fetal MSNs (current gold standard) at all stages of both in vitro and in vivo assessment. In order to maintain flexibility in an emerging ethical environment, we will develop induced pluripotent (hiPS) cells to the point of GMP validation as a second generation target to hESCs. This will build European infrastructure and capacity to deliver emergent stem cell therapies through the highest quality clinical trials into clinical practice in a broad range of human neurodegenerative diseases.


Grant
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: INFRAIA-1-2014-2015 | Award Amount: 12.17M | Year: 2015

The overall objective will be to create and mobilise an International network of high calibre centres around a strong European group of institutes selected for their appropriate expertises, to collect, amplify, characterise, standardise, authenticate, distribute and track, mammalian and other exotic viruses. The network of EVAg laboratories including 25 institutions represents an extensive range of virological disciplines. The architecture of the consortium is based on the association of capacities accessible to the partners but also to any end-users through the EVAg web-based catalogue. This concept has been elaborated and tested for its efficiency during the successful EVA project (FP7). The project will integrate more facilities dedicated to high risk pathogen (HRP) manipulation (1 in EVA, 13 in EVAg) The access to products derived from those HRP will be enhanced and for instance the production of diagnostic reagents will be facilitated. The new project will also provide access to high containment biosafety facilities to carry out in vivo studies of infectious disease using natural or models hosts, to look at prophylactic or therapeutic control measures and to develop materials for the evaluation of diagnostic tests, meaning an extensive capacity to service and to training. EVAg will also link up with other network-based virus-associated programmes that exist globally. However, looking further ahead, EVAg is conceived ultimately to be an open entity aiming at developing synergies and complementarity capabilities in such a way as to offer an improved access to researchers. This project will generate the largest collection of mammalian viruses in the world and move beyond the current state-of-the-art to provide an increasingly valuable resource and service to the worlds scientific community, including government health departments, higher education institutes, industry and, through information systems, the general public.


Grant
Agency: Cordis | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2014-ETN | Award Amount: 3.23M | Year: 2015

Demand for highly trained scientists with a deep understanding of wave propagation in complex media, and capable of exploiting this knowledge to develop imaging tools for seismology and acoustics, is very high in the Earth and environmental sciences. Wave-based imaging serves to map spatial and temporal variations in the structure of the Earths interior, of the oceans and atmosphere; it is used to monitor faults and volcanoes and detect natural-resource reservoirs. It is relevant to other disciplines, medical imaging being one of its most widespread applications. Todays Earth scientists are faced with a set of questions that require the application of wave-based imaging at unprecedented resolution. WAVES aims at fostering scientific and technological advances in this context, stimulating knowledge exchange between seismologists and acousticians, and researchers in the public/private domains. A unique strength of our network resides in the participation of novel physical acoustics laboratories, managed by beneficiaries/partners of WAVES, with a strong record of experimental research on inter-disciplinary and seismology-related topics. WAVES will train young scientists working in academia or industry in how to use this resource effectively, re-introducing the laboratory into the ideas-to-applications pipeline. Experimental work will serve to develop new theory, addressing topics of current interest such as acoustic time-reversal, scattering-based imaging. A truly multidisciplinary network, WAVES will apply these new ideas in a number of contexts: medical elastography is used as a tool to implement novel analogue models of seismic faults; wave sources are localized by a bio-inspired system making use of very few receivers, etc. Through WAVES, a critical mass of expertise will consolidate, defining the study of acoustic/elastic wave propagation and wave-based imaging/monitoring as an independent discipline, rich in applications of intellectual and societal relevance.


Grant
Agency: Cordis | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2014-ETN | Award Amount: 4.00M | Year: 2015

Metabolism is the foundation of all living organisms. While cells in a population are often phenotypically different, most of our current analytical approaches still probe metabolism only at the population level. Because strong evidence exists that metabolic cell-to-cell heterogeneity has, for instance, disease relevance, researcher from MetaRNA will overcome this severe analytical limitation through exploiting exciting opportunities emerging from the RNA field. Such synergy potential between the metabolism and RNA research fields has until today not been exploited, because they are separated from each other in Europe and worldwide. Through consequently missing research training programs we thus lack experts with combined knowledge in metabolism and RNA. The aim of the MetaRNA proposal is therefore to establish a European Training Network (ETN) that educates specialists for academia and industry - fully trained at the interface of these two fields - in the development and application of RNA-based sensors to investigate metabolism at the single-cell level, to apply these tools for novel biotechnological applications and to provide a framework for their future use in diagnostics and therapeutics. In MetaRNA, eight research groups from the metabolic and RNA fields and six partners from the private sector join forces to create a platform of mobility and training to 15 early-stage researchers (ESRs), by means of customized research projects, exchange of knowhow among researchers and partners, attendance to specialized courses, workshops and conferences, as well as training in complementary skills.


Grant
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: PHC-22-2015 | Award Amount: 5.74M | Year: 2016

Major depressive disorder, dementia, anxiety disorders, and substance abuse affect a substantial part of the European older population. Over 70% of Europeans reside in cities, and this percentage will increase in the next decades. Urbanization and ageing have enormous implications for public mental health. Cities pose major challenges for older citizens, but also offer opportunities for the design of policies, clinical and public health interventions that promote mental health. The overall aim of the MINDMAP project is to identify the opportunities offered by the urban environment for the promotion of mental wellbeing and cognitive function of older individuals in Europe. The project will advance understanding by bringing together longitudinal studies across cities in Europe, the US and Canada to unravel the causal pathways and multi-level interactions between the urban environment and the social, behavioural, psychosocial and biological determinants of mental health and cognitive function in older adults. Specifically, the project will (a) assess the impact of the urban environment on the mental wellbeing and disorders associated with ageing, and estimate the extent to which exposure to specific urban environmental factors and policies explain differences in ageing-related mental and cognitive disorders both within as well as between European cities, (b) assess the causal pathways and interactions between the urban environment and the individual determinants of mental health and cognitive ageing in older adults, (c) use agent-based modelling to simulate the effect of urban environmental, prevention and care policies on the trajectories of mental health and cognitive ageing across cities in Europe. Knowledge will significantly contribute to future-proof preventive strategies in urban settings favouring the mental dimension of healthy ageing, the reduction of the negative impact of mental disorders on co-morbidities, and maintaining cognitive ability in old age.


Grant
Agency: Cordis | Branch: H2020 | Program: CSA | Phase: PHC-34-2014 | Award Amount: 939.72K | Year: 2015

ASSESS CT will contribute to better semantic interoperability of eHealth services in Europe, in order to optimise care and to minimise harm in delivery of care. In a joint one-year effort, the ASSESS CT consortium will investigate the fitness of the clinical terminology SNOMED CT as a potential standard for EU-wide eHealth deployments, scrutinising clinical, technical, financial, and organisational aspects. Unbiased towards SNOMED CT adoption, the ASSESS CT project will employ established evaluation approaches from social science. It will scrutinise adoption against two alternative scenarios: to abstain from actions at the EU level, or to devise an EU-wide semantic interoperability framework without SNOMED CT. ASSESS CT will review the current state of SNOMED CT through survey and focus group, regarding its use by IHTSDO members and the fulfilment of semantic interoperability use cases, the relationship with EU-wide recommendations, known technical and organisational drawbacks, and maintenance of the terminology. A series of studies using sampled clinical data will provide new evidence about conceptual and term coverage for selected languages, as well as technical fitness in manual and automated semantic annotation scenarios. The consortium will also analyse the impact of SNOMED CT adoption from a socio-economic viewpoint, encompassing management, business, organisational, and governance aspects. Validation of all working tasks, both political and domain-specific, will be secured through four large workshops with a list of distinguished experts assembled in an Expert Panel, Committee of MS Representatives, and national focus groups. Sufficient budget is reserved, also for coordination across the parallel H2020 Call PHC34 projects. Concrete strategy recommendations will be delivered to both MS, the EC, and SDOs about how SNOMED CT can scale up successful adoption and contribute to building a EU eHealth Interoperability Framework.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2012.2.1.2-2 | Award Amount: 23.12M | Year: 2012

METACARDIS applies a systems medicine multilevel approach to identify biological relationships between gut microbiota, assessed by metagenomics, and host genome expression regulation, which will improve understanding and innovative care of cardiometabolic diseases (CMD) and their comorbidities. CMD comprise metabolic (obesity, diabetes) and heart diseases characterized by a chronic evolution in ageing populations and costly treatments. Therapies require novel integrated approaches taking into account CMD natural evolution. METACARDIS associates European leaders in metagenomics, who have been successful in establishing the structure of the human microbiome as part of the EU FP7 MetaHIT consortium, clinical and fundamental researchers, SME, patients associations and food companies to improve the understanding of pathophysiological mechanisms, prognosis and diagnosis of CMD. We will use next-generation sequencing technologies and high throughput metabolomic platforms to identify gut microbiota- and metabolomic-derived biomarkers and targets associated with CMD risks. The pathophysiological role of these markers will be tested in both preclinical models and replication cohorts allowing the study of CMD progression in patients collected in three European clinical centres of excellence. Their impact on host gene transcription will be characterised in patients selected for typical features of CMD evolution. Application of computational models and visualisation tools to complex datasets combining clinical information, environmental patterns and gut microbiome, metabolome and transcriptome data is a central integrating component in the research, which will be driven by world leaders in metagenomic and functional genomic data analysis. These studies will identify novel molecular targets, biomarkers and predictors of CMD progression, paving the way for personalized medicine in CMD.


Grant
Agency: Cordis | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2016 | Award Amount: 3.20M | Year: 2017

FOIE GRAS provides innovative training for 13 early stage researchers (ESRs) to answer two critical and unanswered questions: a) Is hepatic bioenergetic remodelling involved in NAFLD pathogenesis, and target for stratification or therapeutic/lifestyle interventions? and b) Is the disruption of the gut-liver axis involved in NAFLD progression? In Western Societies, there has been a recent surge of non-alcoholic fatty liver disease (NAFLD). Its progression to nonalcoholic steatohepatitis (NASH) is a leading risk factor for development of Type 2 diabetes, cirrhosis, and hepatocellular carcinoma. FOIE GRAS is first in supporting a cohesive and synergistic intersection of complementary and interdisciplinary training skills from academic and non-academic partners. FOIE GRAS combines strong scientific expertise with integrated and complementary training in translational research, clinical practice, technology commercialization, and public outreach, the combination of which in targeting NAFLD is lacking in the EU. Industrial partners CETICS, Mediagnost and Seahorse Biosciences provide experience on technology commercialization alongside scientific contributions while the affiliated patient organization will contribute with important training in societal awareness topics. ESRs training will utilize network-wide workshops and secondments to foster translation of basic research to clinical applications and SME creation. This diverse yet integrated skill set enhances the employment prospects of the trained researchers in both academic and non-academic sectors. Researchers will be endowed with excellent basic scientific knowledge and timely technology transfer know-how for developing novel therapeutic approaches for reversing the burden of NAFLD, thereby advancing both health and economic well-being of European citizens and approaching NAFLD research in the EU from its counterparts in the US and Asia.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2011.1.4-2 | Award Amount: 7.68M | Year: 2011

Transplantation of donor hepatocytes has become an alternative to liver transplantation for the treatment of liver diseases. However, in addition to the complication imposed by severe shortage of donor livers, adult hepatocytes cannot be expanded in vitro. Autologous transplantation of genetically corrected hepatocytes represents another strategy as it circumvents the need for immunosuppression but this approach requires removal of 20% of the liver to isolate hepatocytes, which is not devoid of risks in patients with metabolic diseases. Therefore, there is a critical need to explore the potential human stem cells such as human Embryonic Stem (hES) cells to generate sufficient quantities of functional human hepatocytes. However, the production of safe and fully functional, human hepatocytes from hES cells under GMP conditions for clinical applications remains to be achieved. The general scientific objectives of this proposal are: - to develop scale-up procedures for hES cells and to produce GMP-grade tissue culture reagents that will facilitate large-scale differentiation of hES cells to hepatocytes. InnovaLiv aims to provide the EU healthcare system with a renewable and reliable source of functional clinical-grade hepatocytes generated from EU hES cells lines. Rigorous standards to ensure the safety and quality of these cells will be developed. The GMP-compliant hepatocytes will be prepared as a prototype therapy aiming at treating one patient on the basis of a compasive use protocol. - to provide proof-of-principle that defective hepatic function associated with inherited disorders (Familial Hypercholesterolemia, Hemophilia B, Crigler-Najjar) can be regenerated by correction of the deficiency in patient-specific iPS cells using integration-targeted lentiviral vectors to express the therapeutic cDNAs. Commercialization of novel products such as GMP-grade cells and cell culture tools will be performed by two partner SMEs that will assume leading roles in InnovaLiv.


Grant
Agency: Cordis | Branch: FP7 | Program: CP | Phase: ICT-2009.5.2 | Award Amount: 9.76M | Year: 2010

TRANSFoRm will develop rigorous, generic methods for the integration of Primary Care clinical and research activities, to support patient safety and clinical research via:\n1.\tRich capture of clinical data, including symptoms and signs rather than just a single diagnosis. A generic, dynamic interface, integrated with electronic health records (EHR), will facilitate both diagnostic decision support and identification of patients eligible for research, thus enhancing patient safety.\n2.\tDistributed interoperability of EHR data and other data sources that maintains provenance, confidentiality and security. This will enable large-scale phenotype-genotype association studies and follow up of trials.\n3.\tSoftware tools and services to enable use of controlled vocabulary and standardised data elements in clinical research. This will enable integration and reuse of clinical data.\nWhy this is important? Whilst diagnostic error is the commonest cause of litigation in Primary Care, EHR systems do not provide for easy collection of the data required for decision support. At the same time, clinical research is becoming uneconomic due to the costs of recruiting and following study participants, tasks that could be supported by the use of data from EHRs.\nWho will conduct the work? A multi-disciplinary consortium of ICT and clinical researchers from across Europe. These include experts in ontology, integration, distributed systems, security, data mining, user-facing design, evaluation and clinical research domains. Clinical participants include The European Clinical Research Infrastructures Network (where the systems will be deployed), The European General Practice Research Network, and a major Contract Research Organisation.\nWhat is the anticipated impact? Improved patient safety by speeding translational research, quicker and more economic recruitment and follow up of RCTs, and enhanced uptake of eHR systems that offer support for clinical care and research.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-CSA-Infra | Phase: INFRA-2011-1.1.5. | Award Amount: 10.83M | Year: 2012

ECRIN is a distributed ESFRI-roadmap pan-European infrastructure designed to support multinational clinical research, making Europe a single area for clinical studies, taking advantage of its population size to access patients. Servicing multinational trials started during its preparatory phase, and it now applies for an ERIC status by 2011. The ERIC budget will be restricted to core activities required to enable provision of services, and the ECRIN-IA project is designed to expand ECRIN partnerships and impact beyond this core activity. Networking activities will promote pan-European expansion, capacity building, and partnership with other world regions, and address the funding issue (WP2). ECRIN-IA will develop e-services, education material to train professionals and patients associations, and communication with users, patients, citizens and policymakers (WP3). It will support the structuring and connection to ECRIN of disease-, technology-, or product-oriented investigation networks and hubs focusing on specific areas: rare diseases (WP4), medical device (WP5), nutrition (WP6). Transnational access activities will support the cost of multinational extension of clinical trials on rare diseases, medical device and nutrition selected by the ECRIN scientific board (WP7). Joint research activities are designed to improve the efficiency of ECRIN services, through the development of tools for risk-adapted monitoring (WP8), and the upgrade of the VISTA data management tool (WP9). This project will build a consistent organisation for clinical research in Europe, with ECRIN developing generic tools and providing generic services to multinational studies, and supporting the construction of pan-European disease-oriented networks, that will in turn act as ECRIN users and provide the scientific content. Such organisation will improve Europes attractiveness for industry trials, boost its scientific competitiveness, and result in better healthcare for European citizens.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2010.2.4.5-1 | Award Amount: 15.66M | Year: 2010

Causes explaining the epidemic of IgE-associated (allergic) diseases are unclear. MeDALL (Mechanisms of the Development of Allergy) aims at generating novel knowledge on mechanisms of allergy initiation, in particular in childhood. To understand how a complex network of genetic and environmental factors leads to complex allergic phenotypes, a novel stepwise, large and integrative translational approach is needed. MeDALL includes experts in allergy, epidemiology, genetics, immunology, biology, animal models, biochemistry and systems biology combining strengths of ongoing EU projects. Classical phenotypes (expert-based) and novel phenotypes of allergy (hypothesis-free statistical modelling) are compared. Population-based data are collected from a cross-sectional study (Karelia) and existing birth-cohorts followed using a common protocol. IgE to foods and inhalants are tested using component-resolved diagnosis across Europe in populations. Biomarker profiles (fingerprints) are extensively assessed using epigenetics, targeted proteomics and unbiased transcriptomics in a subsample of the study population. Those associated with allergic phenotypes are validated in large study populations. Relevant fingerprints are combined into network biomarker phenotype handprints using a systems biology approach and validated in a sufficiently powered sample. Animal studies and in vitro human immunology reinforce the validation. This information coupled with classical and novel phenotypes characterize environmental protective and susceptibility factors of allergy and risk groups. Results are fitted into new integrative complex mathematical models to establish suitable biomarkers for early diagnosis, prevention and targets for therapy of allergy-associated diseases such as asthma and atopic dermatitis. Ethics and gender are considered. MeDALL aims at improving health of European citizens, Europe competitiveness and innovative capacity while addressing global health issues.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2009-4.2-1 | Award Amount: 7.67M | Year: 2010

Previous studies have demonstrated the high frequency of bacterial sepsis in neonates and infants admitted to neonatal intensive care unit (NICU), often associated with serious complications or death. Many pathogens capable of causing nosocomial bacterial sepsis in neonates and young infants have developed resistance to the antibiotics considered of choice for treatment. Meropenem is an antibiotic that can overcome antimicrobial resistance, generally being safe and well tolerated with very good pharmacokinetic (PK) and pharmacodynamic characteristics. However, it has not yet been registered in neonates and infants aged <3 months due to limited data on its PK characteristics, activity and safety. Core objectives of NeoMero are to evaluate the PK, safety and efficacy of meropenem in comparison to standard care in neonates and infants aged <3 months suffering from late-onset sepsis and describe PK and safety in bacterial meningitis (BM). To achieve these aims, clinical trials on meropenem use for late-onset sepsis and BM will be developed. Using previously published PK models, a sampling scheme will be designed and population PK analysis used to identify relevant PK parameters. Safety will be evaluated through analysis of haematological and biochemical parameters and monitoring adverse events. Appearance of resistant bacteria will be monitored through regular cultures during therapy. Clinical assessments including neurological and developmental evaluations (Bayley Scales) will be conducted during two years after enrolment. Immunologic and genetic studies will also be performed to evaluate predictors of susceptibility to infections and response to therapy. In addition, resistant bacterial isolates will be studied to elucidate the mechanism of resistance and sensitive PCR assays will be used to test culture negative samples. A Paediatric Investigators Plan will be developed and submitted to the EMEA. The results of this study will then be used to develop a PUMA.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2010.4.2-9-1 | Award Amount: 9.40M | Year: 2011

In the development of products for use by humans it is vital to identify compounds with toxic properties at an early stage of their development, to avoid spending time and resource on unsuitable and potentially unsafe candidate products. Human pluripotent stem cell lines offer a unique opportunity to develop a wide variety of human cell-based test systems because they may be expanded indefinitely and triggered to differentiate into any cell type. SCR&Tox aims at making use of these two attributes to provide in vitro assays for predicting toxicity of pharmaceutical compounds and cosmetic ingredients. The consortium has been designed to address all issues related with biological and technological resources to meet that goal. In order to demonstrate the value of pluripotent stem cells for toxicology, the consortium will focus on four complementary aspects: Relevance i.e. establishing and maintaining discrete cell phenotypes over long-term cultures; providing large versatility to adapt to assays of specific pathways. Efficiency for i) automated cell production and differentiation, ii) cell engineering for differentiation and selection iii) multi-parametric toxicology using functional genomic, proteomic and bioelectronics. Extension i.e. i) scalability through production of cells and technologies for industrial-scale assays, and ii) diversity of phenotypes (5 different tissues), and of genotypes (over 30 different donors). Normalization validation and demonstration of reproducibility and robustness of cell-based assays on industrial-scale platforms, to allow for secondary development in the pharmaceutical and cosmetic industry. SCR&Tox will be intricately associated to other consortia of the Alternative Testing call, sharing biological, technological and methodological resources. Proof of concept of the proposed pluripotent stem cell-based assays for toxicology will be provided on the basis of toxicity pathways and test compounds identified by other consortia.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP-SICA | Phase: HEALTH-2009-4.3.1-3 | Award Amount: 13.73M | Year: 2010

Worm infections are receiving increased attention due to: the wide geographic overlap in occurrence between worms and HIV, TB and malaria; the large proportion of individuals (minimal estimates around 25%) co-infected with worms and HIV/TB/ malaria; the potential risk of increasing disease burden; the very limited understanding of the impact by worm infections on HIV-, TB- and malaria-specific immune responses and on their clinical outcome; the lack of established intervention guidelines for treatment of worm infections; and the scarce information on the impact by worm infections on vaccination and vaccine-induced immune responses. In order to address these complex and challenging scientific issues, IDEA project will focus its efforts on four primary objectives: a) the worm-induced modulation of the functional and molecular profile of HIV-, TB- and malaria-specific immune responses, b) the impact by worm co-infections on measures of disease activity of PRDs, c) the immunologic markers of worm-, HIV-, TB- and malaria-specific immune responses associated with better control of pathogen replication and disease, and d) the modulation by worm co-infections of vaccine-induced immune responses. To achieve these objectives, IDEA project has developed a global and innovative strategy which includes: a) the alliance between African and European leading scientists in the field of worms, HIV, TB and malaria, b) the multidisciplinary expertise involving immunologists, parasitologists, epidemiologists, clinicians, and experts in vaccines, c) cutting edge immunology and the most innovative technologies to profile immune response, d) the access to large cohort studies bringing a number of centres working on worms and PRDs in Africa together, and e) the access to experimental HIV, TB and malaria vaccine candidates under clinical development in Africa.


Patent
French National Institute for Agricultural Research, French Institute of Health and Medical Research | Date: 2015-01-28

The present invention relates to a vector useful for the production and secretion of a substance of interest by bacteria and applications thereof.


Patent
University of Rennes 1, French National Institute for Agricultural Research, French Institute of Health and Medical Research | Date: 2012-11-16

The present invention relates to a recombinant vector for expressing and secreting, by a propionibacterium, at least one eukaryotic peptide or protein of interest, comprising at least: The invention further relates to the uses of such a vector in the pharmaceutical field or for the large-scale production of peptides or proteins of interest.


Patent
French Institute of Health, Medical Research, University Paris - Sud and French National Institute for Agricultural Research | Date: 2012-06-15

The present invention relates to methods and pharmaceutical compositions for treating cancer. More specifically, the invention relates to a polypeptide isolated from Brevibacterium aurantiacum that shows methionine gamma-lyase and homocysteinase activities. The present invention also relates to the use of such a polypeptide for the treatment of cancer.


Grant
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: SC1-PM-04-2016 | Award Amount: 10.41M | Year: 2017

Early life is an important window of opportunity to improve health across the full lifecycle. European pregnancy and child cohort studies together offer an unique opportunity to identify a wide range of early life stressors linked with individual biological, developmental and health trajectory variations, and to the onset and evolution of non-communicable diseases. LIFECYCLE will establish the EuroCHILD Cohort Network, which brings together existing, successful pregnancy and child cohorts and biobanks, by developing a governance structure taking account of national and European ethical, legal and societal implications, a shared data-management platform and data-harmonization strategies. LIFECYCLE will enrich this EuroCHILD Cohort Network by generating new integrated data on early life stressors related to socio-economic, migration, urban environment and life-style determinants, and will capitalize on these data by performing hypothesis-driven research on early life stressors influencing cardio-metabolic, respiratory and mental health trajectories during the full lifecycle, and the underlying epigenetic mechanisms. LIFECYCLE will translate these results into recommendations for targeted strategies and personalized prediction models to improve health trajectories for current and future Europeans generations by optimizing their earliest phase of life. To strengthen this long-term collaboration, LIFECYCLE will organize yearly international meetings open to pregnancy and child cohort researchers, introduce a Fellowship Training Programme for exchange of junior researchers between European pregnancy or child cohorts, and develop e-learning modules for researchers performing life-course health studies. Ultimately, LIFECYCLE will lead to a unique sustainable EuroCHILD Cohort Network, and provide recommendations for targeted prevention strategies by identification of novel markers of early life stressors related to health trajectories throughout the lifecycle.


Grant
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: PHC-11-2015 | Award Amount: 7.42M | Year: 2016

Cancer is the second leading cause of mortality in EU member states with ~90% of all cancer deaths caused by metastatic spread. Despite its significance, measuring metastatic potential as well as potential indicators of therapy efficacy remain unmet clinical challenges. Recently, it has been demonstrated in vitro, that aggressive metastatic cells pull on their surroundings suggesting that metastatic potential could be gauged by measuring the forces exert by tumours. Furthermore, many solid tumours show a significantly increased interstitial fluid pressure (IFP) which prevents the efficient uptake of therapeutic agents. As a result, a reduction in IFP is recognized as a hallmark of therapeutic efficacy. Currently, there is no non-invasive modality that can directly image these forces in vivo. Our objective is the non-invasive measurement of both IFP within tumours as well as the forces they exert on their surrounding environment. This will be used to predict a tumours metastatic potential and importantly, changes in these forces will be used to predict the therapeutic efficacy of drug therapy. To attain this goal, the biomechanical properties of the tumour and its neighbouring tissue will be measured via MR-elastography at various measured deformation states. Resultant images will be used to reconstruct images of the internal and external forces acting on the tumour. We call this novel imaging modality Magnetic Resonance Force (MRF) imaging. We will calibrate MRF via cell cultures and pre-clinical models, and then test the method in breast, liver, and brain cancer patients. Thereby, we will investigate whether MRF data can predict metastatic spread and measure IFP in patients. We will also investigate the potential to non-invasively modulate the force environment of cancer cells via externally applied shear forces with the aim of impacting cell motility and proliferation. This can provide novel mechanism for anticancer therapeutic agents via mechanotransduction.


Grant
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: PHC-30-2015 | Award Amount: 3.34M | Year: 2016

Breast cancer is the most common type of cancer affecting woman in the EU. Multidisciplinary Breast Units (BUs) were introduced in order to deal efficiently with breast cancer cases, setting guideline-based quality procedures and a high standard of care. However, daily practice in the BUs is hampered by the complexity of the disease, the vast amount of patient and disease data available in the digital era, the difficulty in coordination, the pressure exerted by the system and the difficulty in deciding on cases that guidelines do not reflect. DESIREE aims to alleviate this situation by providing a web-based software ecosystem for the personalized, collaborative and multidisciplinary management of primary breast cancer (PBC) by specialized BUs. Decision support will be provided on the available therapy options by incorporating experience from previous cases and outcomes into an evolving knowledge model, going beyond the limitations of the few existing guideline-based decision support systems (DSS). Patient cases will be represented by a novel digital breast cancer patient (DBCP) data model, incorporating variables relevant for decision and novel sources of information and biomarkers of diagnostic and prognostic value, providing a holistic view of the patient presented to the BU through specialized visual exploratory interfaces. The influence of new variables and biomarkers in current and previous cases will be explored by a set of data mining and visual analytics tools, leveraging large amounts of retrospective data. Iintuitive web-based tools for multi-modality image analysis and fusion will be developed, providing advanced imaging biomarkers for breast and tumor characterization. Finally, a predictive tool for breast conservative therapy will be incorporated, based on a multi-scale physiological model, allowing to predict the aesthetic outcome of the intervention and the healing process, with important clinical and psychological implications for the patients.


Grant
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: PHC-02-2015 | Award Amount: 5.50M | Year: 2016

EuroPOND will develop a data-driven statistical and computational modeling framework for neurological disease progression. This will enable major advances in differential and personalized diagnosis, prognosis, monitoring, and treatment and care decisions, positioning Europe as world leaders in one of the biggest societal challenges of 21st century healthcare. The inherent complexity of neurological disease, the overlap of symptoms and pathologies, and the high comorbidity rate suggests a systems medicine approach, which matches the specific challenge of this call. We take a uniquely holistic approach that, in the spirit of systems medicine, integrates a variety of clinical and biomedical research data including risk factors, biomarkers, and interactions. Our consortium has a multidisciplinary balance of essential expertise in mathematical/statistical/computational modelling; clinical, biomedical and epidemiological expertise; and access to a diverse range of datasets for sporadic and well-phenotyped disease types. The project will devise and implement, as open-source software tools, advanced statistical and computational techniques for reconstructing long-term temporal evolution of disease markers from cross-sectional or short-term longitudinal data. We will apply the techniques to generate new and uniquely detailed pictures of a range of important diseases. This will support the development of new evidence-based treatments in Europe through deeper disease understanding, better patient stratification for clinical trials, and improved accuracy of diagnosis and prognosis. For example, Alzheimers disease alone costs European citizens around 200B every year in care and loss of productivity. No disease modifying treatments are yet available. Clinical trials repeatedly fail because disease heterogeneity prevents bulk response. Our models enable fine stratification into phenotypes enabling more focussed analysis to identify subgroups that respond to putative treatments.


Grant
Agency: Cordis | Branch: H2020 | Program: CSA | Phase: SC1-HCO-02-2016 | Award Amount: 2.08M | Year: 2017

Molecular in vitro diagnostics and biomedical research have allowed great progress in personalised medicine but further progress is limited by insufficient guidelines for pre-analytical workflow steps (sample collection, preservation, storage, transport, processing etc.) as well as by insufficient quality assurance of diagnostic practice. This allows using compromised patients samples with post collection changes in cellular and extra-cellular biomolecules profiles thus often making diagnostic test results unreliable or even impossible. To tackle this, SPIDA4P aims to generate and implement a comprehensive portfolio of 22 pan-European pre-analytical CEN/Technical Specifications and ISO/International Standards, addressing the important pre-analytical workflows applied to personalized medicine. These will also applicable to biomarker discovery, development and validation as well as to biobanks. Corresponding External Quality Assurance (EQA) Schemes will be developed and implemented as well, aiming to survey the resulting quality of samples and diagnostic practice. SPIDIA4P will ensure stakeholder organisations involvements as well as training, education, and counselling as additional major foci of the project. The consortium will closely coordinate with large European public research consortia to obtain access to research and validation studies data serving as evidence for the new standards developments and achieved improvements of diagnosis, patient stratification and prognosis of disease outcome. At this crucial moment in the development of personalised medicine, SPIDIA4P proposes a coordination and support action that reunites 19 highly experienced partners in international standardisation for in vitro diagnostics, coming from private industry including SMEs, public institutions and from one official European Standards Organisation. This strong consortium is balanced and empowered to maximise the impacts of in vitro diagnostics on personalised medicine.


Grant
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: SC1-PM-06-2016 | Award Amount: 6.00M | Year: 2017

Natural epidemics and outbreaks of emerging viral epidemics are growing problems internationally. The general aim of the CCHFVaccine project is to develop and deliver a vaccine, which can significantly increase our capacity to control the situation of Crimean Congo Haemorrhagic fever (CCHF) disease on a global basis. The proposed work program on CCHF virus aims to build a multidisciplinary research network, able to deliver vaccine candidates, methods and procedures eligible for clinical trials, with a special focus on prevention. Thanks to the background, unique facilities and tools available among the consortium participants, CCHFVaccine will deliver tools for countering the threat of this infection in Europe and endemic areas of the world. This work program will attempt to fill gaps in CCHFV virus research on immunology and vaccinology. To achieve this overall aim, an intensive work plan will be put in place with the following specific objectives: i) to produce vaccine candidates, ii) to bring several unique animal models into front line vaccine research, iii) to validate and bring the most promising vaccine candidates to clinical trials, iv) to ensure that an immune mediated protection is adequately understood, v) to perform clinical trials at Phase I and ensure a strategy for the effective deployment and utilization in resource-poor countries, and vi) to link this project to public health bodies, NGOs and vaccine companies. The proposed CCHFVaccine project will succeed in bringing together selected competitive advantages such as: operating capacity with appropriate facilities (state-of-the-art BSL-4s) and the only animal BSL-4 -with capacity to challenge domestic animals in Europe, highly experienced researchers in the development and evaluation of vaccine candidates, authorities and entities of human and animal health, clinical samples from endemic countries, and an international network proven to be functional by the previous EU-funded CCHFever and EDENext.


Grant
Agency: Cordis | Branch: H2020 | Program: COFUND-EJP | Phase: SC1-PM-05-2016 | Award Amount: 74.06M | Year: 2017

The overarching goal of the European Human Biomonitoring Initiative (HBM4EU) is to generate knowledge to inform the safe management of chemicals and so protect human health. We will use human biomonitoring to understand human exposure to chemicals and resulting health impacts and will communicate with policy makers to ensure that our results are exploited in the design of new chemicals policies and the evaluation of existing measures. Key objectives include: Harmonizing procedures for human biomonitoring across 26 countries, to provide policy makers with comparable data on human internal exposure to chemicals and mixtures of chemicals at EU level; Linking data on internal exposure to chemicals to aggregate external exposure and identifying exposure pathways and upstream sources. Information on exposure pathways is critical to the design of targeted policy measures to reduce exposure; Generating scientific evidence on the causal links between human exposure to chemicals and negative health outcomes; and Adapting chemical risk assessment methodologies to use human biomonitoring data and account for the contribution of multiple external exposure pathways to the total chemical body burden. We will achieve these objectives by harmonizing human biomonitoring initiatives in 26 countries, drawing on existing expertise and building new capacities. By establishing National Hubs in each country to coordinate activities, we will create a robust Human Biomonitoring Platform at European level. This initiative contributes directly to the improvement of health and well-being for all age groups, by investigating how exposure to chemicals affects the health of different groups, such as children, pregnant women, foetuses and workers. We will also investigate how factor such as behavior, lifestyle and socio-economic status influence internal exposure to chemicals across the EU population. This knowledge will support policy action to reduce chemical exposure and protect health.


Patent
French Institute of Health, Medical Research, French National Institute for Agricultural Research and University Paris Diderot | Date: 2014-09-18

The present invention relates to the general field of therapy of Inflammatory Bowel Disease (IBD) and/or Irritable Bowel Syndrome (IBS). Thus, the invention relates to a molecule selected from the trappin-2 protein or an active fraction thereof, a member of the WAP family proteins or an active fraction thereof or a member of the Serpin family proteins or an active fraction thereof for the treatment of Irritable Bowel Syndrome (IBS). The invention also relates to a recombinant food-grade bacterium comprising a gene selected from a gene coding for the trappin-2 protein or an active fraction thereof, a gene coding for a member of the WAP family proteins or an active fraction thereof, or a gene coding for a member of the Serpin family proteins or an active fraction thereof.


Patent
National University of Singapore, Institute Pasteur Of Lille, French Institute of Health and Medical Research | Date: 2012-11-02

Described herein are compositions, vaccines, and methods that include use of a mutated Bordetella strain against allergic diseases such as asthma and skin inflammation. Also described are kits. Other compositions, vaccines, and methods are also described.


Patent
Lille 2 University of Health, Law, French Institute of Health, Medical Research, French National Center for Scientific Research and Lille University Hospital Center | Date: 2013-02-06

The present invention relates to a product selected from a protein, a fragment of the protein, a derived sequence and a homologous sequence of the protein, the protein including or being constituted by the 28 kDa glutathione S-transferase protein from a schistosome selected from Schistosoma haematobium, Schistosoma mansoni, Schistosoma bovis represented respectively by the sequences SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 3 for the use thereof in the treatment of an inflammatory autoimmune disease generating a response of type Th1 and/or Th17.


Patent
French Institute of Health, Medical Research, Lille University Hospital Center, Lille 2 University of Health and Law | Date: 2012-01-20

The present invention relates to methods and kits for predicting the risk of respiratory failure, renal failure or thrombopenia in a septic patient. More particularly, the present invention relates to a method for predicting the risk of having an organ failure selected from the group consisting of respiratory failure, renal failure and thrombopenia in a septic patient comprising a step consisting of measuring the concentration of endocan in a blood sample obtained from said septic patient.


Patent
French Institute of Health, Medical Research, University Paris Diderot and French National Institute for Agricultural Research | Date: 2013-05-21

The present invention relates to the general field of therapy of Inflammatory Bowel Disease (IBD) and/or Irritable Bowel Syndrome (IBS). Thus, the invention relates to a molecule selected from the trappin-2 protein or an active fraction thereof, a member of the WAP family proteins or an active fraction thereof or a member of the Serpin family proteins or an active fraction thereof for the treatment of Irritable Bowel Syndrome (IBS). The invention also relates to a recombinant food-grade bacterium comprising a gene selected from a gene coding for the trappin-2 protein or an active fraction thereof, a gene coding for a member of the WAP family proteins or an active fraction thereof, or a gene coding for a member of the Serpin family proteins or an active fraction thereof.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2009-2.4.4-1 | Award Amount: 8.18M | Year: 2010

Usher syndrome (USH) is the most frequent hereditary cause of deafness associated to blindness. It is a rare disease, affecting 1 in every 10.000 individuals, with an autosomal recessive monogenic inheritance. Deafness is congenital while the retinitis pigmentosa is not detected before the age of 8 to 10. These patients suffer from a dreadful disability as their two major senses are impaired. Important scientific advances have been achieved, mostly by auditory scientists: 9 causative genes have been identified. The hearing impairment pathogenesis has been elucidated, ie, an early developmental defect of auditory sensory cells. Our project gathering scientists and physicians from both the auditory and visual fields aims : -to halt the no longer acceptable underdiagnosis of this syndrome. Because, children affected with Usher type I, the most severe form, are usually diagnosed as severely or profoundly deaf only, parents may choose visual/sign language whereas these children would have taken full advantage from an early cochlear implantation. -To make these patients benefit from gene replacement therapy in the retina that recently showed tremendous results. We propose : 1/ To develop new clinical and molecular tools and guidelines for an early diagnosis thereafter broadly disseminated. 2/To clarify the retinal pathogenesis of Usher syndrome (type I and II) by an unpreceding effort to generate animal and tissue models that will be characterised in depth by multidisciplinary investigations including innovative methods. Mouse, frog, pig in vivo models and cultured retinal explants will be used, as well as human retinal cultures. This will also provide the necessary tests to evaluate phenotype rescuing. 3/To prevent and treat the retinal defect by associated adenovirus (AAV) gene therapy. This includes optimisation of the gene transfer and selection of patients to lead to a clinical trial carried out for one or more Usher genes (USH1B, 1C, 1G & USH2D)


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH-2009-2.1.2-1 | Award Amount: 14.94M | Year: 2010

AIM: To identify the molecular mechanisms characterizing cilium function, and the discrete perturbations associated with dysfunction caused by mutations in inherited ciliopathies, applying a systems biology approach. BACKGROUND: Cilia are microtubule-based, centriole-derived projections from the cell surface. They transduce extracellular signals and regulate key processes in which signals of the extracellular environment are translated into a cellular response, such as cell cycle control, Wnt signalling, Shh signalling and planar cell polarity. Disruption of cilium-based processes by mutations can cause very severe disorders. Many of these ciliopathies have overlapping phenotypes. There is evidence, that ciliary proteins are organized in cell/context specific complexes and/or in shared regulatory circuits in cilia of affected tissues. Yet, knowledge of the composition, wiring, dynamics and associated signaling pathways of the corresponding molecular building blocks and associated protein networks remains very limited. APPROACH: We propose here that ciliopathies can be considered systemically as specific perturbations in a versatile dynamically regulated multifunctional molecular machine. Mainly based on the comprehensive description of the ciliary interactome, quantitative functional assays as well as human genetic data derived from ciliopathy patients, we will generate a comprehensive stream of content-rich quantitative data towards systemic analysis of ciliar function. These data will be used to generate and validate discrete models that describe functional modules and regulatory circuits in the ciliome as well as predicting biological context specific features of cilia as well as perturbations leading to ciliopathies. This will enable us to 1) understand the systemic features of discrete ciliary functions, 2) scrutinize the molecular disease mechanisms of different overlapping ciliopathies, and 3) develop therapeutic strategies towards improved treatment.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2010.4.2-9-2 | Award Amount: 9.40M | Year: 2011

The goal of HeMiBio is to develop a hepatic microfluidic bioreactor from human iPSC-derived hepatocytes, hepatic sinusoidal endothelial cells (HSEC) and stellate cells (HSC), suitable for inclusion in a repeated dose toxicity testing strategy of pharmaceuticals/cosmetic ingredients. The successful creation of such a liver-device requires (a) homotypic and heterotypic interactions between the three cell types to induce and maintain their functional, differentiated state, and (b) optimisation of the matrix, oxygenation conditions, nutrient transport and physiological shear forces. The objectives are (1) to engineer the cellular components incorporated in the bioreactor to enable specific and spatially defined enrichment of the different cells from iPSC progeny, and, by gene editing, to allow non-invasive monitoring of the cellular state (differentiation and damage). (2) Aside from the molecular sensors, an array of electro-chemical sensors will be embedded in the reactors to assess liver-specific function and cellular health under repeated dose toxicity conditions, dynamically and in a high-throughput way. Cells and sensors will be built into (3) bioreactors that will be sequentially upgraded from 2D to 3D microfluidic reactors to ultimately allow full maintenance of mature functional hepatocytes, HSC and HSEC for >28 days. (4) As the ultimate goal is to use the device as a human-based alternative to rodent long-term hepatotoxicity studies, it will be of utmost importance to provide proof of concept that the 3D-devices reveal the hepatotoxicity of prototypical hepatotoxic compounds in vivo (5). -Omics and cell functionality studies will provide evidence that liver-like cells are present, exposed and affected by the selected toxic compounds. These ambitious objectives will be achieved by the excellent project team, composed of academic/industrial partners with unique and complementary biology, physiology, toxicology and technical skills from 7 EU Member States.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2011.2.2.2-2 | Award Amount: 3.88M | Year: 2012

The increasing number of elderly people will have a major impact on the prevalence of age-related diseases, which will pose major challenges to keep health systems in Europe sustainable. Current knowledge is insufficient to identify the transition of normal brain ageing into Alzheimer`s Disease (AD)-like brain damage. Elucidation of the genes and pathways contributing to the earliest stages of AD pathology and associated neurodegeneration should be instrumental to allow intervention when the condition is still reversible. The aim of the DEVELAGE project is to characterise shared molecular pathways between early developmental processes in the brain and brain ageing. Our concept is based on the hypothesis that disorders of neural development contribute to age-related neurodegeneration, that developmentally essential proteins might have a role in neurodegeneration, and that neurodegeneration-related proteins and genes are important during the development of the brain. The DEVELAGE approach is unique in that it is brain tissue-based, derived from neuropathological diagnosis with detailed molecular analysis of the spectrum of developmental and ageing changes in the very same brain samples used for a comprehensive array of investigations in humans as well as in experimental models at genetic, epigenetic, transcription and protein levels. DEVELAGE contributes to the understanding of biological variation by examining relevant number of cases with different phases of ageing and neurodegeneration as well as developing brains with or without developmental disorders. Pathways examined in humans will be validated in animal models, including a non-human primate, and vice versa. The combination of human samples and animal models susceptible to experimental manipulation will promote the translation of clinically relevant data into experimentally testable predictions and promotes the exploitation of therapeutically relevant targets to reverse or halt disease progresssion.


Grant
Agency: Cordis | Branch: FP7 | Program: CPCSA | Phase: ICT-2013.9.9 | Award Amount: 72.73M | Year: 2013

Understanding the human brain is one of the greatest challenges facing 21st century science. If we can rise to the challenge, we can gain profound insights into what makes us human, develop new treatments for brain diseases and build revolutionary new computing technologies. Today, for the first time, modern ICT has brought these goals within sight. The goal of the Human Brain Project, part of the FET Flagship Programme, is to translate this vision into reality, using ICT as a catalyst for a global collaborative effort to understand the human brain and its diseases and ultimately to emulate its computational capabilities. The Human Brain Project will last ten years and will consist of a ramp-up phase (from month 1 to month 36) and subsequent operational phases.\nThis Grant Agreement covers the ramp-up phase. During this phase the strategic goals of the project will be to design, develop and deploy the first versions of six ICT platforms dedicated to Neuroinformatics, Brain Simulation, High Performance Computing, Medical Informatics, Neuromorphic Computing and Neurorobotics, and create a user community of research groups from within and outside the HBP, set up a European Institute for Theoretical Neuroscience, complete a set of pilot projects providing a first demonstration of the scientific value of the platforms and the Institute, develop the scientific and technological capabilities required by future versions of the platforms, implement a policy of Responsible Innovation, and a programme of transdisciplinary education, and develop a framework for collaboration that links the partners under strong scientific leadership and professional project management, providing a coherent European approach and ensuring effective alignment of regional, national and European research and programmes. The project work plan is organized in the form of thirteen subprojects, each dedicated to a specific area of activity.\nA significant part of the budget will be used for competitive calls to complement the collective skills of the Consortium with additional expertise.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2013.2.2.1-4 | Award Amount: 16.45M | Year: 2013

DESIRE will focus on epileptogenic developmental disorders EDD, i.e. early onset epilepsies whose origin is closely related to developmental brain processes. A major cause of EDD are malformations of cortical development (MCD), either macroscopic or subtle. EDD are often manifested as epileptic encephalopathies (EE), i.e. conditions in which epileptic activity itself may contribute to severe cognitive and behavioral impairments. EDD are the most frequent drug-resistant pediatric epilepsies carrying a lifelong perspective of disability and reduced quality of life. Although EDD collectively represent a major medical and socio-economic burden, their molecular diagnosis, pathogenic mechanisms (PM) and rationale treatment are poorly understood. Specific objectives of DESIRE are to advance the state of the art with respect to: (1) the genetic and epigenetic causes and PM of EDD, particularly epileptogenic MCD, to elucidate molecular networks and disrupted protein complexes and search for common bases for these apparently heterogeneous disorders. (2) the diagnostic tools (biomarkers) and protocols through the study of a unique and well-characterized cohort of children to provide standardized diagnosis for patient stratification and research across Europe. (3) treatment of EDD using randomized, multidisciplinary clinical protocols and testing preclinical strategies in experimental models to also address novel preventative strategies. The workplan spans from clinical observation, to whole exome studies, cellular and animal models and basic research, identification of biomarkers and improvement of diagnostic methods, and back to the clinical trials and assessment of innovative, targeted treatment strategies. The consortium partners have an outstanding track record in genetics, basic neurophysiology, neuropathology and clinical research. Specialized expertise will be made available by the SMEs involved to develop novel diagnostic tools for tailored treatment approaches.


Grant
Agency: Cordis | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2011-ITN | Award Amount: 3.66M | Year: 2012

The aim of this ITN is to promote research and training in the field of epigenetics associated with human disease. Expression of imprinted genes is mono-allelic and gamete of origin-dependent. This is due to different epigenetic modifications present on the maternal and paternal chromosomes. Failure in normal establishment, maintenance or erasure of these marks results in gene dosage dysregulation and Imprinting Disorders (IDs). This ITN brings together different expertise from both public and private sectors with the aim of investigating the physiology and pathology of Genomic Imprinting. We propose to define mechanisms, molecular factors and pathways regulating DNA-methylation and chromatin dynamics involved in gene expression control in human health and disease. This concerted approach has the potential to identify new and more effective diagnostic, preventive and therapeutic strategies for IDs, and more generally to elucidate roles and origin of epigenetic mutations in human pathologies, including common diseases. Early stage (ESRs) and experienced researchers (ERs) will have access to a range of cutting-edge methodologies to enable the application of integrated multidisciplinary strategies to analyse epigenetic phenomena. The excellent scientific and educational environment and the intense public-private sector collaboration will promote high-level training of the young researchers. The ESRs and ERs will acquire experience and expertise in a variety of disciplines, including molecular, cellular and developmental biology, genomics, bioinformatics, chromatin dynamics and epigenetics and phenotypic analysis, and state-of-the-art methodologies such as gene targeting, stem cell culture, epigenetic and chromatin technologies, and massively parallel sequencing. Hence, this ITN will generate a new cohort of scientists trained in contemporary post-genomic biology and able to apply advanced technological tools to investigate human disease in both academia and industry.


Grant
Agency: Cordis | Branch: FP7 | Program: NoE | Phase: HEALTH.2010.2.3.2-3 | Award Amount: 15.96M | Year: 2011

Over the past 15 years, EU-funded cohorts and collaborations (EuroSIDA, CASCADE and PENTA), have played a central role in developing our understanding of HIV progression and the effects of ART, enabling European expertise to contribute directly to the advances in patient diagnosis and management worldwide, and providing a continued surveillance mechanism for detection of emerging problems at a European level. Furthermore, we also established COHERE (Collaboration Of HIV Epidemiologic Research in Europe), a new European-wide cohort collaboration encompassing virtually all European HIV cohorts which were not included in the EU-funded networks. COHERE provides us with sufficient statistical power to address questions that cannot be addressed by existing cohorts and networks alone. Together, these collaborations form the foundation of a proposed Network of Excellence, which we have named EuroCoord. EuroCoord currently has access to data from over 250,000 HIV-infected individuals across the European continent, and beyond, both male and female, from neonates to geriatric populations, infected through sex between men, sex between men and women, injecting drug use, nosocomially and from mother to child, with and without co-infection with hepatitis viruses, of different ethnic and socio-economic backgrounds, from indigenous and migrant populations, in settings with varying levels of access to care and laboratory techniques. Our multidisciplinary research will thus allow us to address key areas of HIV research aimed at improving the management and life of HIV-infected individuals, whilst allowing us to explore differences within sub-groups. EuroCoord is in a position to mobilise European HIV cohort research, bringing it within one truly pan-European network of cohort studies with a strong and increasing presence in the Central- and Eastern European region. The structure of our network, maintaining autonomy within each individual network but within one common research platform, ensures that the most competitive science is performed whilst allowing us to pool our expertise and resources to undertake new initiatives within an integrated collaborative structure.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2012.2.1.1-1-B | Award Amount: 15.82M | Year: 2012

EURenOmics will integrate several established consortia devoted to rare kidney diseases with eminent need and potential for diagnostic and therapeutic progress (i.e. steroid resistant nephrotic syndrome, membranous nephropathy, tubulopathies, complement disorders such a haemolytic uraemic syndrome, and congenital kidney malformations). The Consortium has access to the largest clinical cohorts assembled to date (collectively >10,000 patients) with detailed phenotypic information and comprehensive biorepositories containing DNA, blood, urine, amniotic fluid and kidney tissue. The project aims to (1) identify the genetic and epigenetic causes and modifiers of disease and their molecular pathways; (2) define a novel mechanistic disease ontology beyond phenotypical or morphological description; (3) develop innovative technologies allowing rapid diagnostic testing; (4) discover and validate biomarkers of disease activity, prognosis and treatment responses; and (5) develop in vitro and in vivo disease models and apply high-throughput compound library screening. For these purposes we will integrate comprehensive data sets from next generation exome and whole-genome sequencing, ChiP-sequencing, tissue transcriptome and antigen/epitope profiling, and miRNome, proteome/peptidome, and metabolome screening in different body fluids within and across conventional diagnostic categories. These data will be combined in a systems biology approach with high-resolution clinical phenotyping and findings obtained with a large array of established and novel in vitro, ex vivo and in vivo disease models (functiomics) to identify disease-associated genetic variants involved in monogenic or complex genetic transmission, disease-defining molecular signatures, and potential targets for therapeutic intervention. These efforts will converge in the development of innovative diagnostic tools and biomarkers and efficient screening strategies for novel therapeutic agents.


Grant
Agency: Cordis | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2011-ITN | Award Amount: 3.74M | Year: 2012

Infectious diseases caused by pathogenic micro-organisms are major causes of death, disability, and social and economic disruption for millions of people. During evolution these pathogens have developed intricate strategies to manipulate host defence mechanisms and outwit the immune system. To reduce the burden of infectious diseases it is important to increase understanding of these host-pathogen interaction mechanisms and to develop more effective strategies for drug discovery. The zebrafish holds much promise as a high-throughput drug screening model. In the last few years, zebrafish models for studying human pathogens or closely related animal pathogens have emerged at a rapid pace. The fact that zebrafish produce large amounts of embryos, which develop externally and are optically transparent, gives unprecedented possibilities for live imaging of disease processes and is the basis of novel high-thoughput drug screening approaches. In recent years good models have been developed for toxicity, safety and efficacy of drug screening in zebrafish embryos. However, the major bottleneck for development of high-throughput antimicrobial drug screens has been that infection models rely on manual injection and handling of zebrafish embryos. This limiting factor has been overcome by a unique automated injection system that will be applied in this project. The FishForPharma training network brings together leading European research groups that have pioneered the use of zebrafish infection models and partners from the Biotech and Pharma sectors that aim to commercialise zebrafish tools for biomedical applications. FishForPharma aims to deliver the proof-of-principle for drug discovery using zebrafish infectious disease models and to increase understanding of host-pathogen interaction mechanisms to identify new drug targets for infectious disease treatment. Most importantly, we aim to equip a cohort of young researchers with the knowledge and skills to achieve these goals.


Grant
Agency: Cordis | Branch: FP7 | Program: NoE | Phase: HEALTH.2010.4.2-2 | Award Amount: 12.67M | Year: 2011

Paediatric drugs (PD) lack appropriate testing. Most drugs have inadequate information about dosing regimen, dose adjustment and how to administer them. These are longstanding problems that unquestionably require concerted efforts at the international level. Both the US and the EU have introduced paediatric legislation that facilitates participation of children in research and pharmaceutical innovation but initiatives are not always coordinated and often different approaches are used to deal with the same problems. The main aim of GRiP will be to implement an infrastructure matrix to stimulate and facilitate the development and safe use of medicine in children. This implementation entails active coordination of knowledge management efforts and integrated use of existing research capacity, whilst reducing the fragmentation and duplication of activities. The consortium will primarily focus on: 1) development of a Paediatric Clinical Pharmacology Training Program; 2) Validation and harmonisation of research tools specific for paediatrics; 3) Sharing of strategies and plans; 4) Use of ongoing/planned research studies to evaluate the feasibility of proposed research tools and strategies. GRiP brings together an exceptional range of high quality leaders and stakeholders that are very active in the context of EU and US paediatric medicines research. GRiP will mobilize 21 institutions as partners and at least another 16 major networks that represent several hundreds of clinical sites and a total of more than 1000 researchers across Europe, the US and Asia. The integration of the WHO, EMA and the NIH-NICHD associated networks, including the FDA, will be a major asset not just for an effective implementation of the network activities without duplication, but also for the rapid translation of GRiP deliverables into practice. This partnership will work closely with families to provide children with safe and effective medicines.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2010.2.4.1-5 | Award Amount: 8.12M | Year: 2011

Among patients with adrenal masses Adrenocortical carcinoma (ACC) and malignant pheochromocytomas (MPH) are found with a low incidence but very unfavorable prognosis. Due to this poor clinical outcome, concomitant hormone dysregulation and limited treatment options the two cancer entities severely impact on affected patients. However, the rarity of the tumors also impedes clinical studies which are affected by fragmentation and low cohort sizes. The European Network for the Study of Adrenal Tumors (ENS@T) has recently implemented a collection of adrenal tumor related databases and defined an associated network of Biological Resource Centers devoted to research on adrenal tumors. The concurrence of recent achievements of this evolving network, the progress in the understanding of molecular mechanisms and increasing availability of specific diagnostic and therapeutic tools for adrenal cancers provides the unique opportunity to achieve unmatched progress in the implementation of both translation and clinical research dedicated to ACC and MPH. Specifically, the newly formed ENS@T-CANCER consortium will address the following topics: 1. Structuring European clinical and translational research through implementation of a virtual research environment, 2. Improving clinical outcome of patients with adrenal cancer by conducting interventional trials carried out by European centers of excellence, 3. Improvement of differential diagnosis and risk stratification of adrenal cancer, 4. Identification and validation of tools for follow-up of patients with adrenal cancer, 5. Identification of novel biomarkers for treatment response. The ultimate aim of the ENS@T-CANCER Consortium is to develop research in the field of adrenal cancers to improve diagnosis and treatment abilities. The Network will allow recruiting sufficient patients in all relevant European centers, to harmonize diagnosis criteria and to use the various technological approaches of a number of laboratories.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2010.3.1-1 | Award Amount: 3.97M | Year: 2011

Context: Very preterm infants face high risks of mortality and long-term neuro-developmental impairment. Rates of mortality and morbidity vary by a factor greater than two between European regions. This projects overriding aim is to improve these infants survival and long-term health and development by ensuring that available medical knowledge is translated into effective perinatal care. Objectives: (1) Build an empirical knowledge base concerning how scientific evidence is translated into health service provision in maternity and neonatal units by measuring the use of key medical interventions in clinical settings, identifying the factors associated with adoption of evidence-based practices and providing updated information on the effectiveness of medical practices; (2) Assess decision-making and knowledge implementation processes within units and regions to identify catalysts for evidence-based practice; and (3) Propose intervention strategies to achieve behavioural change. Study design: This project combines quantitative and qualitative approaches to assess the use of evidence-based medical interventions and determinants of use on the regional, unit and patient level in 19 European regions (550 units, 10,500 births). The project includes a population-based cohort study of very preterm infants with follow-up to 2 years of age, a survey of all maternity and neonatal units caring for these infants, semi-structured narrative interviews and focus groups in selected units and case studies on regional governance. Impact: The project will produce empirical data about the uptake of medical interventions in European maternity and neonatal units and new knowledge about catalysts for the adoption of medical knowledge. Its results will provide a methodological and conceptual basis for future scientific work on the effectiveness of intervention strategies. The project enhances cooperation and excellence in Europe by bringing together national research initiatives.


The forecasted increase in the number of older people for this century will be accompanied by an increase of those with disabilities. Disability is usually preceded by a condition named frailty that encompasses changes associated with ageing, life styles and chronic diseases. To detect and intervene on it is of outstanding importance to prevent disability, as recovery from disability is unlikely. Recent documents stress the necessity of testing the clinical utility (in terms of risk prediction, diagnosis validity and prognostic significance) of the existing definition of frailty by using combinations of clinical criteria (current definition) and lab Biomarkers (BMs). We will measure the levels of blood and urine omic-based BMs in old people selected from eight cohorts, which include up to 75,000 participants, using standardized and innovative technology (WP1). This figure will allow us to test the research questions with a high power and validity. Combining these lab BMs with clinical BMs, we will develop predictive, diagnostic and prognostic models (WP2), with its modulation by nutrition and physical activity, in general old population and in old people showing some characteristics that confer a high risk for developing frailty (selected cardiovascular risk factors and diseases) (WP4). After that, a selected set of BMs will be validated prospectively (WP3) and assessed to find the best-fitted models (WP4). These models will guide the development of the ready-to-use kits to be implemented in the clinical settings. These kits will be at the center of dissemination and exploitation activities (WP5, WP6). A well-balanced consortium distributed over the individual tasks in the respective work packages will carry it out, with a strong participation of SMEs. In summary, FRAILOMIC is original, relevant, pertinent, feasible, overcome the usual research bottlenecks on Biomarkers, and fits perfectly with the topics addressed by the HEALTH.2012.2.1.1-2 call in human subjects


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2011.2.1.1-1 | Award Amount: 39.64M | Year: 2011

In response to the call for a high impact initiative on the human epigenome, the BLUEPRINT Consortium has been formed with the aim of generating at least 100 reference epigenomes and studying them to advance and exploit knowledge of the underlying biological processes and mechanisms in health and disease. BLUEPRINT will focus on distinct types of haematopoietic cells from healthy individuals and on their malignant leukaemic counterparts. Reference epigenomes will be generated by state-of-the-art technologies from highly purified cells for a comprehensive set of epigenetic marks in accordance with quality standards set by IHEC. This resource-generating activity will be conducted at dedicated centres to be complemented by confederated hypothesis-driven research into blood-based diseases, including common leukaemias and autoimmune disease (T1D), by epigenetic targets and compound identification, and by discovery and validation of epigenetic markers for diagnostic use. By focussing on 100 samples of known genetic variation BLUEPRINT will complete an epigenome-wide association study, maximizing the biomedical relevance of the reference epigenomes. Key to the success of BLUEPRINT will be the integration with other data sources (i.e. ICGC, 1000 genomes and ENCODE), comprehensive bioinformatic analysis, and user-friendly dissemination to the wider scientific community. The involvement of innovative companies will energize epigenomic research in the private sector by creating new targets for compounds and the development of smart technologies for better diagnostic tests. BLUEPRINT will outreach through a network of associated members and form critical alliances with leading networks in genomics and epigenomics within Europe and worldwide. Through its interdisciplinarity and scientific excellence combined with its strong commitment to networking, training and communication BLUEPRINT strives to become the cornerstone of the EU contribution to IHEC.


Grant
Agency: Cordis | Branch: FP7 | Program: NoE | Phase: HEALTH.2010.2.1.2-2 | Award Amount: 16.04M | Year: 2010

The EpiGeneSys Network of Excellence aims to enable European epigenetics research to enter the arena of systems biology, a new step forward with major implications for human health. Many diseases, not explained solely by gene mutation, have rather been associated with epigenetic disorders. Following the identification of key epigenetic regulators, a move towards a systems biology approach is needed to understand their dynamic functional relationships. This NoE identified 4 areas aiming at: 1) characterizing the molecular dynamics of epigenetic systems at the single molecule and cell level, 2) linking genotypes to epigenotypes, 3) investigating how environmental, developmental and metabolic signals act upon the epigenome, and 4) understanding epigenetic inheritance through replication, mitosis and meiosis. The common objective is to address fundamental epigenetic mechanisms in quantitative terms both spatially and temporally. The ultimate goal is to express the underlying dynamic events in mathematical terms in order to model and predict how the balance between maintenance and erasure of epigenetic information varies in specific developmental contexts under normal or pathological conditions. A major effort on data management and technology will provide standardised protocols for processing, normalising, and analysing each type of epigenetics data set. Common platforms, tools and resources including a key multilayer toolbox will be implemented for wide use and easy access for researchers, within the NoE and the epigenetics community at large. This NoE will function as an essential bridge between epigenetics researchers and the systems biology community. In the NoE, 22 teams will join efforts to address Epigenetics questions from a systems biology perspective. The combination of a strong training plan together with extension through open targeted calls to recruit young talent will further contribute to build a coherent new EpiGeneSys Area of European Research.


Grant
Agency: Cordis | Branch: FP7 | Program: CSA-SA | Phase: NMP.2013.1.4-4 | Award Amount: 2.41M | Year: 2013

Stakeholder engagement and dialogue are essential to the responsible development of nanotechnologies in Europe. NANODIODE establishes an innovative, coordinated programme for outreach and dialogue throughout Europe to support the effective governance of nanotechnologies. The project integrates vital engagement activities along the innovation value chain: it combines upstream public engagement (by way of dialogues that integrate societal needs and expectations into the policy debate) with midstream engagement (by organising open innovation workshops at the level of R&D) and downstream strategies for education and communication. The overall objectives of NANODIODE are to: Develop new strategies for outreach and dialogue along nanotechnology value chains; Organise engagement and dialogue at the upstream level of research policy; Enable processes of co-creation during research and innovation; Professionalise nanotechnology education and training; Establish an innovative programme for outreach and communication on nanotechnologies; Assess the impact of the projects activities and provide policy feedback with a view to Horizon 2020. The consortium brings together a strong network of partners from various backgrounds and extending across Europe (representing academia, industry, civil society, education and communication). Many partners bring their experience as coordinators of earlier European projects (such as NANOCODE, NANOREG, NANOEIS, NANOCAP, NANOPLAT, OBSERVATORY NANO, NANOPINION, NANOCHANNELS and NANOBIORAISE). This will allow the project to look back and identify best practices based on existing experience - and developing new, innovative models and tools for outreach and dialogue when necessary. The project will also look ahead: as Horizon 2020 unfolds, the project will provide best practices for the effective governance of nanotechnologies in Europe.


Grant
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: Health | Award Amount: 1.76M | Year: 2014

The Ebola virus disease (EVD) epidemic in West Africa is not under control. This proposal has immediate, mid-term and long-term objectives to combat the current and future EVD epidemics. Objectives with immediate impact are: (i) Providing key information needed to implement efficient convalescent plasma treatment and a toolkit to determine the suitability of plasma for treatment; (ii) Providing key information needed to estimate the efficacy of experimental vaccines, including correlates of protection at T cell level; (iii) Improving supportive treatment of patients and reducing hospital case fatality rate by providing information on biomarkers and relevant co-infections; (iv) Monitoring development of mutations in Ebola virus (EBOV) genomes during the epidemic and enhancing our preparedness to determine the relevance of these changes in experimental systems; and (v) Protecting health care workers and communities by providing information on virus shedding in body fluids and estimation of infectiousness in various stages of EVD. Objectives with mid to long-term impact are: (i) Provide information on pathophysiological changes and immunological determinants to infer new immunotherapeutic strategies for treatment of EVD; and (ii) Strengthening cooperation of biosafety level 4 (BSL-4) facilities and building a pan-European research area in the field of highly pathogenic viruses as envisaged in the European Research Infrastructure on Highly Pathogenic Agents project. The concept of EVIDENT is to scientifically exploit specimens collected from EVD patients during outbreak response and field research. We will use state-of-the-art methodologies within the EU BSL-4 facilities to gather new and outbreak-relevant knowledge on B and T cell immunology, biomarkers, virus evolution, virulence determinants, and transmission of EBOV. The consortium contributes to the outbreak response since March 2014 and is competent to implement a project in the outbreak area.


Grant
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: Health | Award Amount: 2.85M | Year: 2014

The ongoing Ebola outbreak in West Africa is the largest and deadliest the world has ever seen. In September 2014, the number of EBOV cases exceeded the total of all cases from previous known outbreaks. Further, this public health crisis shifted into a complex emergency, with significant, social, economic, humanitarian, political and security dimensions. Till date, no effective medicine has been proven to be effective against EBOV. As a result, it is immensely difficult to mitigate the current outbreak as well as prevent further outbreaks in this region. On Sept 4-5 2014, the WHO gathered expertise on experimental therapies and vaccines and their role in containing the Ebola outbreak in West Africa. During this consultation, experts identified several therapeutic and vaccine interventions that should be the focus of priority evaluation. Among these candidates is the existing antiviral drug Favipiravir, that has proven activity against many RNA viruses in vivo and in vitro including Ebola. Favipiravir is known to inhibit viral gene replication within infected cells to prevent propagation among which it inhibits viral gene replication within infected cells to prevent propagation. Hence, Favipiravir is currently aimed as a curative option in severe pandemic flue. Furthermore, there is currently enough stock of Favipiravir to even treat more than 20.000 patients, and the producer of Favipiravir, Toyoma Chemical/Fujifilm in Japan is willing to rapidly upscale the production of this drug. This drug has been extensively tested in humans and approved in Japan for treatment and prevention of influenza. The drug has shown an excellent safety profile in more than 2000 patients tested and no major adverse effect were reported. The current crisis requires both an immediate response to treat patients and prevent the further spread of the epidemic, as well as long term commitment in the complex sociocultural context. REACTION! will address both needs.


Grant
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: SC1-PM-04-2016 | Award Amount: 7.35M | Year: 2017

Over 130,000 children born in Europe every year will have a congenital anomaly (CA; birth defect). These CAs, which are often rare diseases, are a major cause of infant mortality, childhood morbidity and long-term disability. EUROCAT is an established European network of population-based registries for the epidemiologic surveillance of CAs. EUROlinkCAT will use the EUROCAT infrastructure to support 21 EUROCAT registries in 13 European countries to link their CA data to mortality, hospital discharge, prescription and educational databases. Each registry will send standard aggregate tables and analysis results to a Central Results Repository (CRR) thus respecting data security issues surrounding sensitive data. The CRR will contain standardised summary data and analyses on an estimated 200,000 children with a CA born from 1995 to 2014 up to age 10, enabling hypotheses on their health and education to be investigated at an EU level. This enhanced information will allow optimisation of personalised care and treatment decisions for children with rare CAs. Registries will be supported in using social media platforms to connect with families who live with CAs in their regions. A novel sustainable e-forum, ConnectEpeople, will link these families with local, national and international registries and information resources. ConnectEpeople will involve these families in setting research priorities and ensuring a meaningful dissemination of results. Findings will provide evidence to inform national treatment guidelines, such as concerning screening programs, to optimise diagnosis, prevention and treatment for these children and reduce health inequalities in Europe. An economic evaluation of the hospitalisation costs associated with CA will be provided. The CRR and associated documentation, including linkage and standardisation procedures and ConnectEpeople forum will be available post-EUROlinkCAT thus facilitating future local and EU level analyses.


Grant
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: SC1-PM-22-2016 | Award Amount: 15.59M | Year: 2016

ZIKAlliance is a multidisciplinary project with a global One Health approach, built: on a multi-centric network of clinical cohorts in the Caribbean, Central & South America; research sites in countries where the virus has been or is currently circulating (Africa, Asia, Polynesia) or at risk for emergence (Reunion Island); a strong network of European and Brazilian clinical & basic research institutions; and multiple interfaces with other scientific and public health programmes. ZIKAlliance will addrees three key objectives relating to (i) impact of Zika virus (ZIKV) infection during pregnancy and short & medium term effects on newborns, (ii) associated natural history of ZIKV infection in humans and their environment in the context of other circulating arboviruses and (iii) building the overall capacity for preparedness research for future epidemic threats in Latin America & the Caribbean. The project will take advantage of large standardised clinical cohorts of pregnant women and febrile patients in regions of Latin America and the Caribbean were the virus is circulating, expanding a preexisting network established by the IDAMS EU project. I will also benefit of a very strong expertise in basic and environmental sciences, with access to both field work and sophisticated technological infrastructures to characterise virus replication and physiopathology mechanisms. To meet its 3 key objectives, the scientific project has been organised in 9 work packages, with WP2/3 dedicated to clinical research (cohorts, clinical biology, epidemiology & modeling), WP3/4 to basic research (virology & antivirals, pathophysiology & animal models), WP5/6 to environmental research (animal reservoirs, vectors & vector control) , WP7/8 to social sciences & communication, and WP9 to management. The broad consortium set-up allow gathering the necessary expertise for an actual interdisciplinary approach, and operating in a range of countries with contrasting ZIKV epidemiological status.


Grant
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: SC1-PM-04-2016 | Award Amount: 9.71M | Year: 2017

The projects overall aim is to improve the health, development and quality of life of children and adults born very preterm (VPT, < 32 weeks of gestation) or very low birth weight (VLBW, < 1500g) approximately 50 000 births each year in Europe by establishing an ICT platform to integrate, harmonise and exploit the wealth of data from 20 European cohorts of VPT/VLBW children and adults and their families constituted from the early 1980s to the present, together with data from national registries. VPT/VLBW births have higher risks of cerebral palsy, visual and auditory deficits, impaired cognitive ability, psychiatric disorders and social problems than infants born at term and account for more than a third of the health and educational budgets for children. They may also face higher risks of non-communicable disease as they age. There is emerging evidence of reduced mental health, quality of life, partnering, family life and employment chances and wealth in adulthood. The platform will enable stratified sub-group analyses of sociodemographic and clinical characteristics, neonatal complications, and otherwise rare medical conditions that cannot be studied in national population cohorts. The broad temporal, geographic, cultural and health system diversity makes it possible to study the impact of socioeconomic and organisational contexts and determine the generalisability of outcomes for VPT/VLBW populations. The RECAP platform creates a value chain to promote research and innovation using population cohorts, beginning with the integration of VPT/VLBW cohorts to the translation and dissemination of new knowledge. It will be based on a sustainable governance framework, state-of-the art data management and sharing technologies, tools to strengthen research capacity, a hypothesis-driven research agenda and broad stakeholder participation, including researchers, clinicians, educators, policy makers and very preterm children and adults and their families.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2010.2.3.2-2 | Award Amount: 8.47M | Year: 2011

Early stage Drug Discovery efforts over the last 5 years have resulted in the identification of a number of promising lead compounds in the fight against TB. These leads need to be further progressed and optimised into candidates for pre-clinical development through the Drug Development progression cascade. Three compound families are of particular interest: 1) InhA Inhibitors, 2) New potent whole cell anti-tubercular compounds with unknown mode of action and 3) new Beta-lactam/Beta-lactamase combinations for TB. A preclinical package is already in place for some of them, but further work is necessary for others in order to justify the progression of a single anti-tubercular family to the more resource intensive stages of preclinical and clinical development. The project will encompass the parallel progression of the three compound families through: A) Lead Optimization Chemistry efforts and MoA studies (Genetic and Proteomic) for whole cell inhibitors, B) In vitro and in vivo evaluation of a new orally bioavailable Beta-lactam alone or in combination with a Beta-lactamase inhibitor to evaluate the sterilising potential of the new drug/s and C) the optimization of an InhA inhibitor for later preclinical development. These efforts will yield candidate molecules for new information rich in vitro assays of antimycobacterial activity (artificial granuloma, activity against slow/non growing cells and activity against clinical isolates) as well as for in vivo safety and efficacy evaluation in different animal models of infection (acute and/or chronic). At this stage a single compound family will be prioritized. Further studies will be performed assessing the potential for shortening treatment in stand alone therapy as well as in combination regimens both in vitro and in vivo. Finally a Clinical Development plan will be put in place for the selected candidate molecule.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP-SICA | Phase: HEALTH.2010.2.3.4-2 | Award Amount: 6.45M | Year: 2010

Neglected Infectious Diseases (NID) such as trypanosomiasis, leishmaniasis, schistosomiasis and soil-transmitted helminthiasis receive less than 5% of the global investment for tropical diseases research. Clinical praxis in disease-endemic countries (DEC) is rarely evidence based and does not make use of the latest innovations in diagnostic technology. NIDrelated research on diagnostics is particularly underfunded, and diagnostic tools are lacking for a number of NID. The aim of this proposal is to bridge the gap between existing technological innovation in diagnostics and clinical care practice for NID in resource-poor settings. The specific objectives are to develop simple, cost-effective diagnosis-treatment algorithms for three NID-related clinical syndromes: the persistent fever, the neurological and the digestive syndromes. Evidence-based algorithms for the primary care level will be designed with a patient-centred approach, following guidance from DEC stakeholders and making the best possible use of existing assays and treatments. Relevant diagnostic technology and diagnostic platforms will be introduced according to the specific epidemiological contexts in Africa and South-Asia. The research consortium brings together a network of clinical epidemiologists, a diagnostics development group, several partners from academia and SMEs. The consortium further includes workpackages on reference laboratory, economic evaluation, quality assurance and translation to policy. By developing accurate and affordable diagnostic platforms and by optimizing diagnostic-treatment algorithms, this project will rationalise treatment use, circumvent progression to severe presentations and thereby reduce NID morbidity/mortality and hinder the emergence of resistances. The project will result in two main deliverables: policy recommendation for health authorities in DEC, and a series of innovative diagnostic platforms.


Grant
Agency: Cordis | Branch: H2020 | Program: ERC-ADG | Phase: ERC-ADG-2014 | Award Amount: 3.50M | Year: 2016

To understand how the brain works, tools need to be developed that will allow neuroscientists to investigate how interactions between individual neurons lead to emergent networks. Towards this goal, we will develop targetable voltage sensing nanorods that self-insert into the cell membrane and optically and non-invasively record action potentials at the single particle and nanoscale level, at multiple sites and across a large field-of-view. In semiconductors, absorption and emission band edges are modulated by an external electric field, even more so when optically excited electron-hole pairs are confined, giving rise to the quantum confined Stark effect. The physical origin of this effect is in the separation of photoexcited charges, creating a dipole that opposes the external field. The proposed sensors will optically record action potential with unique advantages not offered by other methods: much larger voltage sensitivity, high brightness, and hence single-particle voltage sensitivity, large spectral shift (affording noise-immune ratiometric measurements), fast temporal response, minimal photobleaching, large Stokes shifts, large two-photon excitation cross sections, excellent performance in the NIR, and compatibility with lifetime imaging. The proposed sensors could afford, for example, the recording of pre- and post-synaptic membrane potentials, sub-threshold events, ultrafast spiking, individual ion channel activity, or a release of ions from single Ca\2 stores. In addition, deep tissue imaging could be afforded by two photon microscopy and far-field non-linear temporal focusing combined with lifetime imaging. Here we seek to optimize all aspects of the sensors synthesis, functionalization, delivery, targeting and detection, in order to provide neuroscientists and physiologists a viable and user-friendly technology that will be generally useful for the study of action potential signals in the brain and in healthy or diseased heart and muscle tissues.


Grant
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: NMBP-09-2016 | Award Amount: 6.23M | Year: 2017

Optogenerapy proposes a new interferon- (IFN-) drug delivery system to revolutionize Multiple Sclerosis treatment. The aim is to develop and validate a new bio-electronic cell based implant device to be implanted subcutaneously providing controlled drug release during at least 6 months. The cell confinement within a chamber sealed by a porous membrane allows the device to be easily implanted or removed. At the same time, this membrane acts to prevent immune rejection and offers long-term safety in drug release while overcoming the adverse effects of current cellular therapies. Wireless powered optogenetics light controlling the cellular response of genetically engineered cells is used to control the production of IFN-. Replacing standard intravenous IFN- delivery by subcutaneous delivery prevents short and long term side effects and efficiency-losses related to drug peaks and discontinuation, while saving non-adherence costs. It is a low-cost system enabling large scale manufacturing and reduction of time to market up to 30% compared to other cell therapies, combining: - Polymeric biomaterials with strong optical, biocompatibility and barrier requirements, to build the cell chamber and to encapsulate the optoelectronics. - Optoelectronics miniaturization, autonomy and optical performance. - Optimal cellular engineering design, enhanced by computer modelling, for stability and performance of the synthetic optogenetic gene pathway over long-term implantation. - Micro moulding enabling optoelectronics and membrane embedding for safety and minimal invasiveness. The innovation potential is so huge that a proof-of-concept was listed by Scientist Magazine as one of the 2014s big advances in science. In our top-class consortium, industrial pull meets technological push, ensuring that the preclinically validated prototype obtained at the end responds to market demands. BOSTON SCIENTIFIC, worldwide leader in neuromodulation active implants, has clear exploitation plans and high market penetration potential. 4 research intensive SMEs: TWO, GENEXPLAIN, NEOS and ULTRASION bring specific competences while increasing their own competitiveness.


Recent epidemiological studies suggest that cancer risk after exposures with doses comparable to the dose limits for occupationally exposed workers may be larger than assumed by ICRP in the derivation of these limits. The value of cancer risk from such exposures and its dependence on tissue, radiation type and individual factors is largely unknown. The innovative approach proposed here combines epidemiology and radiobiology in order to quantify cancer risks after low-dose or low-dose-rate exposures to ionizing radiation. Key factors of radiation induced carcinogenesis such as genomic instability will be measured in cancer tissues and blood samples from members of the following radio-epidemiological cohorts: French Haemangioma Cohort, Mayak Worker Cohort and thyroid cancer cases after the Chernobyl accident. Inter-cellular communication after exposure to low-dose radiation exposure and its influence on apoptosis, cell proliferation, differentiation and genomic instability will be explored with 2D cell cultures and 3D tissue models. This includes research on stem cells, which will be isolated from healthy human breast tissue. The results of the radiobiological studies will be integrated in the development of models of carcinogenesis for evaluation of major epidemiological cohorts: Atomic Bomb Survivors, French-Swedish-Italian Thyroid Cancer Cohort, Mayak Worker Cohort, Swedish Haemangioma Cohort, UkrAm Cohort on thyroid cancer after the Chernobyl accident, and UK National Registry for Radiation Workers. Cancer risk will be determined for the breast, lung, thyroid and the digestive tract after low-dose-rate exposure to low-LET radiation (external gamma radiation and internal radiation from 131I) and to high-LET radiation (alpha-particles from incorporated plutonium). Lifetime cancer risks including individual risk factors will be calculated to establish a new basis for deriving dose limits and estimating cancer risks including those from medical diagnostic exposures.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.2.4.1-2 | Award Amount: 8.20M | Year: 2013

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and accounts for about 6% of all new cancer cases worldwide. Given the lack of available effective treatments, the overall prognosis for HCC patients is poor, with a dismal 5-year survival of 5-6%. The main goal of this proposal is to develop a therapeutic cancer vaccine aiming at improving clinical outcome in early-stage HCC patients after loco-regional ablative therapy. HepaVac is an European consortium of academic, SME and pharmaceutical company partners with complementary and substantial expertise in cancer immunotherapy and vaccine development. The main objective of HepaVac is to develop a novel cancer vaccine approach for HCC based on epitopes naturally processed and presented by HLA class I and II (HLA-ligandome), to elicit both CD4\ T helper and CD8\ CTL tumor-specific effector and memory responses. The HCC HLA-ligandome will be identified in primary tumor tissues using a combined and integrated approach, developed and thoroughly validated by Partners #2 and #5. The selected peptide epitopes will constitute the candidate cancer vaccine for HCC, aiming at covering the broadest haplotype diversity with a multi-epitope and multi-TAA strategy. T cell epitopes derived from universal TAA and unique patient-specific mutated antigens will allow the design of a prime-boost vaccine strategy based either on a prime-boost schedule made of an off-the-shelf T cell epitope cocktail or on a schedule where the boost is complemented by a personalized T cell epitope cocktail. Both epitope cocktails will be adjuvanted in a novel and potent immunomodulator developed by Partner #6. Such a vaccination strategy will be tested in a randomized controlled multi-center phase I/II human clinical trial, assessing as primary endpoints safety and induction of specific cellular immune responses and, as secondary endpoints, OS and PFS of patients receiving the vaccine after tumor ablation vs tumor ablation alone.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2010.2.4.2-1 | Award Amount: 7.98M | Year: 2010

According to the European Society of Cardiology there has been an increase in the life expectancy at the age of 65 of the European population from 15.0 to 17.0 years in the years since 1980. In the elderly, up to 50% of deaths are caused by cardiovascular diseases, the majority accounted for by coronary artery disease. The most effective treatment for obstructive coronary disease is percutaneous intervention with coronary stenting and fuelled by the increasing disease burden there has been a rapid increase in the number of percutaneous coronary intervention procedures in Europe from 184,000 in 1992 to 885,000 in 2004. If the rate of progression remains constant, the projected number of coronary intervention procedures per annum will be about 1.5 million by 2010, with a stenting rate of close to 100%. The principal safety issue with current coronary stenting procedures is late stent thrombosis which, with a case mortality rate approaching 50%, makes this problem a very significant European health issue. The PRESTIGE project will result in significant improvement in prediction and prevention of late stent thrombosis by providing novel strategies that causally impede incident events without increasing the overall risk of bleeding. These goals will be achieved by a multidisciplinary consortium formed by world-leading EU-based specialists covering the requisite scientific skills and experience. Since the first drug-eluting stent was introduced in 2002 the growth of this sector has been explosive. Forecasts predicted the potential for this market segment to exceed 4.6 billion by 2009. The economic impact of this very ambitious project will be to provide the European health industries with novel stent products and new imaging technologies to identify patients at-risk, as well as amended European treatment guidelines. The social impact will be, amongst others, a tremendous cost reduction for the public and private health insurance systems all over Europe.


Grant
Agency: Cordis | Branch: FP7 | Program: CSA-CA | Phase: HEALTH.2011.4.1-1 | Award Amount: 2.25M | Year: 2011

The overall aim of CommHERE is to improve communication on the outcome of EU funded health research projects to the media, the general public and other target groups including the EC in all of Europe. The CommHERE consortium comprises 10 partners, all research institutions active in the health research area. All partners are responsible for the coordination of EU-funded health research projects. This strong EU research connection is crucial for the proposed project plan, since it gives the consortium the possibility to work in close contact with the actual performers of health research. The general concept of CommHERE is to act on parallel levels which both are developed during the project period. On the one hand there will be an increase in actual communication activities on ongoing research directed towards the media, various stakeholders and the general public by production of press releases, virtual texts and images, and outreach activities. Basic tools and guidelines for this, applicable on a European level, will be prepared, used and developed. On the other hand for a long-term sustainable effect the project participants will work closely with the PIs and other representatives of new and ongoing research projects to encourage and motivate them, by giving tools, feed-back and incentives for continuous communication also outside of the scientific community. All activities will initially be made on a local level, within each of the participants institutions, but towards a European audience. The guidelines, experiences and any good examples will successively be spread nationally and between countries. A network of communication officers from all parts of Europe will stimulate future collaboration, sharing of experiences and competence building.


Grant
Agency: Cordis | Branch: FP7 | Program: ERC-AG | Phase: ERC-AG-SH3 | Award Amount: 2.31M | Year: 2014

This project aims at a socio-historical study of the transition between the two regimes of knowledge and action, which have characterized the government of health after World War II: the regime of international public health, dominating during the first decades of the postwar era, which was centered on eradication policies, nation-states and international UN organizations; the present regime of global health, which emerged in the 1980s and is centered on risk management and chronic diseases, market-driven regulations, and private-public alliances. The project seeks to understand this transition in terms of globalization processes, looking at the making of knowledge, the production and commercialization of health goods, the implementation of public health programs, and routine medical work. It will focus on four fields of investigations: tuberculosis, mental health, traditional medicine and medical genetics in order to understand how categories, standardized treatment regimens, industrial products, management tools or specific specialties have become elements in the global government of health. The project associates historical and anthropological investigations of practices in both international and local sites with strong interests in: a) the changing roles of WHO; b) the developments taking place in non-Western countries, India in the first place. The expected benefits of this research strategy are: a) to take into account social worlds including laboratories, hospitals, enterprises, public health institutions and international organizations; b) to approach the global as something translated in and emerging from local practices and local knowledge; c) to explore different levels of circulations beyond the classical question of North-South transfers; d) to deepen our understanding of the transition from the political and economical order of the Cold War into a neo-liberal and multi-centric age of uncertainty.


Grant
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: PHC-32-2014 | Award Amount: 3.00M | Year: 2015

Cancer treatment platforms that involve the use of the adaptive immune system have demonstrated profound tumour regressions including complete cure. Importantly, technological advances in next-generation sequencing (NGS) allow for the first time the development of personalised cancer immunotherapies that target patient specific mutations. However, clinical application is currently hampered by specific bottlenecks in bioinformatics, which we aim to address in this proposal. The overall objective of our trans-disciplinary network of leading experts in bioinformatics and cancer immunology is to develop an Advanced bioinformatics platform for PERrsonalised cancer IMmunotherapy (APERIM). Specifically we aim to develop: 1) database for the integration of NGS data, images of whole tissue slides of tumour sections, and clinical data. To enhance the usability and the data sharing we will use semantic web technologies, and will provide standardised interfaces to a set of analytical tools. 2) tools for automated quantification of tumour-infiltrating lymphocytes using whole tissue slide images and NGS data for patient stratification. 3) analytical pipeline for NGS-guided individualised cancer vaccines including crucial NGS data analysis and epitope selection components for the selection of vaccination targets. 4) a method for deriving T-cell receptor (TCR) sequences from NGS data and predicting TCR specificity. We will achieve these aims using unique training and validation datasets available to the consortium. We will develop user-friendly software modules as well as analytical standard operating procedures for clinical use, and apply the bioinformatics platform in clinical settings. The bioinformatics platform will considerably accelerate the clinical translation and maximise the accessibility and utility of biomedical data in research and medicine.


Grant
Agency: Cordis | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2012-ITN | Award Amount: 3.09M | Year: 2012

Eye research has often blazed a trail for other disciplines to follow, giving a lead in neuroscience, genetics, the development of gene- and stem-cell therapies and other important areas of medical research. In recent years, geneticists have made many remarkable discoveries of relevance both to normal human vision and the development of inherited retinal pathology. However the genes and mutations identified account for only a proportion of cases of inherited retinal degeneration, and recent discoveries hint at new classes of mutations which are either largely undetected or the significance of which is missed by conventional genetics. In addition, for those genes implicated there often remains a black box between mutations and disease; how do defects in a given protein manifest symptoms in the eye and what underlies the huge variation in symptoms, severity and response to treatment? The objectives of EyeTN are twofold; to address these knowledge gaps through cutting edge research using novel techniques, including transcriptomics analyses, whole genome and single target RNAi, the development of animal and cell-based disease models, stem cell biology, bioinformatics and hands on experience of pharmaceutical research with direct translational targets; and to give the next generation of European ophthalmic researchers unparalleled opportunities to train with a consortium of the best inherited blindness research labs in the world. The Network spans academic, healthcare and commercial research sectors and is already well established with many existing collaborations. All fellows will carry out one or more components of their research and training in a commercial environment and attend a workshop on translating ideas and discoveries into commercially viable Bioscience produces and therapies, fostering an entrepreneurial mindset and ensuring that we train a pool of researchers who are able to communicate effectively with both academic and commercial bioscience colleagues.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2010.2.4.5-2 | Award Amount: 7.31M | Year: 2010

The ALLFUN proposal aims at defining the cellular and molecular mechanisms by which ubiquitous airborne or commensal fungi contribute to immune homeostasis and its dysregulation leading to allergy and inflammatory diseases. Breakthroughs in understanding how mucosal homeostasis is established, maintained or disrupted in the presence of fungi should be sources of new therapeutic targets and drugs (i.e. anti-inflammatory, immunomodulatory and anti-infectious molecules). European scientists representing the leading edge of this field are brought together here in a unique synergistic and cross-cutting collaboration that addresses a major medical and economic problem of considerable importance to the health care sector. The study will be centered on yeasts and filamentous fungi known to be associated with a number of inflammatory, autoimmune and allergic diseases. Via a multidisciplinary systems biology study combining fungal genetics, clinical research and animal models in a systems biology approach, integrating traditional wet-lab methods with those of functional genomics, immunomics, allergomics and bioinformatics, the ALLFUN project meets the criteria of the call, the strategic objective of which is to elucidate mechanisms by which infections may lead to aberrant activation of inflammation, the lack of resolution of which is responsible for inflammatory diseases. The anticipated results are highly relevant to society in terms of reducing the burden of mortality and suffering in patients with fungus-related diseases, identifying more accurate biomarkers for immunological disorders, optimizing and possibly reducing the cost of antifungal therapy by association with anti-inflammatory strategies that targets pathogenicity rather than microbial growth, the host-pathogen interface rather than the pathogen. Understanding the spectrum of immunological responses to fungi is perhaps the single most important challenge in the field of medical mycology.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-CSA-Infra | Phase: INFRA-2011-2.3.2. | Award Amount: 13.73M | Year: 2012

The ESFRI infrastructures in Biological and BioMedical Sciences face substantial challenges in accessing and sharing data and resources. The BioMedBridges consortium brings together the six established ESFRI infrastructures with common goals to define, implement and deliver data interoperability across the biological and biomedical domains. The first objective is to ensure that interoperable standards are available across all data resources and services shared by two of more ESFRI infrastructure. The identified standards will be implemented to enable data interoperation between ESFRI projects in biomedical sciences. Public data in life sciences will be freely accessible through these standard interoperable services. Private data, however, is a major concern in this domain, for medical information or for data with intellectual property issues. Where projects need to share sensitive data, standards for secure and restricted access will be identified and implemented. BioMedBridges is a practical solution to the data interoperability requirements of infrastructures in the biological and biomedical domains. A suite of use cases will guide the development and deployment of standards and services with emphasis on the issues arising between specific projects. These may cover the exchange of biomedical and genetic data, linking mouse model organism data with human clinical information, and the deposition of large volumes of data from one project to another. BioMedBridges is inclusive of emerging infrastructures which can contribute additional data classes and challenges such as bioimaging, ecosystems, small molecules and infectious diseases. The ESFRI infrastructures leading BioMedBridges are ELIXIR, BBMRI, EATRIS, ECRIN, InfraFrontier and INSTRUCT.


Grant
Agency: Cordis | Branch: FP7 | Program: CSA-CA | Phase: HEALTH.2010.1.2-3 | Award Amount: 2.25M | Year: 2011

EuroGentest is an FP6 European network for the harmonization of genetic testing and for the further improvement of quality in genetic services across Europe. This proposal is to support EuroGentest2, a Coordination Action that will cover the different aspects of quality assurance of genetic practice and has all the ingredients to fulfil the needs. EuroGentest2 will be concerned with setting the targets for laboratory and health professional accreditation, by contributing to guidelines and standards, and actively interacting with the professional organizations and the policy makers. EuroGentest2 will also assist the diagnostic and clinical community and the individual laboratories and counselling units in reaching those aims by providing tools for quality management and by coordinating training activities. EuroGentest2 will extend its activities from postnatal diagnostic and predictive testing to prenatal testing, thereby building on the achievements of the FP6 SAFE network, and to direct to consumer testing. A major aim of the Coordination Action will be the creation of a European association of genetic diagnostic centres that will guarantee the future of the network. The Coordination Action will lead to the further harmonization and quality assurance of genetic practice. The patients will benefit by the improvement of the analytical and clinical quality and validity of the testing, and from improved trans-border services and information. The European diagnostics industry will benefit through a faster access of innovations to the market through the validation for diagnostic use. It will enable countries and regions with less developed health care infrastructure to develop standards for best practice of provision of clinical genetic service. The Coordination Action will also identify research needs and have the capacity to set a research agenda that corresponds to the needs of the human genetics community


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.4.2-3 | Award Amount: 2.92M | Year: 2014

The HEALTH.2013.4.2-3 call identifies a need for new or improved statistical methodology for clinical trials for the efficient assessment of safety and/or efficacy of treatment for small population groups. This project brings together international experts in innovative clinical trial design methodology in these specific areas along with key stakeholders including regulatory authorities, industry, clinicians and patient groups to address this need. Our aim is the development novel methodology for the design and analysis of clinical trials in small populations. We will focus on four specific areas where we believe there are particular challenges: (i) early phase dose-finding studies in small populations, (ii) decision-theoretic methods for clinical trials in small populations, (iii) confirmatory trials in small populations and personalised medicines, (iv) use of evidence synthesis in the planning and interpretation of clinical trials in small populations and rare diseases. We will build on recent research advances, of our own and of others in this area. In the rare disease setting, we will focus on Bayesian and decision-theoretic methods that formally enable comparison of the gain in information with the cost, both in economic and opportunity terms, of clinical experimentation, and assess how information from outside the trial can formally be incorporated in the design and decision-making processes. In the personalised medicine setting, we will develop methods that allow evaluation of efficacy in a number of sub-populations simultaneously in a confirmatory clinical trial without any reduction in scientific or statistical rigour.


Grant
Agency: Cordis | Branch: FP7 | Program: CSA-CA | Phase: HEALTH.2012.2.1.2-3 | Award Amount: 3.67M | Year: 2012

The aim of CASyM is a combined large scale effort to sustainably implement Systems Medicine across Europe. For that purpose CASyM will function as a managing and coordinating platform in bringing together a critical mass of relevant European stakeholders such as Systems Biology scientists, clinicians, programme managers, industry/SMEs as well as healthcare providers and patient organizations. The goal of that initial nucleus of experts is the development of a strategy to implement the Systems Biology approach into medical practice and research within the 4 years duration of CASyM. For this purpose it is essential that the involved communities build a vision and coordinated strategy. Our joint effort gathers extensive experience in the coordination and realization of such a new, large-scale European effort, thereby providing the basis for an advanced future medicine. The output of CASyM will be a conceptual framework defining the remits, milestones, mechanisms and metrics for the implementation of Systems Medicine. The development of this framework will overcome competitive barriers and proceed to produce a European roadmap for Systems Medicine as concerted project result.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-CSA-Infra-PP | Phase: INFRA-2010-2.2.7 | Award Amount: 6.99M | Year: 2010

Euro-BioImaging brings together imaging technologies stretching from basic biological imaging with advanced light microscopy, in vivo molecular imaging of single cells to animal models up to the clinical and epidemiological level of medical imaging of humans and populations. Euro-BioImaging, in close consultation with its stakeholders, will address the imaging requirements of both biological and medical imaging research communities by creating a coordinated and harmonized plan for infrastructure deployment in Europe. Euro-BioImaging infrastructures will be planned to provide access to state-of-the-art equipment as well as to provide training and continue the development of imaging technologies to be able to offer them as new services. The vision of Euro-BioImaging is to provide a clear path of access to imaging technologies for every biomedical scientist in Europe. The Euro-BioImaging infrastructure will be focused on imaging technologies grouped around different scales of biological organization, from the single molecule to the whole human organism. Euro-BioImaging will therefore develop a plan to construct and operate a set of complementary and strongly interlinked infrastructure facilities appropriately distributed across the European member states. To achieve this, Euro-BioImaging will define the legal and governance framework with its currently 22 member states and develop a finance plan in close cooperation with national funding bodies as well as with the European Commission. The key objective of the Euro-BioImaging preparatory phase project is to integrate these plans into an overarching business plan that provides a realistic basis for construction and operation of the Euro-BioImaging infrastructure. Through the combination of these technological and strategic objectives, Euro-BioImaging will be able to address the key elements of successful infrastructures: supporting research, training and innovation in biomedical imaging across Europe.


Grant
Agency: Cordis | Branch: FP7 | Program: CP | Phase: ENV.2012.6.4-3 | Award Amount: 11.29M | Year: 2013

The aim of HELIX is to exploit novel tools and methods (remote sensing/GIS-based spatial methods, omics-based approaches, biomarkers of exposure, exposure devices and models, statistical tools for combined exposures, novel study designs, and burden of disease methodologies), to characterise early-life exposure to a wide range of environmental hazards, and integrate and link these with data on major child health outcomes (growth and obesity, neurodevelopment, immune system), thus developing an Early-Life Exposome approach. HELIX uses six existing, prospective birth cohort studies as the only realistic and feasible way to obtain the comprehensive, longitudinal, human data needed to build this early-life exposome. These cohorts have already collected large amounts of data as part of national and EU-funded projects. Results will be integrated with data from European cohorts (>300,000 subjects) and registers, to estimate health impacts at the large European scale. HELIX will make a major contribution to the integrated exposure concept by developing an exposome toolkit and database that will: 1) measure a wide range of major chemical and physical environmental hazards in food, consumer products, water, air, noise, and the built environment, in pre and postnatal periods; 2) integrate data on individual, temporal, and toxicokinetic variability, and on multiple exposures, which will greatly reduce uncertainty in exposure estimates; 3) determine molecular profiles and biological pathways associated with multiple exposures using omics tools; 4) provide exposure-response estimates and thresholds for multiple exposures and child health; and 5) estimate the burden of childhood disease in Europe due to multiple environmental exposures. This integration of the chemical, physical and molecular environment during critical early-life periods will lead to major improvements in health risk and impact assessments and thus to improved prevention strategies for vulnerable populations.


Grant
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: PHC-01-2014 | Award Amount: 7.27M | Year: 2015

This programme of work will advance the understanding of the combined effects of factors that cause poor lung function, respiratory disability and the development of COPD . This will be achieved by examination of determinants of lung growth and lung function decline within existing cohorts that cover the whole life course, and which have followed, in detail, the respiratory health status of over 25000 European children and adults from the early 1990s to the present day. Following a comprehensive programme of risk factor identification we will generate a predictive risk score. The programme includes 1) identification of behavioural, environmental, occupational, nutritional, other modifiable lifestyle, genetic determinant of poor lung growth, excess lung function decline and occurrence of low lung function, respiratory disability and COPD within existing child and adult cohorts 2) generation of new data to fill gaps in knowledge on pre-conception and transgenerational determinants and risk factors 3) validation of the role of risk factors by integration of data from relevant disciplines, integration of data from the cohort-related population-based biobanks and exploitation of appropriate statistical techniques 4) generation of information on change in DNA methylation patterns to identify epigenetic changes associated with both disease development and exposure to specific risk factors 5) generation of a predictive risk score for individual risk stratification that takes account of the combined effects of factors that cause poor lung growth, lung function decline, respiratory disability, and COPD and 6) implementation of an online interactive tool for personalised risk prediction based which will be disseminated freely and widely to the population, patients and health care providers. The work will provide an evidence base for risk identification at individual and population level that can underpin future preventive and therapeutic strategies and policies.


Grant
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: PHC-05-2014 | Award Amount: 8.44M | Year: 2015

Arterial hypertension affects up to 45% of the general population and is responsible for 7.1 million deaths per year worldwide. Although a large therapeutic arsenal exists, blood pressure control is sub-optimal in up to two thirds of patients. Yet, even small increments in blood pressure are associated with increased cardiovascular risk, with 62% of cerebrovascular disease and 49% of ischemic heart disease being attributable to hypertension. Detection of secondary forms of hypertension is key to targeted management of the underlying disease and prevention of cardiovascular complications. Endocrine forms of hypertension represent major targets for stratified approaches of health promotion. They include a group of adrenal disorders resulting in increased production of hormones affecting blood pressure regulation: primary aldosteronism (PA), pheochromocytoma/functional paraganglioma (PPGL) and Cushings syndrome (CS). These diseases are associated with increased cardiovascular and metabolic risk and with diminished quality of life. This project will develop and evaluate an omics-based stratified health promotion program for patients with endocrine forms of hypertension. We will define specific omics profiles for patients with PA, PPGL and CS by integrating high throughput genetics, genomics and metabolomics data with phenome annotations through bioinformatics modelling. Established profiles will be validated as stratification biomarkers and applied to the screening of referred hypertensive patients for both stratifying primary forms of hypertension for effective and cost efficient therapy as well as improving identification of endocrine causes for curative treatment and prevention of cardiovascular and metabolic complications. Omics-based profiling should allow identification of patients with preclinical phenotypes along with those hypertensives that cluster into specific endocrine groups who may benefit from personalised treatment.


Grant
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: PHC-13-2014 | Award Amount: 5.98M | Year: 2015

The BIOCYCLE Project proposes to test and critically assess the benefits and risks of an innovative regimen for improving the treatment of Crohns disease (CD), a chronic immune-mediated inflammatory disease affecting the gastro-intestinal tract of an increasing number of patients. Currently, the combination of anti-TNF monoclonal antibodies and immunosuppressants used without interruption is the gold standard for treating CD. However, long treatments are needed which raise safety concerns and costs. For maintaining the same level of efficacy while reducing risks and costs, the idea of BIOCYCLE is to use a regimen based on Treatment Cycles characterized by alternating periods where both drugs are administrated and periods where only either anti-TNF or immunosuppressant is used. The central part of the Project will be a large-scale controlled multi-centric clinical study including 300 patients in EU and USA to test the feasibility of shifting from drugs combination used without interruption (control) to Treatment Cycles (experimental arms). Primary and secondary objectives of the clinical study have already been validated for generating the best qualitative and quantitative data on clinical outcomes, predictors of disease evolution and costs. In parallel, the Project will calculate costs-of-illness associated with the different regimens and will perform surveys among patients, caregivers and healthcare systems representatives to assess their readiness to include/support Treatment Cycles in the clinical practice. This will be the basis of a critical appraisal of Treatment Cycles and guidelines for helping caregivers to decide which treatment regimen best fits the specific needs of their patient. If proven, the benefits of Treatment Cycles for treating CD will be discussed with key-opinion leaders involved in the treatment of other immune-mediated inflammatory chronic diseases to support the evolution of disease-driven treatments towards needs-driven treatments.


Coronary artery disease (CAD) is the leading cause of death in high-income countries. Invasive coronary angiography (ICA) is the reference standard for the diagnosis of CAD and allows immediate therapy. However, only 40% of patients undergoing ICA actually have obstructive CAD and ICA has relatively rare but considerable risks. Coronary computed tomography (CT) is the most accurate diagnostic test for CAD currently available. CT may become the most effective strategy to reduce the ca. 2 million annual negative ICAs in Europe by enabling early and safe discharge of the majority of patients with an intermediate risk of CAD. To evaluate this, we propose the DISCHARGE project that will be implemented by a multinational European consortium. The core of the project is the DISCHARGE pragmatic randomised controlled trial. The primary hypothesis will be that CT is superior to ICA for major adverse cardiovascular events (cardiovascular death, nonfatal myocardial infarction and stroke) after a maximum follow-up of 4 years in a selected broad population of stable chest pain patients with intermediate pretest likelihood of CAD. The trial will include 23 clinical sites from 18 European countries ensuring broad geographical representation. Comparative effectiveness research of complementing work packages include gender-related analysis, systematic review of evidence, cost-effectiveness analysis, and health-related quality of life. DISCHARGE has the capability to influence current standards and guidelines as well as coverage decisions and will raise awareness among patients, health care providers, and decision-makers in Europe about the effectiveness and cost-effectiveness of coronary CT angiography.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: Fission-2010-3.2.1 | Award Amount: 7.04M | Year: 2011

Diagnostic radiation represents an indispensable, sometimes life-saving, tool in modern medicine. However, the growing use of computerized tomography (CT) is a topic of concern in radiological protection, especially for children and adolescents. Children are generally more sensitive to the carcinogenic effects of ionizing radiation than adults. In addition, they have a longer life-span to express any effect and, because of their smaller mass, they may receive higher radiation doses from a CT scan than an adult. A large-scale multinational collaborative study will be set up with the objective of providing guidance towards optimisation of doses from paediatric CT scans. We have the following specific aims: 1) describe the pattern of use of CT in different countries and over time; 2) derive individual estimates of organ doses ; 3) assess biological markers of CT-irradiation effects; 4) directly evaluate radiation-related risk of cancer following CT; and 5) characterize the quality of CT images in relation to the estimated doses in order to better inform CT imaging practice. Scientists from nine European countries with expertise in epidemiology, clinical practice, radiology, dosimetry, biology and public health will contribute to the project with the objective of provide recommendations for a harmonized approach to CT dose optimisation for paediatric patients in Europe. Results of this research will serve to increase awareness of the scientific and medical communities about public health aspects related to the use of diagnostic radiation and to provide recommendations on the use of valuable diagnostic tools, with lowering the risk of its potential hazards as much as possible.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2011.2.4.1-2 | Award Amount: 3.96M | Year: 2012

About 75% of advanced epithelial ovarian cancer (EOC) patients respond to first-line surgery and chemotherapy but most relapse and ultimately acquire platinum resistance which soon leads to death. Relapsed high grade serous ovarian cancer (HGSOC) is the single main cause of EOC-related morbidity and mortality (despite the fact that HGSOC is highly chemosensitive). We hypothesize that the primary tumour includes a small population of resistant cells that are ultimately responsible for relapse and that by targeting this population front-line we may prolong disease-free survival or even achieve cure. OCTIPS will use unique retrospective and novel prospective paired tumour samples collected at the time of diagnosis and relapse to identify and validate molecules and pathways responsible for relapse. This identification will employ cutting edge high throughput multiplatform analyses such as next generation sequencing, mRNA and miRNA expression arrays and SNP array. Known and newly defined molecules or pathways will be evaluated in innovative integrated cancer model systems, utilising cell lines and avian egg and murine xenografts. New therapies to target these molecules and pathways will be developed and validated in these model systems. In order to translate these findings into patient benefit, agents that target the relapsing cell population will be tested for tolerability, efficacy, ability to combine with first line chemotherapy and then in randomised first line trials by the OCTIPS consortium. By translating the clinical observation of treatment failures into innovative cancer models that mimic relapsed ovarian cancer, we will validate improved front-line therapeutic strategies to help prolong patient survival. The impact of this application is that it defines a highly rigorous approach to integrate the bedside to bench to bedside paradigm, leading to novel prognosis-changing strategies for the treatment of ovarian cancer patients.


Grant
Agency: Cordis | Branch: FP7 | Program: CSA-CA | Phase: SiS-2009-1.1.2.2;SiS-2009-1.2.1.1 | Award Amount: 906.08K | Year: 2011

EURECNET is a network that brings together national REC associations, networks or comparable initiatives but also other bodies relevant in the field of research involving human participants like National Ethics Councils and the European Commissions ethical review system. Such a network forms the infrastructural basis to promote awareness of specific working practices of RECs across Europe, to enhance the shared knowledge base of European RECs, to support coherent reviews and opinions and to meet new challenges and emerging ethical issues. The central objective of EURECNET as a Coordinating Action is to foster the already existing network of European REC networks (in short EUREC). In particular, the contribution of EURECNET aims at five different levels: - fostering a sustainable infrastructure for European RECs (including a statute and a secretariat) to promote exchange and cooperation and to allow for international cooperation; - gathering information on RECs in Europe to build a basis for mutual exchange - collecting and evaluating training materials for REC members to enhance the quality of review; - conducting capacity building to facilitate the development of national REC networks (as future partners of EUREC); - identifying emerging ethical issues to develop common solutions for challenges posed by new technologies and scientific methodologies.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-CSA-Infra | Phase: INFRA-2010-1.1.13 | Award Amount: 13.42M | Year: 2011

The objective of this project is the integration of world class high-throughput sequencing and genotyping facilities that will provide sequencing and genotyping technologies and data analysis methodologies to the scientific community. The European Sequencing and Genotyping Infrastructure (ESGI) will enable external users to generate data rapidly and to acquire knowledge efficiently. By providing access to the ESGI facilities in order to benefit from the sequencing and genotyping technologies, there will be an outreach and sustainable impact for the scientific community in the area of biological and medical research to generate new knowledge. The ESGI will optimise European research programs and foster transnational collaborations. In general, the ESGI will defragment and thereby strengthen the European research capacities in genetics and genomics and improve the knowledge transfer from large genomics centers among themselves and to external expert groups or scientists who are focusing on specific research questions. Our aim is to apply and improve new high-throughput nucleic acids analysis technologies for a broad range of genetic and systems biology studies using well-phenotyped samples, for example those derived from standardised European biobanks and animal facilities. In particular, massively-parallel sequencing technologies are essential components of modern biomedical research and are ready to reveal molecular and cellular pathways underlying complex traits and common diseases. As the European Strategy Forum for Research Infrastructures (ESFRI) pointed out in the past, the development of an efficient infrastructure for sequencing and genotyping is of crucial importance to position Europe as one of the world-leading regions for genetics, genomics and systems biology research and thus a contribution to the European Research Area.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2009-4.2-1 | Award Amount: 7.36M | Year: 2010

Second-generation antipsychotics are increasingly being prescribed to children and adolescents. Their use, however, is mostly off-label, and adequate and sufficient data about efficacy and particular safety are lacking. This proposal focuses on two indications, the use of risperidone in children and adolescents with conduct disorder who are not mentally retarded, and the use of risperidone in adolescents with schizophrenia. The objectives are to 1) perform a series of clinical studies that will provide sufficient information for a Paediatric Use Marketing Authorisation to be obtained for these indications; 2) address scientific questions about the moderating and/or mediating factors of the efficacy and safety of risperidone in children and adolescents, and 3) disseminate the knowledge acquired by the proposed studies to medical and mental health professionals, to patients and their families and society in general.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH-2009-2.2.1-3 | Award Amount: 14.90M | Year: 2010

OPTiMiSE (OPtimization of Treatment and Management of Schizophrenia in Europe) will focus on two goals: optimising current treatments in Schizophrenia and explore novel therapeutic options for schizophrenia. The project intends to both address basic, but so far unanswered, questions in the treatment of schizophrenia and develop new and experimental interventions. It is expected that the project will lead to evidence that is directly applicable to treatment guidelines, will explore the development of novel treatments and will identify potential mechanisms for new drug development. To achieve these goals we have assembled a European team of experts that is second to none in the world. Together we will pursue the following objectives: -To use MRI to optimise treatment outcome and to facilitate prediction of response to treatment; - To provide a rational basis for antipsychotic choices in the treatment of first episode schizophrenia or schizophreniform disorder; - To improve functional outcome and reduce drug discontinuation by means of psychosocial interventions. - To explore the potential of cannabidiol CBD, a modulator of endocannabinoid functioning, as an alternative to D2 based antipsychotics - To validate a new approach to improve cognitive performance in patients with cognitive deficits on the basis of their genetic make up; - To use theoretically driven neurochemical imaging (MRS) and empirically driven genetic/genomic markers as predictors of response to treatment.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: NMP.2013.1.2-2 | Award Amount: 13.07M | Year: 2014

Increase in antibiotic resistance is a global concern worldwide. The project NAREBs main objective is the optimization of several nanoformulations of antibacterial therapeutics in order to improve the therapy of multi-drug resistant (MDR) tuberculosis (TB) and MRSA infections in European MDR patients. NAREB will address the problem of drug bioavailability inside the infected macrophages, transport across the bacterial cell wall, and avoidance of escape mechanisms (expressed by the pathogen). The success of the utilization of nanoparticles in the improvement of drug targeting in other diseases opens the way for novel applications in nanotechnology-based treatments aimed at controlling MDR-TB and MRSA. Specific objectives to achieve the main goal are: (i) Screening of different combinations of antibiotic drugs (small chemical molecules and/or biomacromolecules - glycopeptides) with nanocarriers (lipid, polymeric, biopolymeric); (ii) Loading of Transcription Factor Decoys (TFDs) designed to block the expression of essential bacterial genes in compatible nanoparticle systems and their testing as novel antibacterials; (iii) In vitro and in vivo testing of the best therapeutic combinations in relevant experimental models and using innovative bioimaging; (iv) Improved formulations of multifunctional particles containing selected antibiotics and TFDs for increasing the bioavailability of active molecules in the site of infection (targeting strategy, adapted route of administration) (v) Assessing safety, regulatory and production (GLP/GMP) aspects in relation with the most promising nanoformulations; (vi) Clinical Development Plan for the preparatory work for the subsequent clinical testing of the selected nanoformulations. The project NAREB brings together 15 partners (including 4 SMEs and 1 industry) from 8 EU Member and Associated States with outstanding complementary expertise, ranging from material engineering to molecular biology, pharmacology and medicine.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2011.1.4-1 | Award Amount: 7.64M | Year: 2012

Treating Rheumatoid Arthritis (RA) is a crucial challenge for the health systems. RA is the most common inflammatory arthritis, affecting 0.5% to 1% of the general population worldwide with little variation of the prevalence among countries. The current pharmacological management of RA involves early intervention with synthetic disease modifying anti-rheumatic drugs (DMARDs) either singly or in combination. Despite all those treatments, RA remains as an unmet clinical need where several concerns about long term treatments based on biologics have been arisen (Bongartz, 2009) while there are still approximately 20-40% of rheumathoid arthritis patients that do not have an adequate response to anti-TNF (Vander CB, 2006). The preclinical data obtained by the REGENER-AR consortium in a RA efficacy model in mice using allogeneic eASCs by intravenous route, demonstrated that mesenchymal expanded adult stem cells (eASC) extracted from adipose tissue have a large potential for treating RA. REGENER-AR consortium has defined a clinical translational project which aim is to develop a broadly available and clinically applicable treatment for RA by exploiting the biology of living human eASCs. To do that, the consortium is developing an Advanced Therapy Medicinal Product (ATMP) based on allogeneic eASCs for the treatment of RA (product internal code, Cx611) and ready for starting the clinical research (IMPD and clinical protocol has been approved by the regulatory agencies in January 2011). To accomplish this goal, it will be necessary to test this product through a phase Ib/IIa clinical trial in order to define the safety and feasibility of the systemic administration of allogeneic eASCS in patients with RA, but it will be necessary as well to advance in the difficulties that prevent cell therapy to be considered as a largely available product in the market facing several issues related to the production scale-up, effectively clinical treatment and regulatory affairs compilance


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2012.1.4-1 | Award Amount: 8.01M | Year: 2013

In renal allograft recipients, 10-year graft survival has not improved over the past decades. Histological examination of graft biopsies has long been the gold standard to confirm graft injuries, but biopsies are invasive and histological grading is not very robust. There is thus a need for robust, non-invasive methods to predict and diagnose acute and chronic graft lesions, to improve patient treatment, quality of life and long-term graft survival. Also, there is an unmet need for better understanding of the immune and non-immune mechanisms of interstitial fibrosis /tubular atrophy and graft loss. Combining all the skills required to build upon previous findings, BIOMARGIN will offer such opportunities in renal transplantation by integrating several omics approaches (mRNA, miRNA, peptides, proteins, lipids and metabolites) in blood, graft tissue and urine, in a well thought out, multistage discovery-to-validation translational programme, following the highest European ethics and regulatory requirements, as well as quality controls and quality assessments at all clinical and analytical steps. It is probably one of the first programmes to pursue such an integrated and systematic research approach. BIOMARGIN aims to: (i) discover, select and validate blood and/or urine biomarkers of renal allograft lesions in adult and pediatric kidney transplant recipients; (ii) provide renal transplant physicians with non-invasive, robust diagnostic tests and interpretation algorithms enabling closer, more accurate, more predictive and/or less invasive monitoring of transplanted patients; (iii) help to avoid or diminish the use of biopsies and improve patient treatment, quality of life and long-term graft survival; (iv) help understand the mechanisms involved in the allograft injury processes which, combined with mass spectrometry imaging should offer pathologists new molecular targets and tools for renal graft biopsy analysis.


Grant
Agency: Cordis | Branch: H2020 | Program: CSA | Phase: INFRADEV-03-2016-2017 | Award Amount: 3.30M | Year: 2017

Childrens health is a major societal challenge for Europe and the world, requiring development of paediatric medicines and treatments strategies based on evidence derived from clinical trials demonstrating efficacy and safety in infants and children, rather than on uncritical extrapolation from adult data (over 50 % of the medicines used for children had not been tested in this specific age group). Conducting clinical trials in children requires specific competences and infrastructure. ECRIN-ERIC (www.ecrin.org) is a generic infrastructure for multinational trial management, in any disease area. However it does not specifically address the paediatric needs in terms of trial management capacity. In its 2016 Roadmap, ESFRI suggested an upgrade of ECRIN to develop a common infrastructure for paediatric trial management through cooperation with the European Paediatric Clinical Trial Research Infrastructure (EPCTRI). The resulting PedCRIN project is also a unique opportunity to improve ECRIN business model and financial sustainability, attracting more industry-sponsored trials and more Member and Observer countries. PedCRIN builds on five work packages : project coordination (WP1); establishment of a strategy and upgrade of the governance and business plan, through a Sustainability Board jointly involving the scientific partners and the government representatives (WP2); development of tools specific for paediatric and neonatal trials (WP3) (methodology, outcome measures, adverse event reporting, bio-sample management, ethical and regulatory database, monitoring, quality and certification); operational support provided as transnational access to a few pilot trials to test the updated organisation and tools (WP4); communication targeting users communities (including industry), policymakers, patient and parents empowerment (WP5). Two other ESFRI-landmarks, BBMRI-ERIC and EATRIS ERIC, will contribute to PedCRIN.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH-2009-2.1.1-1 | Award Amount: 13.70M | Year: 2010

Genetic studies in model organisms and humans, including human genome-wide association studies, have pinpointed genomic regions that contribute susceptibility to common disease. However, to date, these data have provided limited insights into the genes, molecular pathways and mechanisms underlying disease pathophysiology. The EU FP6 Euratools consortium has been a remarkable success that established significant research collaborations, expertise and infrastructure in the EU, making a major contribution to the rat focus issue of Nature Genetics (Volume 40, May 2008), which featured six papers from the consortium. These successes underpin the current project in which we will use state-of-the-art and emerging large-scale technologies and advanced computation in an expanded multi-disciplinary approach to identify gene networks and genomic mechanisms underlying common diseases. We will use the rat as a model system to identify the major functional pathways underlying human inflammatory, cardiovascular and metabolic, and behavioral disorders. Our consortium brings together world class investigators who will use next-generation sequencing technologies to generate genomic, transcriptomic and epigenomic datasets. To this, we will add cutting-edge, quantitative metabonomic and proteomic datasets to give significant depth of coverage, at multiple levels, across pathophysiological phenotypes. These datasets will be gathered, annotated and integrated in relational and dynamic models that will be used in comparative analyses to understand human gene function at the level of the molecule, cell, tissue and organism. These studies will lead to new insights into disease mechanisms, through an integrative, cross-disciplinary approach to understanding large-scale functional genomic datasets in rats and humans.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH-2009-2.1.1-1 | Award Amount: 16.03M | Year: 2010

Mutations in about 400 different genes have been associated with Cognitive Disorders (CD), such as mental retardation, autism, neurodegenerative disorders, and psychiatric disorders. Whereas CD impose a major medical and socio-economical problem, there are no systematic studies that aim to provide insight into common mechanisms in CD. We propose a systems biology approach to gain insight into common mechanisms leading to cognitive impairment: (1) Identification of genes involved in cognitive disorders. Despite considerable progress in the identification of genes underlying CD, the majority of causative genes in CD remain unidentified. Therefore, our first objective is to identify new genes causative of CD by implementing high-throughput strategies. (2) Elucidation of molecular networks that are commonly disrupted in CD. Recent genetic and neurobiological research revealed evidence for a number of molecular and cellular pathways that are shared by the various genetic CDs. Prominent examples are Rho GTPase-related genes and genes that regulate chromatin structure/function (epigenetics) associated with mental retardation and autism. Our second objective is to systematically explore this concept by elucidation of molecular networks using functional genomics strategies in genetic models that are the cornerstone of neuroscience, such as mouse and fruit fly. (3) Identify genetic modifiers and small compounds that modulate the disease phenotype. Our third objective is to resolve the molecular underpinnings of the large degree of clinical variability that is typical for all types of CD, even among patients carrying identical gene mutations. Genetic modifier screens in cultured primary neurons as well as in available Drosophila models for CD will be used to reveal phenotypically relevant genetic interactions and molecular networks. Moreover, drug screens shall be conducted in fly and cellular models for CD, which will lead to pharmacological rescue of mouse models.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2011.2.4.2-1 | Award Amount: 14.96M | Year: 2012

The consortium led by UKER and EuroHYP, the European Stroke Research Network for Hypothermia, proposes a large, multicentre clinical trial which will assess mild hypothermia as a novel treatment for ischemic stroke. Stroke is the second cause of death world-wide and the second cause of lost disability-adjusted life years in high-income countries. Stroke incidence rises exponentially with age, so its social and economic burden will grow with the ageing of the European population. Current treatment options for the 80 to 85% of all strokes due to cerebral ischaemia - around. 900,000 events in Europe every year, or one every 40 seconds - are extremely limited. Systematic review of experimental studies suggests that hypothermia is the most promising intervention identified to date. Therapeutic cooling is effective in reducing ischaemic brain injury following cardiac arrest, and hypothermia is therefore considered by experts the most promising treatment for patients with acute ischaemic stroke, next to reperfusion strategies. The EuroHYP-1 trial is a pan-European, open, randomised, phase III clinical trial which will assess the benefit or harm of therapeutic cooling in 1500 awake adult patients with acute ischaemic stroke. In addition to efficacy and safety, the economic impact of therapeutic hypothermia will be assessed, along with several sub-studies involving imaging, ultrasound, and biomarker methods. The investigators involved in the EuroHYP-1 consortium are leading European experts in statistical design and analysis, therapeutic hypothermia, imaging, health economics, ultrasound, biomarkers, and trial execution (implementation and monitoring). Moreover in addition to these academic experts the consortium also involves European patient and family advocacy groups and small and medium-size enterprises, and the joint endeavours of this extended team will ensure the successful enrolment of patients at eighty hospitals across 25 countries in Europe.


Parkinsons disease (PD) is a major, chronic, non-communicable disease and the 2nd most frequent neurodegenerative disorder worldwide. Excess iron is primarily detected in the substantia nigra pars compacta, where dopaminergic neurons are exposed to high levels of oxidative stress produced by mitochondrial disorders and dopamine metabolism. Our previous preclinical, translational and pilot clinical studies demonstrated that novel iron chelation therapy with the prototypic drug deferiprone (DFP) (i) induces neuroprotection in cell models of PD via a powerful antioxidant effect, (ii) reduces regional siderosis of the brain, (iii) reduces motor handicap via inhibition of catechol-o-methyl transferase, and (iv) slows the progression of motor handicap in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model and in early PD patients. This project now seeks to demonstrate that conservative iron chelation therapy with moderate-dose DFP (30 mg/kg/day) slows the progression of handicap in de novo PD patients while not affecting systemic parameters. The 9-month, parallel-group, randomized, placebo-controlled, multicentre trial will be followed by a 1-month wash-out period. The primary efficacy criterion will be the change in motor and non-motor handicap scores on the Total Movement Disorders Society Unified Parkinsons Disease Rating Scale to identify disease-modifying and symptomatic effects. The secondary efficacy criterion will be the change in score between baseline and 40 weeks (i.e. probing the disease-modifying effect only). Potential surrogate radiological and biological biomarkers, health economics and societal impacts will be assessed. 17 national, European and international research and innovation activities will be linked with the project. The study results should prompt academic and industrial research on iron chelation as a disease-modifying treatment in neurodegenerative diseases.


Grant
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: PHC-15-2014 | Award Amount: 6.00M | Year: 2015

Osteoarthritis (OA) is an incurable disease that has evaded pharmacological interference, biologic therapy or surgical intervention to prevent disease progression. Currently, OA is designated the 11th highest contributor (of 291 diseases) of global disability. In the absence of effective treatment options, cellular therapies using mesenchymal stem/stromal cells (MSCs) have emerged as potential candidates to overcome this clinical short-coming. Autologous adipose-derived mesenchymal stromal cells (ASCs) are attractive for cellular therapy given the abundance of tissue, high frequency of MSCs and minimally invasive harvest procedure. The EU consortium ADIPOA has shown in a first in man 2-centre Phase I safety study that intraarticular injection of a single dose of autologous ASCs to the knee (18 patients, 12 month follow-up) was well-tolerated, had no adverse effects, and resulted in an improvement in pain score and functional outcome. ADIPOA2 will deliver a large-scale clinical trial in regenerative medicine for OA. The purpose of the project is to design and implement a phase IIb study to assess the safety and efficacy of autologous (patient-derived) ACSs in the treatment of advanced OA of the knee. The cells will be prepared from samples of adipose tissue harvested from patients by lipoaspiration. ADIPOA2 will comprise a multi-centre, randomized clinical trial comparing culture-expanded, autologous adult ASCs in subjects with knee OA with another widely used therapeutic approach for knee degeneration (injection of Hyaluronan). There are two large elements of the study: (1) the production of consistent batches of high-quality autologous ASCs under GMP-compliant conditions and (2) delivery of these cell doses to patients in a trial which will meet all national and European regulatory and ethical standards and which will have sufficient statistical power to provide an unambiguous and definitive assessment of safety and efficacy.


Natoli G.,Italian National Cancer Institute | Andrau J.-C.,Aix - Marseille University | Andrau J.-C.,French Institute of Health and Medical Research | Andrau J.-C.,French National Center for Scientific Research
Annual Review of Genetics | Year: 2012

Mammalian genomes are extensively transcribed outside the borders of protein-coding genes. Genome-wide studies recently demonstrated that cis-regulatory genomic elements implicated in transcriptional control, such as enhancers and locus-control regions, represent major sites of extragenic noncoding transcription. Enhancer-templated transcripts provide a quantitatively small contribution to the total amount of cellular nonribosomal RNA; nevertheless, the possibility that enhancer transcription and the resulting enhancer RNAs may, in some cases, have functional roles, rather than represent mere transcriptional noise at accessible genomic regions, is supported by an increasing amount of experimental data. In this article we review the current knowledge on enhancer transcription and its functional implications. © 2012 by Annual Reviews.


Klatzmann D.,Paris-Sorbonne University | Klatzmann D.,French Institute of Health and Medical Research | Klatzmann D.,Biotherapy and Departement Hospitalo University Inflammation Immunopathology Biotherapy | Abbas A.K.,University of California at San Francisco
Nature Reviews Immunology | Year: 2015

Depletion of regulatory T (T Reg) cells in otherwise healthy individuals leads to multi-organ autoimmune disease and inflammation. This indicates that in a normal immune system, there are self-specific effector T cells that are ready to attack normal tissue if they are not restrained by T Reg cells. The data imply that there is a balance between effector T cells and T Reg cells in health and suggest a therapeutic potential of T Reg cells in diseases in which this balance is altered. Proof-of-concept clinical trials, now supported by robust mechanistic studies, have shown that low-dose interleukin-2 specifically expands and activates T Reg cell populations and thus can control autoimmune diseases and inflammation.


Bonnans C.,University of California | Bonnans C.,French Institute of Health and Medical Research | Chou J.,University of California | Chou J.,University of California at San Francisco | Werb Z.,University of California
Nature Reviews Molecular Cell Biology | Year: 2014

The extracellular matrix (ECM) is a highly dynamic structure that is present in all tissues and continuously undergoes controlled remodelling. This process involves quantitative and qualitative changes in the ECM, mediated by specific enzymes that are responsible for ECM degradation, such as metalloproteinases. The ECM interacts with cells to regulate diverse functions, including proliferation, migration and differentiation. ECM remodelling is crucial for regulating the morphogenesis of the intestine and lungs, as well as of the mammary and submandibular glands. Dysregulation of ECM composition, structure, stiffness and abundance contributes to several pathological conditions, such as fibrosis and invasive cancer. A better understanding of how the ECM regulates organ structure and function and of how ECM remodelling affects disease progression will contribute to the development of new therapeutics. © 2014 Macmillan Publishers Limited.


Patent
Sorin Crm Sas, French Institute of Health, Medical Research and Joseph Fourier University | Date: 2015-02-09

A device for treating sleep apnea by discriminating between successive sleep stages of a patient includes a generator configured to produce stimulation pulses, a stimulator that receives the stimulation pulses produced by the generator and delivers stimulation to the patient, a sensor configured to measure a biological parameter of the patient, and a controller. The controller is configured to determine a state of the patient based on the biological parameter, perform a sleep analysis based on the state of the patient, activate the generator to trigger production of the stimulation pulses, determine a variation of the biological parameter subsequent to the production of the stimulation pulses, determine a response of the patient to the stimulation pulses according to the variation of the biological parameter, and determine a sleep stage of the patient based on the response.


Patent
Sorin Crm Sas, French Institute of Health, Medical Research and Joseph Fourier University | Date: 2015-02-09

A device for treating sleep apnea in a patient through stimulation. The device includes a generator configured to produce stimulation pulses, a stimulator that receives the stimulation pulses produced by the generator and delivers stimulation to the patient, and a controller. The controller is configured to determine a sleep state of the patient, adaptively control the generator based on the sleep state where the sleep state includes a plurality of sleep stages, and modulate a stimulation energy of the stimulation pulses produced by the generator based on the sleep stage of the patient


Patent
Sorin Crm Sas, French Institute of Health and Medical Research | Date: 2015-07-22

An active implantable medical device for neurostimulation therapy is disclosed. The device produces stimulation pulse sequences generated continuously in succession during activity periods separated by intermediate inactivity periods during which no stimulation is issued. An input signal, provided by a physiological sensor, representative of cardiac activity and/or of the patients hemodynamic status is received by circuitry. The circuitry further provides for dynamic control of the neurostimulation therapy, wherein the length of activity periods is modulated based on the current value level of the control parameter compared to a threshold. The duration of the next period of inactivity is calculated by the circuitry at the end of each activity period to maintain a constant duty cycle ratio between periods of activity and periods of inactivity.


Patent
Institute Gustave Roussy, French Institute of Health, Medical Research, University Paris - Sud, University of Versailles and Assistance Publique Hopitaux De Paris | Date: 2014-01-27

The present invention concerns the V617F variant of the protein-tyrosine kinase JAK2, said variant being responsible for Vaquez Polyglobulia. The invention also relates to a first intention diagnostic method for erythrocytosis and thrombocytosis allowing their association with myeloproliferative disorders, or to the detection of the JAK2 V617F variant in myeloproliferative disorders allowing their reclassification in a new nosological group.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2012.2.1.1-1-B | Award Amount: 16.85M | Year: 2012

Neurodegenerative (ND) and neuromuscular (NM) disease is one of the most frequent classes of rare diseases, affecting life and mobility of 500,000 patients in Europe and millions of their caregivers, family members and employers. This NEUROMICS project brings together the leading research groups in Europe, five highly innovative SMEs and relevant oversea experts using the most sophisticated Omics technologies to revolutionize diagnostics and to develop pathomechanism-based treatment for ten major ND and NM diseases. Specifically we aim to: (i) use next generation WES to increase the number of known gene loci for the most heterogeneous disease groups from about 50% to 80%, (ii) increase patient cohorts by large scale genotyping by enriched gene variant panels and NGS of so far unclassified patients and subsequent phenotyping, (iii) develop biomarkers for clinical application with a strong emphasis on presymptomatic utility and cohort stratification, (iv) combine -omics approaches to better understand pathophysiology and identify therapeutic targets, (v) identify disease modifiers in disease subgroups cohorts with extreme age of onset (vi) develop targeted therapies (to groups or personalized) using antisense oligos and histone deacetylase inhibitors, translating the consortiums expertise in clinical development from ongoing trials toward other disease groups, notably the PolyQ diseases and other NMD. To warrant that advances affect a large fraction of patients we limited the selection to a number of major categories, some of which are in a promising stage of etiological and therapeutic research while some others are in great need of further classification. The efforts will be connected through a NEUROMICS platform for impact, communication and innovation that will provide tools and procedures for ensuring trial-readiness, WP performance, sustainability, interaction with the chosen Support IRDiRC and RD-Connect project and involvement of stakeholders in the NDD/NMD field.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2013.2.1.1-1 | Award Amount: 15.78M | Year: 2013

The aim of SYBIL is to carry out extensive functional validation of the genetic determinants of rare and common skeletal diseases and the age related factors contributing to these painful conditions. To achieve this goal SYBIL will gather complementary translational and transnational scientists, systems biologists, disease modellers, leading SMEs and industrialists that will perform in-depth characterisation (complete molecular phenotyping) of pre-clinical models (cellular and animal) for a variety of common and rare skeletal diseases. SYBIL will establish a systematic pipeline of in vitro, ex vivo and in vivo models of increasing complexity and will also make use of novel technologies such as iPS cells and exclusive Virtual Patient software to identify potential therapeutic targets for further validation through simultaneous modelling of fundamental and complex physiological pathways. SYBIL will rely on i) an Omics Knowledge Factory for systematically generating new knowledge on skeletal disease pathophysiology and to generate the relevant Omics profiles necessary to detect and validate new disease determinants, biomarkers and therapeutic targets for future clinical developments, and ii) a Systems Biology Hub to integrate the high-throughput and data-dense information, to gain a global understanding of pathophysiological commonalities between different skeletal diseases and recognize predominant shared pathways and mechanisms that may represent new targeted routes to treatment. SYBIL will also identify potential modifier genes and study the epigenome that will ultimately influence the timing and efficacy of new personalised treatments. Overall SYBIL achievements will tremendously boost the efficient pre-clinical assessment and development of therapeutics against skeletal diseases and thus indirectly reduce their social and healthcare burden.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2009-2.4.4-1 | Award Amount: 8.05M | Year: 2010

The Collaborative Project on Mendelian Forms of Parkinsons Disease (MEFOPA) will bring together the major groups in Europe with a track-record in basic and clinical research on rare Mendelian forms of Parkinsons disease (PD) in order to identify and validate relevant disease-related molecular pathways, drug-targets and biomarkers for disease susceptibility and progression.. Over the last years it has become increasingly clear that progress in the understanding of the molecular basis of PD, the second most common neurodegenerative disorder, and hence the chance to develop effective disease-modifying treatments, will most likely be brought about by focusing on the rare variants of the disease with known genetic defects. The groups forming the MEFOPA-consortium will therefore analyze the molecular pathways underlying inherited forms of PD with autosomal-dominant and autosomal-recessive inheritance in an integrative way, using cellular and animal models and cutting-edge technology. These two subprojects will provide targets for novel, disease-modifying treatment strategies. In a third subproject, a European registry and biobank for patients with rare Mendelian forms of PD will be established. Body fluids will be collected and systematically analyzed by unbiased proteomic techniques as well as by focussed analysis of candidate proteins, and ex vivo cellular models will be generated, in order to allow validation of disease-related alterations detected in the models analyzed in subprojects 1 and 2. Through this integrated, translational approach combining basic and clinical research groups, the project aims to achieve measurable progress in defining the relevant targets and readouts for disease-modifying therapies and will set the stage for rationally designed drug trials in carefully selected groups of patients and even presymptomatic mutation carriers.


Patent
French Institute of Health, Medical Research, Cea and University Paris - Sud | Date: 2014-09-17

The present invention relates to a lentiviral vector wherein the expressed integrase protein comprises at least one point mutation consisting of the substitution of the aspartic acid residue at position 167 by an amino acid selected from the group consisting of histidine, arginine and lysine.


Patent
French Institute of Health, Medical Research, Aix - Marseille University and Institute Jean Paoli & Irene Calmettes | Date: 2015-12-09

The invention relates to antigen peptide derived from the Nectin4 and its use for preventing and treating cancer.


Grant
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: PHC-03-2015 | Award Amount: 5.70M | Year: 2016

Hepatocellular carcinoma (HCC) is the most common liver malignancy, with an estimated 750,000 new cases and 695,000 deaths per year, rating third in incidence and mortality in the world. Whilst incidence and mortality for other cancers are declining, HCC represents an increasing public health problem in Europe with men having a higher incidence than women. Several liver diseases lead to HCC and become per definition co-morbidities, such as nonalcoholic steatohepatitis (NASH) or hepatitis B and C virus infection. Most patients die within one year of diagnosis and treatment failure reflects the heterogeneous nature of this tumour, highlighting the need to identify common and co-morbidity specific disease pathways for individualized therapy. HEP-CAR will focus on three leading HCC associated co-morbidities, specifically NASH and hepatitis B and C infection. Non-biased genetic and lipidomic screens will define cellular pathways that are deregulated in HCC and the impact of co-morbidities and gender. Next to established patient cohorts, several in vitro and in vivo models are available to evaluate the role of co-morbidities as drivers of host oncogenic pathways and to provide much needed pre-clinical models for mechanistic studies and future drug screening. We will develop new approaches to study the impact of co-morbidities on HCC immunobiology, ranging from state-of-art tissue explant models to novel humanized mouse models. The aim of HEP-CAR is to define host pathways that impact HCC pathogenesis and to assess their role in different co-morbidities and treatment responses. The research and clinical excellence will be combined with the knowledge transfer and communication competence of leading organizations such as the European Association for the Study of the Liver (EASL) and the European Liver Patients Association (ELPA). Thus, HEP-CAR will generate tangible and sustained improvements in the understanding, prevention and management of HCC for all European citizens.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH-2009-2.1.1-1 | Award Amount: 15.31M | Year: 2010

In recent years, the zebrafish has emerged as a new vertebrate model organism for biomedical research which offers a unique combination of traits: a short generation time, small size and efficient breeding procedures make it the best choice among vertebrates for forward genetic screening and small-molecule screens, including toxicology, while the transparent embryo and larva offers unique opportunities for imaging of cell movement and gene expression in a developing organism. Building on recent advances in the zebrafish field, we will conduct high-throughput phenotyping of at least a thousand regulatory genes relevant for common human diseases, by behavioural assays (for viable mutants), 3D / 4D imaging and expression profiling (including high-throughput sequencing). We will include mutants generated by TILLING and by the new zinc finger nuclease method, as well as mutants from earlier forward-genetics screens. A phenotyping effort of this scale has never been undertaken before in any vertebrate organism. Complementing the study of mutants relevant for neurological disorders, we will produce an atlas of gene expression in the brain, the most comprehensive one in a vertebrate. We will further perform a genome-wide characterisation of regulatory elements of potential disease genes by a combination of bioinformatics and transgenics. Small-molecule screening for mutant rescue or disease-relevant processes will identify candidate drugs and provide insights into gene function. Our increasing knowledge on the regulators and their interactions with regulatory targets will be integrated with knowledge at cellular and organismic level. By capitalising on the virtues of the zebrafish system, this systems biology approach to the regulome will gain unique knowledge complementing ongoing work in mammalian systems, and provide important new stimuli for biomedical research.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2012.2.1.1-2 | Award Amount: 17.67M | Year: 2013

As more people survive into old age, the prevalence of heart failure (HF), one of the most common and debilitating diseases in older people, will rise still further. Delaying or preventing HF will have great benefit to those at personal risk, their families, society and the economy. HOMAGE aims to provide a biomarker (BM) approach that will a) help identify i. patients at high risk of developing HF before the onset of symptoms and ii. subsets of patients who are more likely to respond to specifically targeted therapies (personalized medicine). In available cohorts, we will identify the most promising omics-based BM profiles for the pre-symptomatic diagnosis and future prediction of HF in patients at risk. The predictive value of the BMs for other co-morbidities commonly associated with HF and ageing will also be investigated. Furthermore, in a prospective trial, we will investigate the potential for targeting preventive therapy at patients with the greatest likelihood of response and the lowest risk of adverse effects. Our selection of innovative omics-based BMs is based on knowledge of biological pathways of the disease, which may facilitate identification of Biotargets for future therapies. On the economic side, HOMAGE will act as an economic catalyst for European SMEs in the field of cardiovascular and ageing BMs, estimated to peak annual turnovers of up to 800 M.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2012.2.1.1-2 | Award Amount: 15.18M | Year: 2013

The ageing of the European population represents a rapidly rising social and economic challenge. Especially cardiovascular morbidity increases with age, but unfortunately, elderly patients are often difficult to diagnose due to confounding factors, leading to uncertainties in clinical decision making with huge impact on patients outcomes. Hence, there is an unmet need for novel biomarkers for more accurate diagnosis, risk assessment, and clinical outcome prediction for both acute and chronic cardiovascular diseases in the elderly. The BestAgeing consortium aims to improve this lack of diagnostic capabilities by developing and validating innovative omics-based biomarkers particularly for elderly patients supporting healthy ageing in Europe. Our study design addresses the most frequent and severe cardiovascular diseases of elderly patients by incorporating the appropriate disease cohorts and biomaterials from European populations. We aim to develop new omics-assays to diagnose cardiovascular disease, estimate risk, and monitor the response to treatment in elderly. This is envisaged to enable a more stratified and economic delivery of medicine. We expect that BestAgeing will generate novel European medical technologies that can improve the efficacy and efficiency of our care for elderly patients, which will also impact on socioeconomic wealth in Europe.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.1.3-3 | Award Amount: 7.70M | Year: 2013

The goal of SYMPATH is to advance clinical development of therapeutic vaccines targeting -synuclein (aSyn)-driven neurodegenerative diseases (ND). It addresses Parkinsons disease (PD) and multiple system atrophy (MSA), two synucleopathies, for which no causal therapy exists. Ultimately, both lead to patient disability and death, which along with patient number (PD) and age of onset (MSA, PD) define their high medical need status. The proposed programme focuses on 2 vaccine candidates, PD01A and PD03A, delivered by the innovative AFFITOME technology. Both are peptide-protein conjugate vaccines and first-in-class candidates. They were selected to elicit antibodies neutralizing aSyn but sparing compensatory -synuclein. Pre-clinical evaluation confirmed their disease-modifying activity in various models. The unprecedented clinical approach, called TANDEM strategy, uses the synergy resulting from applying 2 vaccine candidates in 2 complementary indications linked through their pathology. TANDEM PD/MSA capitalizes on (i) excellent clinical research centres and their associated national/European networks, (ii) platform methods assessing aSyn species as candidate biomarkers and (iii) preliminary clinical experience with PD01A, the first aSyn targeting vaccine ever tested in humans. Its core is formed by 2 phase I studies testing PD01A in MSA and PD03A in PD/MSA. Importantly, trial design (duration, endpoints, vaccine dose and schedule) will ensure collection of initial biomarker data connecting clinical results of PD- and MSA trajectories. SYMPATH defines the logical next development step of both AFFITOPE vaccine candidates for synucleopathies and generates information/material (biobank) rendering them more amenable to rational drug development. Successful completion of the programme promises reaching aSyn pathology with an active vaccine as a causal therapy for PD/MSA, thus advancing one or both candidates as prime targets for product development and investment.


Grant
Agency: Cordis | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2016 | Award Amount: 2.58M | Year: 2016

This ITN will train 10 ESRs to meet the urgent need for translation of Auditory Neuroscience into commercial and pharmaceutical products to treat hearing disorders including tinnitus. Tinnitus is the debilitating perception of imaginary sound that is often associated with hearing loss. This Liaison in Scientific Training for European auditory Neuroscience (LISTEN) is a consortium of top hearing scientists in industry and academia, who specialize in hearing mechanisms and translation to commercial applications, enabling broad career opportunities for our ESRs. The multidisciplinary training environment includes leading labs and companies from 7 EU states, specialized in research, drug and instrumental development. Hearing is vulnerable to noise trauma, medication and aging, and in the future hearing loss will be one of the top ten disease burdens for Europe. Europe must rapidly exploit academic knowledge to invest in treatments for hearing disorders including drug development. Young scientists entering this field must acquire a broad and detailed background in neuroscience, acoustics, biophysics and signal processing, and employ genetic, molecular, pharmacology, anatomy and imaging methods. No single European institute can encompass this, but together, our LISTEN network will enable young scientists and entrepreneurs to unravel hearing mechanisms and design the next-generation of treatments. Work Package 1 (WP1) focuses on neural coding of sounds from the cochlea to neocortex, including auditory processing for localizing sounds and complex cognitive tasks in both normal hearing and following hearing loss. WP2 will identify molecular and genetic mechanisms of the hyperexcitability underlying tinnitus, exploit new techniques for monitoring tinnitus and develop new drug therapies. Integration of the WPs will enable new insights into disease mechanisms and WP3 will provide the ESRs with an essential multidisciplinary background for their research and successful careers.


Grant
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: PHC-09-2015 | Award Amount: 28.14M | Year: 2016

Many HIV vaccine concepts and several efficacy trials have been conducted in the prophylactic and therapeutic fields with limited success. There is an urgent need to develop better vaccines and tools predictive of immunogenicity and of correlates of protection at early stage of vaccine development to mitigate the risks of failure. To address these complex and challenging scientific issues, the European HIV Vaccine Alliance (EHVA) program will develop a Multidisciplinary Vaccine Platform (MVP) in the fields of prophylactic and therapeutic HIV vaccines. The Specific Objectives of the MVP are to build up: 1.Discovery Platform with the goal of generating novel vaccine candidates inducing potent neutralizing and non-neutralizing antibody responses and T-cell responses, 2. Immune Profiling Platform with the goal of ranking novel and existing (benchmark) vaccine candidates on the basis of the immune profile, 3. Data Management/Integration/Down-Selection Platform, with the goal of providing statistical tools for the analysis and interpretation of complex data and algorithms for the efficient selection of vaccines, and 4. Clinical Trials Platform with the goal of accelerating the clinical development of novel vaccines and the early prediction of vaccine failure. EHVA project has developed a global and innovative strategy which includes: a) the multidisciplinary expertise involving immunologists, virologists, structural biology experts, statisticians and computational scientists and clinicians; b) the most innovative technologies to profile immune response and virus reservoir; c) the access to large cohort studies bringing together top European clinical scientists/centres in the fields of prophylactic and therapeutic vaccines, d) the access to a panel of experimental HIV vaccines under clinical development that will be used as benchmark, and e) the liaison to a number of African leading scientists/programs which will foster the testing of future EHVA vaccines through EDCTP


Patent
French Institute of Health, Medical Research, University Paris - Sud and University of Bordeaux 1 | Date: 2013-04-09

The present invention relates to polypeptides and their uses as apelin inhibitors. More particularly, the present invention relates to a polypeptide comprising the sequence as set forth in SEQ ID NO:1 wherein at least one arginine residue at position 18, 19, 22 or 23 has been substituted or deleted.


Patent
French Institute of Health, Medical Research, University of Strasbourg, French National Center for Scientific Research and Stichting Dienst Landbouwkundig Onderzoek | Date: 2012-05-04

The present invention provides materials and methods for DNA amplification, in particular linear amplification methods using RNA polymerase. These methods permit high-throughput sequencing of pictogram amounts of DNA and are of use in a range of applications including genome-wide profiling of transcription factors and epigenetic DNA and histone modifications, global transcript profiling, mapping of chromatin conformations, as well as for forensic use and archaeological studies.


Patent
Center Jean Perrin, French Institute of Health, Medical Research and University Dauvergne Clermont | Date: 2012-04-27

The present invention relates to a combination of a curcuminoid and a taxane for use in the treatment of a hormone-refractory prostate cancer (HRPC) in a patient in need thereof.


Grant
Agency: Cordis | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2015-ETN | Award Amount: 3.85M | Year: 2015

This ETN is embedded into an established international research programme; The European Research Initiative on Anaplastic Lymphoma Kinase (ALK)-related malignancies (ERIA; www.erialcl.net) is an existing and functional network of 13 partners, which will cosset and nurture a cohort of early stage researchers to become confident, competent, independent and well-connected European scientists with excellent career perspectives. ERIA was instigated to coordinate research into ALK-related malignancies to facilitate the development of less-toxic and more efficacious therapies. ALK is increasingly recognised as a prevalent oncogene in a number of human malignancies and therefore poses a prominent clinical problem, which requires coordinated research into its oncogenic mechanisms. ERIA now conducts a collaborative multidisciplinary research programme at the interface of biomedical and bio-mechanistic approaches, which will be an excellent environment to train the next generation of European scientists. The 15 recruited fellows will be incorporated into international academic study groups (all partners of the ERIA network) to perform high calibre research and also will be exposed to environments from other sectors to broaden their experience. Secondments will include technical training within individual laboratories and SMEs (TissueGnostics, Galkem, Cambridge Life Sciences, Sofigen and Varionostics) as well as large Pharma (Roche). Training through research will be complemented with a balanced programme of transferable skills and access to local courses. The training of each fellow will be guided by a personal career development plan and supervised by a PhD committee panel. The primary goal of the network is to train the recruited fellows by participation in an internationally competitive research programme and integrating them into an international network. Thereby providing competence in state-of-the-art research and development at the forefront of translational science.


Patent
French Institute of Health, Medical Research, Cea, University Paris - Sud and University Paris Diderot | Date: 2013-07-31

The present invention relates to the prevention or treatment of inflammatory diseases. The present invention also relates to a method for screening a compound capable of promoting or restoring the resolution of inflammation and which may be useful for preventing or treating inflammatory disorders.


Patent
French Institute of Health, Medical Research, University of Paris Descartes and University Paris - Sud | Date: 2012-10-29

The present invention relates to the treatment and the diagnosis of atherosclerosis, in particular to a miRNA for use in the treatment and the diagnosis of atherosclerosis.


Patent
French Institute of Health, Medical Research and University of Burgundy | Date: 2012-03-26

The present invention relates to a mutated heat-shock protein 110 (HSP110) lacking its substrate binding domain, which does not exhibit its chaperone activity and/or is not capable of binding to heat-shock protein 70 (HSP70) and/or to heat-shock protein 27 (HSP27), but which is capable of binding to a wild-type HSP 110. Such a mutated heat-shock protein 110 can be used (i) in methods for prognosing survival and/or the response to a treatment of a patient suffering from a cancer, more particularly from a cancer liable to have a microsatellite instability (MSI) phenotype, such as colorectal cancer (CRC), and (ii) for treating cancers.


Patent
French Institute of Health, Medical Research, Institute Jean Paoli & Irene Calmettes, Aix - Marseille University, University Claude Bernard Lyon 1 and Center Leon Berard | Date: 2016-05-26

The present invention provides antibodies directed against ICOS or a derivative thereof which neutralize ICOS engagement on Treg by inhibiting the fixation between ICOS and ICOS-L and abrogate proliferation of Treg induced by plasmacytoid dendritic cells. The present invention further provides antibodies directed against ICOS or a derivative thereof which induce IL-10 and IFN production, induce CD4+ T cells proliferation, reduce Tconv proliferation, and increase the immunosuppressive function of Treg.


Patent
French Institute of Health, Medical Research, Institute Gustave Roussy, Assistance Publique Hopitaux De Paris, Center Henri Becquerel, University of Paris Descartes, University Pierre, Marie Curie and University Paris - Sud | Date: 2016-06-08

The present invention concerns an in vitro method for diagnosing a myeloid tumour or a lymphoid tumour in a subject, which comprises the step of analyzing a biological sample from said subject by (i) detecting the presence of a mutation in the Ten Eleven Translocation protein family member 2 gene (TET2) coding for the polypeptide having the sequence SEQ ID NO: 2, and/or (ii) analyzing the expression of the TET2 gene; wherein the detection of such a TET2 mutation, of the absence of expression of TET2 or of the expression of a truncated TET2 is indicative of a subject developing or predisposed to develop a myeloid tumour or a lymphoid tumour.


Patent
Assistance Publique Hopitaux De Paris, French Institute of Health, Medical Research and University Paris - Sud | Date: 2012-06-21

The present invention relates to a method for detecting the presence of carbapenemase-producing bacteria in a sample, said method comprising the steps of: a) performing cell lysis on a test sample in order to obtain an enzymatic suspension; b) reacting a fraction of the enzymatic suspension obtained in step a) with a reagent kit, said reagent kit comprising a carbapenemase substrate selected from the group consisting of carbapenems and cephamycins, a pH color indicator which will change color when the pH of the reaction mixture is comprised between 6.4 and 8.4, wherein a color change after step b) indicates the presence of carbapenemase-producing bacteria in the test sample. The invention also relates to a reagent kit, to a microtiter plate and to their uses in detecting the presence of carbapenemase producers in a test sample.


Patent
Assistance Publique Hopitaux De Paris, Igr&D Sa, University Paris - Sud, Institute Gustave Roussy, University of Versailles, French Institute of Health and Medical Research | Date: 2013-02-15

The present invention concerns the V617F variant of the protein-tyrosine kinase JAK2, said variant being responsible for Vaquez Polyglobulia. The invention also relates to a first intention diagnostic method for erythrocytosis and thrombocytosis allowing their association with myeloproliferative disorders, or to the detection of the JAK2 V617F variant in myeloproliferative disorders allowing their reclassification in a new nosological group.


Patent
Sorin Crm Sas, University of Rennes 1, French Institute of Health and Medical Research | Date: 2016-06-28

One system includes a stimulation device such as a vagus nerve stimulation lead, and a controller for controlling the stimulation device according to a set of stimulation parameters. A memory of the stimulation device contains a state transition model, and for each state defines a set of stimulation parameters and at least one expected response during the application of stimulation with the parameters. A matrix determines the transition rules between states based on physiological levels measured versus target levels. A state transition control unit determines, in an organized timely method, possible transitions between states according to rules on the physiological levels obtained in response to the implementation of the stimulation parameters of the current state, and a transition from a current state to a new state causes a corresponding change in the parameter set used for stimulation.


Patent
Sorin Crm Sas, University of Rennes 1, French Institute of Health and Medical Research | Date: 2016-06-28

One system includes a stimulation device such as a vagus nerve stimulation lead, and a controller for controlling the stimulation device according to a set of stimulation parameters. A memory of the stimulation device contains a state transition model, and for each state defines a set of stimulation parameters and at least one expected response during the application of stimulation with the parameters. A matrix determines the transition rules between states based on physiological levels measured versus target levels. A state transition control unit determines, in an organized timely method, possible transitions between states according to the rules on physiological levels obtained in response to the implementation of the stimulation parameters of the current state, and a transition from a current state to a new state causes a corresponding change in the parameter set used for stimulation.


Patent
Sorin Crm Sas, University of Rennes 1, French Institute of Health and Medical Research | Date: 2016-06-28

One system includes a stimulation device such as a vagus nerve stimulation lead, and a controller for controlling the stimulation device according to a set of stimulation parameters. A memory of the stimulation device contains a state transition model, and for each state defines a set of stimulation parameters and at least one expected response during the application of stimulation with the parameters. A matrix determines the transition rules between states based on physiological levels measured versus target levels. A state transition control unit determines, in an organized timely method, possible transitions between states according to the rules on physiological levels obtained in response to the implementation of the stimulation parameters of the current state, and a transition from a current state to a new state causes a corresponding change in the parameter set used for stimulation.


Patent
Sorin Crm Sas, University of Rennes 1, French Institute of Health and Medical Research | Date: 2016-06-28

One system includes a stimulation device such as a vagus nerve stimulation lead, and a controller for controlling the stimulation device according to a set of stimulation parameters. A memory of the stimulation device contains a state transition model, and for each state defines a set of stimulation parameters and at least one expected response during the application of stimulation with the parameters. A matrix determines the transition rules between states based on physiological levels measured versus target levels. A state transition control unit determines, in an organized timely method, possible transitions between states according to the rules on physiological levels obtained in response to the implementation of the stimulation parameters of the current state, and a transition from a current state to a new state causes a corresponding change in the parameter set used for stimulation.


Patent
French Institute of Health, Medical Research, Aix - Marseille University, Institute Jean Paoli & Irene Calmettes and French National Center for Scientific Research | Date: 2014-06-05

The present invention concerns an oligonucleotide modified by substitution at the 3 or the 5 end by a moiety comprising at least one ketal functional group, wherein the ketal carbon of said ketal functional group bears two saturated or unsaturated, linear or branched, hydrocarbon chains comprising from 1 to 22 carbon atoms, and the use therefore as a medicament, in particular for use for treating cancer.


Grant
Agency: Cordis | Branch: FP7 | Program: CSA-CA | Phase: HEALTH-2012.2.3.1-1 | Award Amount: 2.50M | Year: 2012

This Coordination and Support Action proposal aims at aiding the implementation of the Joint Programming Initiative on Antimicrobial Resistance (JPIAMR). JPIAMR currently has 18 participating countries and organisations from 8 of these are active partners of the CSA consortium. This proposal describes in detail the different work packages (WPs) that have been suggested in order to secure the rapid implementation of JPIAMR as a mature European partnership. In summary, WP1 delivers the coordination and management needed for efficient operation, WP2 delivers a communication strategy to ensure that everyone in the field is made aware of JPIAMR. Efficient communication strategies will enable cooperation, which will be further explored in WP5 on stakeholders involvement. WP3 delivers an SRA, which WP4 will implement. Both of these steps will be done in close collaboration with WP5 to ensure that input from relevant stakeholders is taken into account. Finally, WP6 will enable a framework for the evaluation of the initiative as well as set the rules for IPR. By this, the aim of the JPIAMR to integrate relevant scientific fields across national borders and to create a common European research agenda with a shared common vision will be addressed.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2012.2.3.2-1 | Award Amount: 7.82M | Year: 2012

Acquired immune deficiency (AIDS), tuberculosis (TB) and malaria are the primary infectious diseases causing death world wide. In addition to these pathogens, 170 million people are infected with hepatitis C virus (HCV), which leads to chronic liver disease. Because of shared routes of transmission, HCV co-infection is recognized as a major cause of morbidity and mortality among HIV-1 infected persons. The epidemiology and clinical features of co-infected subjects are well documented, however, there is a paucity of basic scientific studies addressing the interactions between these pathogens. There is undoubtedly a complex interplay between pathogens and the host immune response. This was highlighted when the Merck HIV-1 vaccine trial was halted due to increased HIV-1 transmission amongst vaccine recipients with previous adenovirus infection, suggesting that immune responses specific for adenovirus vector antigens were detrimental. We propose that pathogen evasion and dysregulation of host immune responses plays a key role in co-infection associated morbidity. We will test this hypothesis by establishing in vitro and ex vivo co-infection model systems to study pathogen interactions and assess the effect(s) of co-infection on innate signalling and adaptive immune responses. We will develop new approaches to dissect pathogen interactions, ranging from the genesis of fluorescent labelled viruses to state-of-the-art tissue explant models and novel humanised mouse models. Translational studies of co-infected patients will ascertain pathogen-specific effects on innate and adaptive immune responses and the consequences for disease progression. It is imperative that such interactions are elucidated before proceeding with new prophylactic or therapeutic strategies aimed at curtailing pathogen transmission or disease progression in co-infected individuals. We specifically address the call of understanding the basic biology of co-pathogen interactions and immunity.


Grant
Agency: Cordis | Branch: H2020 | Program: CSA | Phase: HCO-17-2015 | Award Amount: 2.04M | Year: 2015

The overall aim of JPsustaiND is to support the development and extension of the capacities of the EU Joint Programming Initiative on Neurodegenerative Diseases, in particular Alzheimers (JPND). Since 2009 JPND has been operating on a very light management structure based on a simple Terms of Reference. Through this JPND has been able to set a common Strategic Research Agenda, and to deliver its first implementation plan that has allowed among other achievements, the mobilisation of approximately 100 million of additional funding between 2011 and 2015 to support transnational research programs. While progress has been pleasing to date, the implementation of JPND must now be scaled-up to further catalyse Member State commitments, and to formalize synergies between members and various partners. The immediate challenge therefore for JPND is to secure its long-term sustainability by Member States, to mobilize those which are not yet participating, and to increase its impact at the national level and globally. JPsustaiND thus aims at creating the dedicated structure responsible for long-term JPND management and implementation, and extension of JPND membership to EU Member States and other countries and initiatives not yet participating. To achieve this goal, the JPsustaiND partners, with the support of the JPND Management Board, will implement the following six workpackages: Coordination and Management; Long Term Sustainability; Capacity Extension; Alignment and Outreach; Communication and Advocacy; and Monitoring, Evaluation and Impact Assessment. JPsustaiND will implement a stronger global dimension of the JPND, and will avoid duplication of research and infrastructure investment at the national level. By supporting further coordination and integration of national research and innovation programmes with the JPND research strategy, in coherence with Horizon 2020 objectives, JPsustaiND is thus creating a dedicated European Research Area for neurodegenerative diseases.


Grant
Agency: Cordis | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2015-ETN | Award Amount: 3.83M | Year: 2016

Metabolic disorders are at pandemic levels. Based on recent estimates, ~50% of Europeans are overweight, 20% are obese and 10% have type II diabetes. Obesity and insulin resistance impact European health to the tune of 110 billion per year. These disorders have genetic, nutritional and lifestyle causes. However, the molecular mechanisms that link nutrients and lifestyle to gene activity and chromatin are poorly understood, and drug targets are only starting to be identified. Pioneering experiments by ChroMe labs now reveal how sugars, exercise, the gut microbiome and novel drugs regulate chromatin. These novel links promise to substantially improve our understanding and treatment of metabolic disorders. National governments and the EU invest major resources to address the burden of the metabolic syndrome. However, there is an urgent need for expert human capital able to dissect metabolic diseases, exploit new targets and establish innovative therapies. No local nor international program currently provides adequate training at this emerging interface of chromatin and metabolism. ChroMe establishes a timely and intersectorial ETN that exploits Europes strengths in epigenetics, physiology and medicine to translate our molecular knowledge of chromatinmetabolism interactions into therapies. Our ESRs receive advanced training in emerging technologies, bioinformatic and translational approaches, and all engage in collaborative PhD projects co-supervised by academia and industry. ChroMes extensive transferable skills, dissemination and public engagement program equips our ESRs with the experience and personal network needed for a career in metabolic health. By systematically involving the non-academic sector at every level in our research, training and management, ChroMe will craft future European leaders with the necessary knowledge and skills to fight the metabolic syndrome pandemic.


Grant
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: PHC-14-2015 | Award Amount: 7.47M | Year: 2016

Severe combined immunodeficiency (SCID) is a devastating rare disorder of immune system development. Affected infants are born without functional immune systems and die within the first year of life unless effective treatment is given. Treatment options are limited to allogeneic haematopoietic stem cell transplantation and autologous stem cell gene therapy. Over the last 15 years, gene therapy for two forms of SCID (SCID-X1 and ADA SCID) has shown significant safety and efficacy in correcting the immunodeficiency and allowing children to live normal lives. Proof of concept of gene therapy for 3 other SCID forms has also been shown by members of the proposed SCIDNET consortium and is ready for translation into clinical trials. We are therefore in a position whereby, over the next 4 years, we can offer gene therapy as a curative option for over 80% of all forms of SCID in Europe. Importantly for 1 of these conditions (ADA SCID) we will undertake clinical trials that will lead to marketing authorisation of the gene therapy product as a licensed medicine. In addition, we will investigate the future technologies that will improve the safety and efficacy of gene therapy for SCID. Our proposal addresses an unmet clinical need in SCID, which is classified as a rare disease according to EU criteria (EC regulation No. 141/2000). The proposal also addresses the need to develop an innovative treatment such as gene therapy from early clinical trials though to a licensed medicinal product through involvement with regulatory agencies and is in keeping with the ambitions of the IRDiRC. The lead ADA SCID programme has Orphan Drug Designation and clinical trial design is assisted by engagement with the European medicines Agency. The ADA SCID trial will act as a paradigm for the development of the technologies and processes that will allow gene therapy for not only SCID, but also other bone marrow disorders, to become authorised genetic medicines in the future.


Grant
Agency: Cordis | Branch: H2020 | Program: CSA | Phase: INFRADEV-03-2016-2017 | Award Amount: 4.97M | Year: 2017

The INFRAFRONTIER RI integrates European Mouse Clinics and the European Mouse Mutant Archive with the common goal to ensure access to mouse models for basic research of human health and disease, and to translate this knowledge into therapeutic approaches for the benefit of the European society. The expanded INFRAFRONTIER2020 network, coordinated by the INFRAFRONTIER GmbH, includes 3 SMEs and is strategically responding to the INFRADEV3 call with aligned objectives to advance the long-term sustainability which are 1) development of business models and a stable legal framework; 2) raise awareness of the INFRAFRONTIER RI; 3) provide bespoke services aligned with user demands; 4) promote best practices in mouse phenogenomics; 5) enhance robustness of the INFRAFRONTIER IT infrastructure and use of the EMMA strain resource; and 6) improve business processes. Towards achieving these objectives key INFRAFRONTIER2020 project deliverables are: INFRAFRONTIER Business Plan2.0, and business models for all services Stable legal framework built on the INFRAFRONTIER legal entity INFRAFRONTIER annual stakeholder conferences Customised mouse model and secondary phenotyping pilot services INFRAFRONTIER advanced training schools in mouse phenogenomics Reengineered EMMA Database2.0 system Annotated mouse models of human diseases Quality management system for the legal entity INFRAFRONTIER2020 will 1) enhance the sustainable operation of the INFRAFRONTIER RI; 2) continue to structure the ERA, 3) foster innovation, and 4) address major societal challenges in human health by customised service pilots supporting research into common and rare diseases. A sustainable INFRAFRONTIER RI will ensure the quality of deposited mice and support the reproducibility of biological results. Outreach efforts will raise awareness of resources and services and facilitate sustainable engagement with industry and global consortia such as the International Mouse Phenotyping Consortium


Grant
Agency: Cordis | Branch: H2020 | Program: CSA | Phase: SC1-HCO-06-2016 | Award Amount: 2.04M | Year: 2016

In order to strengthen the sustainability and resilience of health services and systems a unique consortium of governmental and funding organizations plus research institutes, has expressed the ambition to systematically learn from the organisation of care in other settings. Overall objective of TO-REACH is to provide groundwork for an ERA-NET that will contribute to the resilience, effectiveness, equity, accessibility and comprehensiveness of health services and systems. We will do so along two work streams: A) We will develop a research program on cross-border learning from good (or even innovative) models of care and the conditions needed to transfer them to other settings for implementation. It could refer to anywhere in the care chain depending on the priorities as identified in a Strategic Research Agenda (SRA) within this project. Conceptual, methodological and empirical advancement will be achieved through 4 meta-questions that will instruct research under the ERA-NET, linking to what counts as good models of care, what are the conditions required for transferability, what are the conditions for up-scaling, and how do they contribute to the performance of health care organisations and systems. B) We will build a platform for funding organizations that allows for collaboration and coordination in the project and projected ERA-NET. This will synchronize priorities and activities, hence improving the quality and applicability of research with a focus on the topic areas as described under A. TO-REACH will pursue five specific objectives: Mapping health system challenges and priorities by synthesizing different materials and stakeholder inputs; Developing a framework and providing a knowledge synthesis on the above-mentioned meta-questions; Establishing sustainable cooperation of research funding bodies and links with other initiatives; Developing a SRA through agenda setting at European and Member State level; Disseminating the results of TO-REACH.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.1.3-2 | Award Amount: 7.95M | Year: 2013

TRANSLINK is a project devoted to assessing the mid-to long-term risk factors and improve the outcome of animal (bovine/porcine)-derived Bioprosthetic Heart Valve (BHV) implants. 300,000 patients/year benefit from BHV, a major healthcare problem (second most frequent cardiac surgery). BHV clinical outcome suffers from late dysfunctions restricting their application to older recipients. Based on a retrospective (already computerised) and prospective cohort of approximately 3,000 BHV recipients and control patients from 3 large EU cardiac surgery groups, TRANSLINK aims primarily to establish the possible role of recipients immune response (IR) against BHV as a major cause to mid- to-long term clinical dysfunction. Precise molecular analysis of preimplantation BVH sugar moieties will be performed. Possible indirect side-effects on BHV endocarditis and host vessels inflammation are secondary end points. Serial and trans-sectional blood samples will be dispatched to a battery of highly specialised partner groups for testing anti-Gal, -Neu5Gc and -hyaluronic acid antibodies (Ig) using both validated and newly designed screening tools, glycan array patterns, and macrophages/NK responses. Data will be crossed with clinical outcome scores. Project design aims at delivering comprehensive recommendations in the time-frame of the grant. Fundamental basic science progress in the field of carbohydrate antigens is also expected. Furthermore, prevention (BHV from engineered animal source lacking major antigens) and treatment (bioabsorbants of deleterious Ig) oriented remedies as well as prospective biomarkers of longterm BHV deterioration will be set up by three first-class SMEs. TRANSLINK may strongly impact the treatment of heart valve diseases by improving morbid-mortality in patients with heart valves diseases and increasing the indication of BHV to younger patients.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH-2009-2.2.1-2 | Award Amount: 15.03M | Year: 2010

The aim of EU-GEI is to identify the interactive genetic, clinical and environmental determinants involved in the development, severity and outcome of schizophrenia (EU-GEI, Schiz. Res. 2008; 102: 21-6). In order to identify these interactive determinants, EU-GEI will employ family-based, multidisciplinary research paradigms, which allow for the efficient assessment of gene-environment interactions. In order to go beyond old findings from historical convenience cohorts with crude measures of environmental factors and clinical outcomes, the focus in EU-GEI will be on recruitment of new, family-based clinical samples with state-of-the-art assessments of environmental, clinical and genetic determinants as well as their underlying neural and behavioural mechanisms. New statistical tools will be developed to combine the latest multilevel epidemiological with the latest genome-wide genetic approaches to analysis. Translation of results to clinical practice will be facilitated by additional experimental research and risk assessment bioinformatics approaches. This will result in the identification of modifiable biological and cognitive mechanisms underlying gene-environment interactions and the construction of Risk Assessment Charts and Momentary Assessment Technology tools which can be used for (i) early prediction of transition to psychotic disorder in help-seeking individuals with an at-risk mental state and (ii) early prediction of course and outcome after illness onset. In order to reach these goals, EU-GEI has assembled a multidisciplinary team of top schizophrenia researchers who have the range of skills required to deliver a program of research that meets all the calls requirements and who have access to / will collect a number of unique European samples. The partners in EU-GEI represent the nationally funded schizophrenia / mental health networks of the UK, Netherlands, France, Spain, Turkey and Germany as well as other partners.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2011.4.2-1 | Award Amount: 7.78M | Year: 2011

Dobutamine and adrenaline are widely used as second line therapy for systemic hypotension in infants. Dopamine is currently the most widely used first line drug. In neonates, sustained hypotension may, and impaired organ perfusion will, cause brain injury and poor neurodevelopmental outcomes. All three catecholamines are currently used off-label and have different modes of action which may result in potentially harmful haemodynamic effects. No reliable safety or efficacy data exists for the use of these drugs in neonates or newborns. Furthermore, no uniform criteria exist to define hypotension and there is little evidence to support current intervention strategies, which vary widely. Recently, superior vena cava (SVC) flow has been proposed as a more reliable indicator of circulatory failure than low blood pressure and preliminary results suggest Dobutamine is the optimum therapeutic in such cases. NEO-CIRC proposes 1) a randomised placebo controlled trial to provide safety and efficacy data for Dobutamine as a first line inotrope for all gestational ages 2) to perform pre-clinical; pharmacokinetic; pharmacodynamic; metabolomic and pharmacogenomic studies 3) to develop improved biomarkers of hypotension 4) to develop and adapt a formulation of Dobutamine suitable for newborns with the aim to apply for a Paediatric Use Marketing Authorisation. The NEO-CIRC consortium includes international experts in neonatal medicine, pharmacology, pharmacogenomics, drug formulation and pre-clinical neonatal models and an experienced group of experienced multicentre clinical trials NICUs. Outcomes anticipated include improved biomarkers of organ perfusion; a new consensus definition of neonatal circulatory failure and answers to key clinical practice uncertainties, including variability of response to Dobutamine in common pathophysiologies seen in newborn infants impact on longer term developmental outcomes so important to the patients, families and wider society.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2012.2.4.3-1 | Award Amount: 7.81M | Year: 2012

Current approaches to improving glycaemic control in type 1 diabetes are centered on increasingly complex insulin delivery systems. However, less than 30% of patients can achieve target levels of glucose control with this approach even in a clinical trial setting and many patients are either unable or unwilling to make the personal commitment required. By contrast, preservation of even small amounts of endogenous insulin production, has been shown to improve glycaemic control, reduce hypoglycaemia, improve quality of life and reduce long-term complications. Importantly, glycemic control in the presence of endogenous beta cell function is not demanding and hence would be effective across the full spectrum of individuals. Antigen specific immunotherapy (ASI) is the preferred approach to beta cell preservation since this avoids the risks of immunosuppression. Attempts at ASI to date although successful in preclinical models have had limited efficacy in humans. There is therefore an urgent need for the development of novel approaches to deliver effective ASI. Our Enhanced Epidermal Antigen Specific Immunotherapy (EE-ASI) system represents an innovative approach to ASI created by combining technologies brought by our academic and 2 SME partners. A beta cell target T cell epitope (proinsulin C19-A3) will be combined with the tolerogenic cytokine IL-10 and targeted to antigen presenting cells via gold nanoparticles and delivery into the very superficial layers of the skin using microneedles. Validation of manufacture, in vitro and in vivo preclinical efficacy will be demonstrated followed by a phase 1 clinical trial to confirm safety in humans. We anticipate that the EE-ASI system will be less costly, more effective and more acceptable to patients in improving glycaemic control than exogenous insulin replacement. Intellectual property, regulatory and ethical issues will be carefully addressed in order to maximise exploitation of this integrated system for the benefit of the SMEs.


Grant
Agency: Cordis | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2011-ITN | Award Amount: 3.95M | Year: 2012

Brain disorders impose an increasing economical and social burden in the member states of the European Union (EU). For most neurodegenerative diseases and many neuropsychiatric disorders no efficient treatment is available and no cure exists. In the next coming years the number of particularly elderly people suffering from brain disorders will tremendously increase. Predictions from the turn of the century about the exponential increase of dementia patients turned out to be correct and Alzheimers disease alone is underway to become the most expensive and most pressing health problem in the EU. The complexity of these diseases requires a more integrative view of the multiple interactions between genes and environment, synaptic processes and neuronal cicuitry. This is, however, not only achieved by training more young scientists in the relevant disciplines. The plastic properties of the brain can only be exploited by scientists that are trained to deal with this complexity and that are familiar with state of the art technology as well as with the principles at different levels of analysis. In consequence it is advisable for a training network to study more than one disease and to train scientists with a wide range of skills and background knowledge. The NPlast consortium consists of four partners from the private and seven partners from the public sector and will provide a research training program for fifteen young scientists. The program covers a broad spectrum of disorders and interventions ranging from synaptopathies and trafficking deficiencies to Alzheimers disease, and from altering gene expression programs to manipulations of the extracellular matrix of the brain to preserve or restore synaptic function. The key objective of the NPlast training network is to investigate neuroplastic principles that can preserve or restore function and that can be used to rejuvenitate the brain in the elderly as well as to treat neuropsychiatric conditions in adults.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-CSA-Infra | Phase: INFRA-2012-1.1.4. | Award Amount: 12.42M | Year: 2013

The mouse shows great similarities in development, physiology and biochemistry to humans, which makes it a key model for research into human disease. The major challenges for mouse functional genomics in the 21st century are to: Develop a series of mutant alleles for every gene in the mouse genome Determine the phenotypic consequences of each mutation Identify mouse models for the complete disease spectrum in humans To further develop and exploit the emerging mouse mutant resource, mouse models must be preserved and made available to the European biomedical research community. To this effect, the Infrafrontier-I3 project brings together the leading European centers for systemic phenotyping of mouse mutants and the European Mouse Mutant Archive network. The Infafrontier-I3 partners aim to meet the future challenges presented by phenotyping, archiving and disseminating mouse models in the ERA as follows: Contribute to resource development by archiving of 1215 new mouse mutant lines Provide free of charge Transnational Access to mouse production and 1st line phenotyping capacities Offer a specialized axenic service to produce, maintain and to distribute germ-free mice Provide user friendly accession of Infrafrontier services, extensive manual data curation and cross referencing with other mouse database Improve user services by developing novel phenotyping and cryopreservation SOPs and by refining innovative research instrumentation Engage with the user community using a wide range of PR activities, a dedicated user meeting and an industry liaison workshop Offer state of the art cryopreservation and phenotyping training courses Benchmark Infrafrontier services with other major repositories The comprehensive physical and data resources that will be generated by Infrafrontier-I3 will contribute to link basic biomedical research to medical applications and thereby drive innovation and support the Europe 2020 Strategy.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2010.2.1.2-1 | Award Amount: 16.86M | Year: 2011

Cancer is a complex disease involving multiple genetic and epigenetic events occurring, and influencing each other, over a long period of time. Understanding cancer, and ultimately developing effective targeted therapies, will therefore require that mutations and epigenetic alterations be systematically investigated during the multiple stages of disease development, from identifiable pre-neoplastic phases to overt cancer. Until now, no systematic effort has been undertaken to investigate these multiple layers of genome organization and function during cancer development. MODHEP aims at providing a 360 understanding of liver cancer, one of the most common types of tumors and, because of the homogeneity of the hepatic tissue, the most experimentally tractable one. The consortium brings together elite European scientists in the fields of genetics, chromatin regulation, genomics, liver cancer, computational and systems biology. This combination of skills will allow us to investigate and model at unprecedented resolution the chain of events leading from environmental perturbations and the occurrence of driver mutations to preneoplastic disease and cancer. Our experimental plan reflects some grounded assumptions: 1. cancer cannot be modeled without detailed information on the preneoplastic stages of disease; 2. genetic heterogeneity in humans would make systems-level modeling non realistic from a practical point of view. Both of these limitations are bypassed by the use of well-defined mouse models, followed by evaluation of the main conclusions in clinical samples; 3. many early stage driving events in cancer represent epigenetic alterations, which are invisible to classical genetic analysis, and are confounded by secondary and tertiary events in established tumors. Our approach will enable the identification of therapeutically relevant early-stage genetic and epigenetic alterations and the definition of their interplay in tumor development and maintenance.


Grant
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: PHC-16-2015 | Award Amount: 5.99M | Year: 2016

Chimeric antigen receptors (CARs) are artificial surface receptors that can be introduced into somatic cells by genetic engineering and that act as recognition molecules like antibodies or T-cell receptors. In this respect, CARs are increasingly used for cellular therapy to redirect T-cells specifically towards killing of cancer cells. Recent success stories of cancer therapy with CAR modified T-cells have raised enormous scientific and public expectations to cure severely ill patients. However, there are still many obstacles to overcome for translation into clinics because the technology for GMP-compliant manufacture of genetically modified cellular products is extremely complex and expensive. Moreover, CAR therapy needs to be improved with respect to off-target activity, safety and potency. Consequently, the envisaged project is overall aiming at a particular technological breakthrough in cellular cancer therapy by delivering a comprehensive CARAT platform explicitly tailored for automated, easy-to-handle and cost-efficient manufacture of CAR-modified ATMP. Specifically, we aim: (a) to implement unique next-generation cell processing tools like the CliniMACS Prodigy (b) to develop advanced enabling technologies to obtain more effective and safer cellular products by improved gene delivery and innovative CARs design (c) to assemble tools and technologies towards an integrated CARAT process for automated GMP-compliant manufacture of gene-modified T-cells (d) to demonstrate proof-of-concept and regulatory compliance (e) to disseminate broadly applicable, simplified CAR T-cell technologies In summary, our vision is to overcome current hurdles for translation of cellular therapies and to elevate them to the next level of standard-of-care thus serving patients with so far incurable solid tumours and hematologic malignancies. Thereby, we will empower Europe to become a global leader in the development and commercialisation of CAR T-cell tools and technologies.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH-2009-2.1.1-2 | Award Amount: 13.75M | Year: 2010

The International Cancer Genome Consortium (ICGC) has the goal of obtaining a comprehensive description of genomic, transcriptomic and epigenomic changes in 50 different tumour types and/or subtypes, with the aim of elucidating the genomic changes present in the many forms of cancers that contribute to the burden of disease throughout the world. We present a proposal for a European contribution to this effort through application of state-of-the-art approaches to the genomics of the most common form of renal cell cancer (RCC). RCC is of particular importance within Europe where the highest global incidence rates are observed. Disease incidence has increased over the last two decades, and it is now the 8th most common cancer in the EU. CAGEKID brings clinical and epidemiological resources that are unique worldwide together with the necessary genetics and genomics expertise required for this effort. In the first phase of the study, we will provide a full genomic characterisation of 100 matched pairs of DNA extracted from the tumour and constitutional samples. DNA will be completely sequenced, and the data brought together with those from whole genome transcript and methylation analyses. Follow-up studies of potential targets will be made in further samples. The results acquired will be relied to targeted protein analyses. The primary data will be made available to the scientific community, and the programme will contribute to establishing norms for the manipulation and storage of biological samples. CAGEKID will provide the first systematic analysis of this tumour site providing new insights into disease aetiology with application for diagnosis and treatment. It addresses a major need to identify new biological markers for renal cell cancer, one of very few tumour types for which there are currently no biological markers in routine clinical use. Renal cancer is not yet supported by any of the members of the ICGC.


Patent
University of Paris Descartes, French National Center for Scientific Research, French Institute of Health, Medical Research, Laboratoire Mabio International and University Paris - Sud | Date: 2015-12-16

The invention related to a device for cultivating cells comprising:- a lower part comprising at least two lower compartments, a lower wall separating the two lower compartments, and a semi-porous membrane covering the lower compartments, the semi-porous membrane comprising an upper surface intended to receive the cells;- a first upper part and a second upper part intended to be fitted onto the lower part, in order to obtain selectively:- a first configuration of the device wherein the first upper part is fitted onto the lower part, the first upper part forming an upper compartment wherein a culture medium can flow, in order to apply shear stress to the cells;- a second configuration of the device wherein the second upper part is fitted onto the lower part, the second upper part comprising at least two upper compartments, a wall separating the two upper compartments, and injection openings for injecting a substance to be tested in each upper compartment, the wall of the second upper part facing the wall of the lower element and being in contact with the semi-porous membrane so as to prevent a leakage of the injected substance from an upper compartment to another.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH-2009-1.4-2 | Award Amount: 15.47M | Year: 2010

Bone is among the most frequently transplanted tissue with about 1 million procedures annually in Europe. The worldwide market of bone replacement materials is currently estimated at 5 billion with a 10% annual growth. Despite their considerable disadvantages, including the risk of disease transfer and immunologic rejection, limited supply of bone, costs and complications, allografts and autografts account for more than 80% of total graft volume. Significant growth opportunities exist for synthetic bone grafts in association with mesenchymal stem cells from autologous or allogenic sources as alternatives to biological bone grafts in orthopaedic and maxillofacial surgery. The objectives of REBORNE is to perform clinical trials using advanced biomaterials and cells triggering bone healing in patients. In order to reach this goal, five phase II clinical studies with 20 patients are proposed in 12 clinical centres spread in 8 European countries. Three orthopaedic trials concerning the treatment of long bone fractures and osteonecrosis of the femoral head in adults or children will be conducted using bioceramics, hydrogel for percuteneous injection and stem cells from autologous or allogenic sources. Clinical research will also concern maxillofacial surgery with bone augmentation prior to dental implants and the reconstruction of cleft palates in children. The safety and efficacy of the new therapies will be assessed clinically using X-rays, CT scans and MRI as well as histology of biopsies. These ambitious clinical targets will require research and development efforts from a large consortium of top world class laboratories, SMEs manufacturing biomaterials, GMP-cell producing facilities and surgeons in hospitals as well as the consideration of ethical and regulatory issues. It is expected that REBORNE will expand the competitiveness of Europe through the patenting of new CE-marked bioproducts in the field of regenerative medicine.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH-2009-1.4-3 | Award Amount: 16.34M | Year: 2010

We propose to develop new strategies to mobilize skeletal muscle tissue-associated stem cells as a tool for efficient tissue repair. This will be combined with exploring novel approaches that limit tissue damage, and will focus on agents that modify muscle and muscle vasculature progenitor cells. These molecules include nitric oxide associated with non-steroidal anti-inflammatory drugs, HMGB1, Cripto, NAC, and present and improved deacetylase inhibitors. Three clinical trials will be run in tandem with efforts to dissect the underlying mechanisms of action. Importantly, we have already initiated a monocentric clinical trial that focuses on the efficacy of NO-donors plus NSAIDs in muscle pathologies. Our efforts will be complemented by novel biodelivery systems for effective targeting. Our efforts will be complemented by novel biodelivery systems for effective targeting. The most promising drugs, used alone or in combination, will be first validated in small and large animal models. Our project brings together leading investigators to examine how vascular and muscle progenitors participate in postnatal growth and muscle tissue repair. A key issue that this project addresses is the tissue environment in which endogenous stem cells are activated. We propose that muscle degeneration and fibrosis provokes altered vascularization and immune responses, which eventually affect negatively stem cell functions. Molecules that can be used to therapeutically target these key cells, and their communication with neighboring vascular, inflammatory and fibrotic cell types, will lead to more effective approaches to muscle regenerative medicine and to novel cures for degenerative diseases, including atherosclerosis, vascular damage in diabetes and in peripheral ischemic vascular disease.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2010.2.4.5-2 | Award Amount: 7.86M | Year: 2010

Chronic inflammatory diseases associated with allergy, including asthma and rhinitis, constitute a major and continuously growing public health concern for Europe. However, the causative factors and mechanisms converting a physiological inflammatory reaction to a chronic response triggering allergic disease remain elusive. Viral infections, particularly those caused by human rhinoviruses (RV) are the most frequent triggers of acute asthma exacerbations. RV infections have more recently been associated with asthma initiation; there is evidence suggesting that such infections may also contribute to respiratory allergy persistence. The strategic aims of PreDicta are to evaluate the hypothesis that repeated infections reprogram the immune system towards a persistent inflammatory pattern leading to respiratory allergies by (i) dissecting the molecular and cellular mechanisms involved in the lack of resolution of inflammation in the context of a human disease, (ii) identifying specific infectious agents and underlying altered host-pathogen interactions, and develop relevant prognostic and therapeutic strategies. PreDicta follows three interconnected workflows: models, mechanisms and translational output. Models include a longitudinal cohort in children, mouse models of repeated virus infection, primary epithelial cultures from patients, viral-bacterial interaction models, and models of epithelial-T-cell-dendritic cell interactions. These will be used to look into disease persistence, inflammation patterns, dysbiosis, immune regulation and resolution of inflammation. Translational outputs include prognostic use of subtype-specific antiviral antibodies, DNAZymes for therapeutic use and delivery technologies targeted to the bronchial epithelium. This interdisciplinary Consortium with strong track record, unique resources and strong translational focus, aims to produce new knowledge and technologies that can rapidly and effectively reach clinical care.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2011.2.4.3-2 | Award Amount: 9.96M | Year: 2011

The DIABAT project will employ knowledge of the function, dysfunction and physiological regulation of brown adipocytes to develop innovative therapeutic and preventive strategies for type 2 diabetes. Brown adipose tissue (BAT) is currently a worldwide recognized target to combat obesity and diabetes due to last years re-discovery of functional BAT in adult humans by several of the members of the DIABAT network (van Marken LIchtenbelt et al., N. Engl. J. Med. 360, 1500, 2009; Virtanen, Enerbck & Nuutila, N. Engl. J. Med. 360, 1518, 2009) along with sharp rise in insight in cellular, genetic, and regulatory mechanisms from animal studies. Therefore, the DIABAT project aims at recruiting and re-activating endogenous energy-dissipating BAT as a preventive and/or remedial measure for weight and blood sugar control in obesity-related type 2 diabetes (diabesity), thereby halting or preventing destruction and facilitating recovery of pancreatic beta-cells under diabetic conditions.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH-2009-1.4-1 | Award Amount: 16.14M | Year: 2010

There are currently no cures for Parkinsons disease (PD) but one of the most effective reparative therapies in patients to date has been with allotransplants of dopamine (DA) neuroblasts obtained from fetal ventral mesencephalic (VM) tissue. However, this cell transplantation approach has given inconsistent results, with some patients doing extremely well and coming off anti-PD medication for years, whilst others have shown no or only modest clinical improvements, and in some cases also developed severe, off-state graft-induced dyskinesias (GIDs). The reasons behind this heterogeneity of outcomes, and the emergence of GIDs in particular, need to be better understood, not least in the perspective of the rapid advances that are now being made in the development of stem-cell based therapies. There is therefore an urgent need to revisit the trials that have already been done with fetal VM tissue in PD patients, with the expectation that a critical reassessment can form the basis for an optimised and more standardised procedure that will translate into more consistently efficacious transplants with minimal side-effects. Over the last two years a group of international experts, including the key investigators of the previous European and North American trials, has been re-examining the outcome of these trials as well as reviewing the results obtained from recent and ongoing animal experimental studies, and identified a number of weaknesses that may explain the inconsistent outcome in previous trials. As a result of these discussions, the group has agreed to join forces in a new round of experimental work and cell therapy trials in PD, based on a new jointly developed protocol where all these factors are taken into account. In the first instance fetal VM tissue containing mesencephalic DA neuroblasts will be used, with the expectation that this will pave the way for bigger trials using dopaminergic neurons derived from stem cells.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: NMP.2011.1.4-4 | Award Amount: 5.16M | Year: 2012

NeuroCare aims to create better retinal, cortical and cochlear implantable devices through the use of improved interfacing between the electronic implants and living cells. The NeuroCare concept involves low-cost, carbon-based materials, well-adapted for medical implants, because they (i) offer wide range of electronic properties (metal, semiconductor and insulator), (ii) are bio-inert and (iii) are physically robust. Coupling between electronic devices and neurons was recently studied using soft, nanocrystalline diamond-based micro-electrode arrays, evaluated in laboratory animals for retinal stimulation. These diamond implants considerably reduced gliosis, enabled stimulation currents to be raised by more than one order of magnitude before causing visible chemical alteration, and enabled long lasting operation with reduced biofouling. Our previous experience with nanocrystalline diamond will be directly built upon through the introduction of atomic layers of graphene to diamond surfaces. NeuroCare will specifically focus on: Carbon-biointerface development offering reduced biofouling over the state-of-the-art, as set by the DREAMS project and improved biocompatibility Interfacing of rigid MEAs and FETs with cells and organs to improve bidirectional communication with neurons for in vitro research and pharmacological applications Nanoscale surface engineering and flexible macroscale implant materials for optimal contact to biological tissue Making and testing implantable MEAs and FETs for complex multichannel neuronal communication - targeting the specificity in vivo of the implantable devices for 3 high-impact clinical applications Neurocare partners will test interfaceable and implantable devices via in vitro and in vivo testing. NeuroCare federates 12 partners: CEA (LIST and CLINATEC), Ecole Suprieure dIngnieurs en Electronique, Forschungszentrum Jlich, Ayanda Biosystems SA, University College London (London Centre for Nanotechnology), Johannes


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.2.2.1-2 | Award Amount: 7.78M | Year: 2013

Our proposal is based on the idea that real-time functional neuroimaging can be used to train patients to regulate their own brain activity via neurofeedback training and thus modulate the brain networks of mental disorder, restore function, improve symptoms and promote resilience. We have brought together the core groups that have been instrumental in the development of methods for real-time functional imaging and fMRI (functional magnetic resonance)-based neurofeedback and have led the initial clinical applications in neuropsychiatric disorders. Our proposal has three main components, the development and refinement of methods for the real-time analysis and feedback of fMRI data and combination with other imaging modalities (WP2), the adaptation of fMRI mapping techniques to localise disease-relevant networks and development of protocols for their self-regulation through neurofeedback (WP3) and the assessment of feasibility and clinical effects in several mental disorders that are characterised by dysfunctional brain systems for motivation, emotion regulation and social communication and by important therapeutic gaps (autism spectrum disorders, alcohol addiction, post-traumatic stress disorder, childhood anxiety disorders, binge-eating disorder) (WP4). We will also explore the potential transfer of (laboratory-based) imaging feedback training into everyday settings through ambulatory and assistive technologies such as electroencephalography (EEG) and gaming (WP5). We will engage with potential users of these technologies (healthcare professionals and providers, medical instrument and software manufacturers, patient and carer associations) through several workshops, liaise with regulatory authorities and disseminate findings to the academic and user communities in WP6.


Grant
Agency: Cordis | Branch: FP7 | Program: CSA-CA | Phase: HEALTH.2012.4.1-4 | Award Amount: 970.62K | Year: 2012

The ECRAN (European Communication on Research Awareness Needs) project is designed to develop a portfolio of open educational resources, including a film, for the general population about the challenges raised by independent clinical research. The European Commission (FP7 Health Priority) decided to allocate substantial funding to independent (investigator-driven) clinical trials. Together with member states, the FP7 infrastructure unit supports the preparation and operation of a pan-European infrastructure for clinical trials (ECRIN). Through these instruments, Europe has the capacity to design and conduct independent, multinational clinical trials. The objective of the ECRAN project is to develop tools to communicate key messages to citizens, patients, healthcare professionals, researchers, policymakers and society about independent, multinational clinical research. These messages will focus on: i) the importance of public understanding of the need for and basic principles of clinical trials, fostering active involvement of patients in trials and of their representatives in trial design; ii) the need for independent clinical trials driven by healthcare issues, to optimise treatment strategies through comparison of benefits and harms of multiple therapeutic options, supporting evidence-based clinical practice and reduction in healthcare inequalities; iii) the need for transparency and optimal use of data, to promote the cost-effectiveness of treatments and to reduce the economic burden of diseases; iv) the need for multinational cooperation, taking advantage of Europes population size and diversity, and of its medical expertise. These objectives will be addressed using communication tools, including: a website, with an online database of open educational resources in different European languages; a film on clinical trials, dubbed in many languages, which is envisaged as a keystone of this initiative; an international event on multinational clinical trials.


Grant
Agency: Cordis | Branch: FP7 | Program: MC-IAPP | Phase: FP7-PEOPLE-2011-IAPP | Award Amount: 1.60M | Year: 2012

BRAINVECTORS aims devising new gene therapy(GT)-based treatments for Parkinsons and other neurodegenerative diseases, in substitution of current systemic treatments, by delivering neurotrophic factors (GDNF) into the CNS with new vectors derived from adeno-associated (AAV), canine adenoviruses (CAV) and lentiviruses (LV) with inducible gene expression. Although AAV, CAV and LVV are considered acceptable in terms of bio-safety, their immune response must be well characterized in order to further develop these vectors for clinical trials. Furthermore, the possibility to switch-off the expression of neurotrophic factors in case of adverse effects represents a significant pharmacological progress of the gene therapy approach for Parkinsons disease. BRAINVECTORS will: - devise new inducible gene expression cassettes with increased sensitivity of transactivators and inducers reducing thus the dose of drugs necessary to obtain GDNF expression in brain; - characterise the immune responses induced by the components of GDNF-AAV, -CAV and -LVV in rodent models for Parkinsons disease by using biomarker-based immunological screening. The project is based upon a network of 12 participants of public academic institutions and private non-profit organisations and SMEs in France, Germany, Italy, Netherland, Portugal, Spain, Sweden and Switzerland. Some of them are traditionally linked together in developing vectors backbones, vector production technologies and Parkinsons animal models. Others have strong immunological background, pioneering the biomarkers-based immuno-technologies for GT vectors, and have R&D expertise/facilities on/for animal cell technologies cGMP for biopharmaceuticals. 142 p-m will be involved during 48 months in R&D and TOK activities with 72 p-m of recruited postdocs and 70 p-m of seconded staff.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.2.4.2-1 | Award Amount: 8.18M | Year: 2013

The Fibro-Targets project is a multi-disciplinary 4 years program involving 10 partners ambitioning the identification, characterisation and validation of in vitro and in vivo models of novel therapeutically relevant targets for myocardial interstitial fibrosis (MIF) in heart failure. The project is based on the hypothesis that the intervention on novel fibrosis-related targets involved in the processes of fibroblast differentiation to myofibroblasts, the predominance of collagen synthesis over degradation and/or collagen maturation may allow for interstitial repair, thus providing a new strategy for the prevention and treatment of adverse cardiac remodeling involved in the transition to and the progression of heart failure. From a large body of existing multi-omics, literature data and previous hypothesis-driven research conducted by members of the consortium, a number of specific extracellular and intracellular targets have been identified whose involvement in MIF is beginning to be understood and that may be targeted by specific therapies. The specific aims of the Fibro-Targets are: (i) To provide further evidence on the mechanisms of action of the above targets (ii) To validate experimentally that new anti-fibrotic strategies can be developed based on the above targets (iii) To approach the potential clinical scenario of the above targets for HF therapy To reach these aims the following studies will be performed: (i) Observational and interventional experimental studies in already existing and/or de novo generated appropriate in vitro and in vivo models. (ii) Clinical studies, stratifying large scale populations of patients available to the consortium, at risk to develop HF and likely to be responsive to specific novel and/or exiting anti-fibrotic therapies. The stratification will be based on specific fibrogenetic phenotypic profiles using multi-panel imaging and circulating markers descriptive of mechanisms involving the proposed novel targets.


Grant
Agency: Cordis | Branch: FP7 | Program: CSA-CA | Phase: HEALTH.2012.4.1-4 | Award Amount: 1.09M | Year: 2012

The strategic objective of HIGHLIGHT is to contribute to the development of public awareness on European Health research in all European countries through the professional use of television media and the internet. The technical objectives of HIGHLIGHT are: Surf the Health Theme in FP7 to identify most prominent results achieved by individual projects in FP7. Produce and release a series of 21 high-quality free-of-rights short TV reportages for the general public on the basis of the key results of the research. Projects audiovisuals will be developed in such a way to be easily adaptable to the needs of a wide spectrum of European TV channels and languages. Exploit the distribution potential of the Consortium and deliver the TV reportages to 200\ TV programs in Europe, to the news and to the main European broadcasting gateways, targeting all principal TV broadcast media from the 27 EU Member States and beyond. Produce and release a series of original articles around the TV reportages written by professional journalists for the press and on-line media on the basis of the key results of the research. Translate the released TV reportages in 6 languages and engrave them onto a DVD for public use at conferences, fairs, workshops, etc. The layout of the DVD shall be in line with DG R&I audiovisual communication policy. Monitor the progress of the project and quantify the overall media impact of the project. On the basis of the above, HIGHLIGHT expects: To have each of its audiovisual productions took-up and/or broadcast by national European TV stations at least 10 times, for a minimum expected total of 210 take-ups/broadcasts made by public TV stations in Europe and beyond, for a total of several millions viewers. To have each of its web articles seen, took-up and mirrored at least 35 times, for a minimum expected total of 2,205 referrals on on-line news, specialised magazines, blogs, fora, social networks, etc.


So far, there are no effective treatments for neuropathic pain (NP), and current treatments suffer from serious unwanted side effects. The NGF ligand-receptor system has recently emerged as a novel target for NP of great therapeutic potential, a master regulator, controlling both neuropathic and inflammatory components. Besides being a multi-component system, it also modulates the endocannabinoid (EC) signalling. Blocking the NGF signaling system is therefore a rational and thoroughly validated approach to pain therapy. Extensive evidence for potent analgesic efficacy of antiNGF mAbs has been obtained in preclinical models and in clinical trials,showing remarkable analgesic efficacy and creating great expectations for this new class of analgesic compounds.However, potential safety concerns related to off-target side effects have been raised and recently the FDA called for more preclinical research. To fully exploit the huge therapeutic potential of NGF system, we built a consortium of leading researchers in the NGF, EC and pain scientific arena.The innovative proposal will investigate new strategies for the treatment of different NP forms, based on the NGF system and its interplay with EC signalling, focussing at different levels of the pain transmission and perception systems. The project results will provide solid, mechanism-based grounds for the development of already identified second-generation therapeutics, based on the NGF target system, as well as for the identification and validation of new druggable targets emerging from the elucidated mechanisms. It will also identify biomarkers for NP, validated in animal models and clinical samples, that could result in future clinical benefits, for the stratification of patients suffering from different neuropathies and their treatment. The project will contribute to the understanding and controlling NP mechanisms, with an interdisciplinary approach, leading to the development of next-generation NGF targeting drugs.


Grant
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: PHC-01-2014 | Award Amount: 7.26M | Year: 2015

The dramatic differentials in healthy ageing, quality of life and life expectancy between individuals of different socioeconomic groups, is a major societal challenge facing Europe. The overarching aim of the LIFEPATH project is to understand the determinants of diverging ageing pathways among individuals belonging to different socio-economic groups. This will be achieved via an original study design that integrates social science approaches with biology (including molecular epidemiology), using existing population cohorts and omics measurements (particularly epigenomics). The specific objectives of the project are: (a) To show that healthy ageing is an achievable goal for society, as it is already experienced by individuals of high socio-economic status (SES); (b) To improve the understanding of the mechanisms through which healthy ageing pathways diverge by SES, by investigating lifecourse biological pathways using omic technologies; (c) To examine the consequences of the current economic recession on health and the biology of ageing (and the consequent increase in social inequalities); (d) To provide updated, relevant and innovative evidence for healthy ageing policies (particularly health in all policies) that address social disparities in ageing and the social determinants of health, using both observational studies as well as an experimental approach based on the existing conditional cash transfer experiment in New York. To achieve these objectives we will use data from three categories of studies: 1. Europe-wide or national surveys combined with population registry data; 2. Cohorts with intense phenotyping and repeat biological samples (total population >33,000); 3. Large cohorts with biological samples (total population >202,000). The cohorts will provide information on healthy ageing at different stages of life, based on the concepts of life-course epidemiology (build-up and decline) and multimorbidity.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: NMP-2009-4.0-3 | Award Amount: 16.52M | Year: 2010

NAMDIATREAM will develop a cutting edge nanotechnology-based toolkit for multi-modal detection of biomarkers of most common cancer types and cancer metastases, permitting identification of cells indicative of early disease onset in a high-specificity and throughput format in clinical, laboratory and point-of-care devices. The project is built on the innovative concepts of super-sensitive and highly specific lab-on-a-bead, lab-on-a-chip and lab-on-a-wire nano-devices utilizing photoluminescent, plasmonic, magnetic and non-linear optical properties of nanomaterials. This offers groundbreaking advantages over present technologies in terms of stability, sensitivity, time of analysis, probe multiplexing, assay miniaturisation and reproducibility. The ETP in Nanomedicine documents point out that nanotechnology has yet to deliver practical solutions for the patients and clinicians in their struggle against common, socially and economically important diseases such as cancer. Over 3.2M new cases and 1.7M cancer-related deaths are registered in Europe every year, largely because diagnostic methods have an insufficient level of sensitivity, limiting their potential for early disease identification. We will deliver Photoluminescent nanoparticle-based reagents and diagnostic chips for high throughput early diagnosis of cancer and treatment efficiency assessment Nanocrystals enabling plasmon-optical and nonlinear optical monitoring of molecular receptors within body fluids or on the surface of cancer cell Multi-Parameter screening of cancer biomarkers in diagnostic material implementing segmented magnetic nanowires Validation of nano-tools for early diagnosis and highly improved specificity in cancer research. OECD-compliant nanomaterials with improved stability, signal strength and biocompatibility Direct lead users of the results will be the diagnostic and medical imaging device companies involved in the consortium, clinical and academic partners


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2010.2.3.2-1 | Award Amount: 16.70M | Year: 2011

The More Medicines for Tuberculosis (MM4TB) consortium evolved from the highly successful FP6 project, New Medicines for TB (NM4TB), that delivered a candidate drug for clinical development two years ahead of schedule. Building on these firm foundations and exploiting its proprietary pharmacophores, MM4TB will continue to develop new drugs for TB treatment. An integrated approach will be implemented by a multidisciplinary team that combines some of Europes leading academic TB researchers with two major pharmaceutical companies and four SMEs, all strongly committed to the discovery of anti-infective agents. MM4TB will use a tripartite screening strategy to discover new hits in libraries of natural products and synthetic compounds, while concentrating on both classical and innovative targets that have been pharmacologically validated. Whole cell screens will be conducted against Mycobacterium tuberculosis using in vitro and ex vivo models for active growth, latency and intracellular infection. Hits that are positive in two or more of these models will then be used for target identification using functional genomics technologies including whole genome sequencing and genetic complementation of resistant mutants, yeast three hybrid, click chemistry and proteomics. Targets thus selected will enter assay development, structure determination, fragment-based and rational drug design programs; functionally related targets will be found using metabolic pathway reconstruction. Innovative techniques, based on microfluidics and array platforms, will be used for hit ranking, determining rates of cidality and confirming mechanism of action. Medicinal chemistry will convert leads to molecules with drug-like properties for evaluation of efficacy in different animal models and late preclinical testing.


RDEB is one of the most severe rare genetic skin diseases of children and adults characterized by skin blistering resulting from lack of expression of type VII collagen. There is no treatment for this life-threatening disease. In March 2009, we obtained the orphan drug designation for the Medicinal product: Skin equivalent graft genetically corrected with a COL7A1-encoding SIN retroviral vector, which was developed during the THERAPEUSKIN project (FP6) to treat RDEB patients by ex vivo gene therapy. This approach uses autologous skin grafts made of primary keratinocytes and fibroblasts genetically corrected with a safe (SIN) retroviral vector expressing type VII collagen under the control of the EF1alpha promoter. We have demonstrated the feasibility of the approach in pre-clinical studies in mice and the absence of tumorigenicity. We now aim at preparing and undertaking a first clinical trial in 3 selected RDEB patients. This project will involve the transfer and the adaptation from the research laboratory to clinic, of the entire experimental procedure for genetic correction of RDEB skin equivalents suitable for transplantation in patients. This will include validation of the viral pilot batches and the GMP viral vector lot, the establishment of SOPs, the identification and selection of the best GMP culture system and the scale-up of the graft preparation. A clinical-grade cell bank of primary keratinocytes and fibroblasts will be established from 3 selected RDEB patients who are tolerant towards type VII collagen. Determination of transgene integrity, analysis of the proliferative capacities of transduced keratinocytes and the level of type VII collagen expression will be assessed. Safety assessment will include tumorigenicity assays, survey of grafted genetically corrected skin and integration site analysis. The regulatory and safety issues of these procedures related to the preparation of clinical grade genetically modified cells suitable for human transplantation will be addressed. Authorization of the clinical trial by the AFSSAPS will allow the first patients to be treated and followed up. This bench to bedside project will serve as a proof of principle of safe gene therapy for RDEB. It has the potential to bring clinical improvement to these young patients and to represent a significant progress in the treatment of this devastating skin disease.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.1.3-3 | Award Amount: 8.14M | Year: 2013

Cardiovascular disease (CVD) is still a leading cause of death in the European Union (EU) accounting for nearly half of all deaths in Europe (48%). In addition, CVD complications lead to a vast number of hospitalizations and thus to a great burden of health care costs in the EU. Atherosclerosis and its final complication, plaque rupture and subsequent infarct in heart or brain, is the main underlying pathology of CVD and atherosclerosis is responsible for 70% of all cases of CVD. Extensive studies into the pathology of atherosclerosis show that its etiology is found in a combination of dyslipidemia and a related inflammatory response with an established autoimmune component, while the major cause of acute CVD events, plaque rupture, due to an inflammatory destabilization of the atherosclerotic lesion. CVD is therefore an autoimmune-like disease in the context of a metabolic disease. Thus far, therapeutic approaches in CVD have been focused at normalizing dyslipidemia in order to lower plasma cholesterol. Statins and additional surgical approaches such as angioplasty have achieved a 30% risk reduction for CVD during the last 10-15 years. However, additional approaches to improve the treatment of dyslipidemia by for instance improving the level of the anti-atherogenic lipoprotein HDL have failed in a number of clinical trials. This implicates that new therapeutic approaches are urgently needed to narrow down the remaining 70% risk for CVD. We aim to develop a new immunomodulatory treatment, a therapeutic vaccine that permanently restores the immune balance within the arterial wall by inhibiting the inflammatory responses during atherosclerosis. The VIA consortium aims to develop a vaccine, dissect the immune pathways underlying the beneficial effect of the vaccine, optimize the vaccine, test its safety and perform a phase I clinical trial using the atheroprotective vaccine. The vaccine is foreseen to result in a substantial lowering of the risk for CVD.


Grant
Agency: Cordis | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2014-ETN | Award Amount: 3.11M | Year: 2015

Drug development is a long and costly process which suffers from the major shortcoming that frequently failure is often only determined during the final stage. Recently, it has been recognised that more care needs to be taken during the early stages of development to avoid going into lengthy and costly confirmatory studies with ineffective or harmful treatments. To achieve this goal it is essential to implement efficient methods for the design and analysis of such early development studies. The expertise in this area is, however, limited at the moment and adequate methodology is only partially available. Using a cross-sectorial, transnational approach, the IDEAS network brings together leading public and private sector researchers in the field with ample experience in training to educate, promote and support the future leaders in medical statistics in general and in the design and analysis of early developmental studies in particular. Within the network, cross-sectorial, transnational teams will support young researchers with individual methodological projects and devise an individually tailored training programme for them. Clinical advisors supplement the input of the supervisory team and ensure practical relevance and uptake of the methods devised. The training activities are comprised of a well-rounded mix of specialist, methodological components and generic, transferable skills. A mandatory set of networkwide training activities is supplemented by individual training components and cross-sectorial secondments, and particular attention is given to interaction and collaboration between researchers and supervisors across public and private sector partners. At the end of their training the researchers will be uniquely qualified with expertise in the field, benefit from experience in both public and private sector and can rely on a wide network of experts in the field in the future.


Amyotrophic Lateral Sclerosis (ALS) is a fatal degenerative disorder of the brain and spinal cord affecting some 40,000 individuals in Europe, causing 11,000 deaths each year. Our pioneering work on riluzole showed that it is possible to modify ALS progression but all subsequent trials of potential neuroprotective agents have failed. Thus, drug development in ALS, including trial design, patient selection, and outcome measures must be re-engineered to break the current impasse. Nerve cell death in ALS is associated with inflammation, which contributes to cell damage, and is a logical target for therapy. Although therapeutic attempts to modify this have failed so far, the discovery of regulatory T cells (Tregs) as key players in controlling inflammatory processes opens new possibilities since defective Treg function is important in ALS. In fact, Treg numbers and function predict rates of disease progression and survival. Low-dose interleukin-2 (ld IL-2) safely and specifically increases and activates Tregs in conditions such as type 1 diabetes, HBc-vasculitis and chronic graft-versus-host disease, so ld IL-2 has the potential to significantly improve survival and deliver a therapeutic breakthrough in ALS. We also integrate biomarkers for nerve cell damage into the trial design to provide proof of concept/mechanism. Modifying Immune Response and OutComes in ALS (MIROCALS) will test the hypothesis that ld IL-2-induced increases in Tregs result in decreased rates of nerve cell damage and that this effect can be detected early in the course of the disease using a range of blood and cerebrospinal fluid biomarkers. Our ambition is to develop a new therapy for ALS and through this novel trial design break the impasse in drug development of other disease-modifying agents in ALS. The impact will be to enhance quality of life and care for people with ALS, and provide a robust model for Industry to encourage investment in ALS and other neurodegenerative diseases.


Grant
Agency: Cordis | Branch: FP7 | Program: CSA-CA | Phase: HEALTH.2011.2.2.1-5 | Award Amount: 2.21M | Year: 2012

Research into the human brain and its diseases is one of the key challenges of our century, since among the many diseases affecting health, disorders of the brain are major causes for impaired quality of life. Despite some progress in understanding the molecular mechanisms of the various neurological and psychiatric disorders, research is far from being able to offer solutions how to conquer them and the development of curative treatments or prevention strategies has not been very successful. Thus, a concerted effort of research groups and the organisations funding them is needed to reach the long term goal of curing patients with disorders of the brain and nervous system and helping their relatives. Due to the importance of research into the area of brain diseases, a variety of independent national and regional funding programmes exist in most countries. This contributes to fragmentation of available financial resources, to a lack of synergistic approaches and to duplication of efforts in the funding bodies. The proposed ERA-NET NEURON II aims to coordinate national and regional programmes for disease-related neuroscience research in 21 participant funding organisations across 16 European Member States, Candidate and Associated countries, and Canada. Extending the collaboration beyond the European Research Area into North America reflects the global dimension of brain research and adds even more to the effectiveness of NEURON. The ERA-NET will serve as a platform of programme opening for participating funding agencies and ministries and coordinate high quality research by funding research groups originating from the NEURON II partner countries. NEURON II will build on the achievements of its predecessor ERA-NET NEURON. It will launch a series of transnational joint calls for proposals and address new ambitious goals by developing strategies towards a self-sustainable network with a long term perspective.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2010.2.4.2-2 | Award Amount: 8.19M | Year: 2011

Current interventional treatment of acute myocardial infarction (AMI) focused on re-establishing cardiac reperfusion has significantly improved clinical outcome by reducing infarct size and mortality due to cardiac ischemia.It is now recognized that events triggered at reperfusion also result in cell death and may account for as much as 50% of the infarct volume, this being termed ischemia-reperfusion injury (IRI). Mitochondrial permeability transition pore (mPTP) opening appears to be a responsible for IRI and a recent small clinical trial with cyclosporine A shows that it is a feasible target for the development of new therapies to treat it. Since total infarct size is a major determinant of a patients risk to develop heart failure, treating IRI is expected to further reduce morbidity, mortality and the need for regenerative medicine following cardiac ischemia. By harnessing a multi-disciplinary consortium of clinical and basic scientists along with four SMEs, MitoCare brings state-of-the art expertise together to 1) better understand IRI pathophysiology and factors directly or indirectly influencing patients recovery or response to treatment; 2) investigate the translational usefulness of preclinical models; and 3) compare selected treatments. These objectives will be reached through the following work plan: A) a medium-scale phase II clinical study will evaluate the efficacy of a novel complementary therapy to PCI, the new mPTP modulator TRO40303, while at the same time 1) perform extensive sampling from subjects in the study for analysis of standard and emerging biomarkers; 2) identify confounding factors influencing patients outcomes. B) Parallel investigations in preclinical in vitro and in vivo AMI models. C) Statistical analysis of data from clinical and preclinical studies, to identify better diagnostic and prognostic endpoints in man and assess predictive utility of preclinical models.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP-SICA | Phase: HEALTH.2010.2.4.1-4 | Award Amount: 4.78M | Year: 2011

Chronic hepatitis B virus (HBV) infection affects 350 million people worldwide and 25-30% of these individuals will die as a result of their infection mainly as a results of hepatocellular carcinoma HCC. Liver cirrhosis, high viral load and dietary exposure to aflatoxin are recognised as risk factors for hepatocellular carcinoma amongst HBV carriers. However, these variables do not account for all cases of HCC and decompensated cirrhosis is rarely ever seen in West Africa suggesting that advanced liver fibrosis may not be an important risk factor in this population. A large case control study on HCC will be used to evaluate the importance of liver fibrosis and other established risk factors in West Africa and to explore other potential oncogenic determinants. The case-control study will generate serum, urine and DNA samples for proteomic, metabonomic and genomic analysis to identify biomarkers and aetiological agents for HCC. Effective treatment for HBV infection is now available in the developed world but treatment programmes have not been developed for resource poor settings even though some of the effective medication is now available at low cost for HIV management. A trial of HBV treatment in a group of carefully selected high risk patients will be conducted to demonstrate that the incidence of HCC can be reduced in this population as has been observed in Asian patients. The treatment trial will also be used to evaluate the efficacy of screening by ultrasound for early tumours which can be treated with percutaneous alcohol injection. This comprehensive programme therefore aims to reveal novel aetiological factors for HCC, identify and evaluate biomarkers and demonstrate the efficacy of selective antiviral therapy to prevent HCC


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.2.3.4-2 | Award Amount: 8.64M | Year: 2014

This proposal builds on the proven methodology developed in the SEtTReND FP7 project to develop inhibitors of schistosome HME as lead compounds for new drugs. We will employ a target-based strategy for the development of novel drug leads against schistosomiasis, leishmaniasis, Chagas disease and malaria by targeting histone modifying enzymes (HME), in particular those involved in acetylation/deacetylation and methylation/demethylation. The principal objectives of A-PARADDISE are: - The identification of HMEs from Leishmania sp. and Trypanosoma cruzi and the molecular characterization and functional characterization of selected potential targets, - Phenotypic screening of Leishmania, T. cruzi, S. mansoni and P. falciparum using HME class inhibitors, inhibitors developed specifically against S. mansoni and P. falciparum HMEs. This will permit us to obtain a comprehensive view of inhibitor classes and chemical scaffolds of interest, - Production of recombinant Leishmania and T. cruzi HME proteins, structural studies. Selected, validated target enzymes will be produced, crystallized and analysed by X-ray diffraction. Assays will be optimized to permit testing of inhibitors, - High-throughput and structure-based (in silico) screening of selected HMEs. Inhibitors selected will be further screened by phenotypic assays on the parasites in vitro, - Optimisation of inhibitor structures by chemical synthesis based on molecular modelling studies (inhibitors of all origins), - Transcriptomic analysis of drug-treated parasites to verify target specificity and mechanism of action (all parasites), - Pharmacological and toxicological studies (in vitro and in vivo) of selected inhibitors, in vivo testing of compounds in parasite-infected mice. The overall objective of the A-PARADDISE project is to develop optimized epigenetic inhibitors for further testing and optimisation as drug candidates against the four parasites studied.


Grant
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: PHC-09-2015 | Award Amount: 24.09M | Year: 2015

HIV-1 is responsible for a global pandemic of 35 million people, and continues to spread at a rate of >2 million new infections/year. It is widely acknowledged that a protective vaccine would be the most effective means to reduce HIV-1 spread and ultimately eliminate the pandemic, while a therapeutic vaccine may help mitigate the clinical course of disease and lead to strategies of viral eradication. However despite 30 years of research, we do not have a vaccine capable of protecting from HIV-1 infection or impacting on disease progression. This in part represents the challenge of identifying immunogens and vaccine modalities with reduced risk of failure in late stage development. To overcome this bottleneck some of the most competitive research groups in vaccine discovery from European public institutions and biotechs from 9 EU countries together with top Australian and Canadian groups and US collaborators, have agreed to join forces in EAVI, providing a pool of international expertise at the highest level. EAVI2020 will provide a platform for the discovery and selection of several new, diverse and novel preventive and/or therapeutic vaccine candidates for HIV/AIDS. Emphasis will be placed on early rapid, iterative, small Experimental medicine (EM) human vaccine studies to select and refine the best immunogens, adjuvants, vectors, homologous and heterologous primeboost schedules, and determine the impact of host factors such as gender and genetics. Animal models will be used to complement human studies, and to select novel immunization technologies to be advanced to the clinic. To shift the risk curve in product development we will develop innovative risk prediction methods, specifically designed to reduce the risk associated with late stage preventive or therapeutic vaccine failure, increasing the chance of discovery of an effective vaccine.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH-2009-2.3.2-4 | Award Amount: 15.44M | Year: 2010

Despite significant effort over the past decade to design and implement new vaccines strategies against HIV, no one has met its promise to prevent infection and/or to reduce viral load until reaching eradication of the HIV reservoir. To reach this goal, a translational research is critical to propose innovative approaches for an HIV vaccine enhancing broadly cross-reactive mucosal, humoral and cellular immune responses specific to HIV antigens. Composed by 13 partners from 5 European countries and 2 International Cooperation countries, the CUTHIVAC consortium gathers knowledges and cutting-edge technologies in vaccinology and HIV diseases to raise the challenge of developing a new HIV strategy. The CUTHIVAC approach is based on innovative transcutaneous and/or mucosal needle-free vaccination methods in a perspective that new vaccine candidates will redirect immune response toward cytotoxic CD8 and mucosal humoral responses. The trust of the project derives from the proof-of-concept that combination of routes of immunization and delivery systems will shape the immune responses towards its protective arms against HIV. Clinical trials will be implemented with last cutting-edge generation of HIV DNA-GTU candidate applied by transcutaneous, intradermal routes and/or mucosal administration of HIV-envelop protein-based vaccine. Large efforts will be positioned on the new genetic design of HIV antigens and delivery systems for developed and developing countries. These new vaccines will be tested in innovative preclinical approaches with a special highlight on routes of vaccination that will be translated into 2nd round of clinical trials in a perspective that could help to prevent and eradicate HIV. Through its integrative and multidisciplinary approach, CUTHIVAC will therefore provide the basis for a novel approach in vaccination with a view to wide its application to other infectious diseases such as malaria and tuberculosis.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.1.3-2 | Award Amount: 7.79M | Year: 2014

Immune system response is the most complex barrier to long-term success of tissue transplants/implants from allogeneic and bio-artificial sources. While newly developed tissue transplant procedures are not yet performed frequently enough for robust analysis of adverse immune responses in humans, corneal transplantation (CT) is a well-established allogeneic tissue transplant with >100,000 full- and partial-thickness procedures performed annually. Adverse immune responses occur in up to 30% of CT recipients causing rejection and failure. The high levels of CT clinical activity and immune complications create an ideal opportunity to comprehensively profile immune responses associated with adverse tissue transplant outcomes and to develop new approaches for their prevention or early diagnosis. VISICORT is a multi-disciplinary project with expertise in basic immunology, bio-sampling, systems biology/immune profiling, bioinformatics, clinical tissue transplantation and cell therapy. It will complete the first systematic immune profiling of biological samples from animal and human CT recipients with diverse outcomes. Clinical data and bio-specimens from over 700 CT recipients at 5 leading transplant centres will be centrally collated and distributed to cutting-edge university- and SME-based laboratories for multi-platform profiling and integrated bioinformatics analyses. Profiling data will generate better understanding of adverse immune reactions to tissue transplants. This knowledge will be used to develop novel biomarker-based surveillance strategies and, coupled with SME-based expertise in cell product development, will also inform the design and initiation of an optimised clinical trial strategy of immunomodulatory stromal stem cell therapy in high-risk human CT recipients. VISICORT research will strongly impact multiple EU research/scientific communities, patient cohorts and SMEs and will have high commercialisation value for the biopharmaceutical and biotechnology industries.


Grant
Agency: Cordis | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2015-ETN | Award Amount: 3.65M | Year: 2015

Endoplasmic reticulum (ER) stress is emerging as a common feature in the pathology of numerous diseases including cancer, neurodegenerative disorders, metabolic syndromes and inflammatory diseases. Thus ER stress represents a potential therapeutic intervention point to be exploited to develop novel therapies, diagnostic tools and markers for these diseases. However, exploitation is hampered by the shortage of scientists with interdisciplinary training that can navigate with ease between the academic, industrial and clinical sectors, and that have the scientific and complementary skills, together with an innovative outlook, to convert research findings into commercial and clinical applications. This proposal will bring young researchers together with world-leading academics, clinicians and industry personnel, who are united in (1) their goal of forming a network of excellence aimed at understanding the ER stress response mechanistically and quantitatively and (2) applying this understanding to identify and validate the most suitable intervention points in order to provide innovative knowledge-driven strategies for the treatment of ER stress-associated diseases. The TRAIN-ERS network will provide early stage researchers (ESRs) with high quality scientific and complementary skills training combined with international, intersectoral work experience. This will produce highly trained, innovative, creative and entrepreneurial ESRs with greatly enhanced career prospects, who will continue to advance the state of the art in the Biomedical field in their further careers, and will confidently navigate at the interface of academic, clinical and private sector research. The TRAIN-ERS research programme will provide the ESRs with the knowledge and the cutting edge scientific and technical skills that will drive our understanding and exploitation of the ER stress response for therapeutic and diagnostic purposes.


Grant
Agency: Cordis | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2009-2.4.4-1 | Award Amount: 7.93M | Year: 2010

EFACTS (the European Friedreichs Ataxia Consortium for Translational Studies) assembles a body of expertise to adopt a translational research strategy for the rare autosomal recessive neurological disease, Friedreichs ataxia (FRDA). FRDA is a severely debilitating disease that leads to loss of the ability to walk and dependency for all activities. Some patients have cardiomyopathy that can cause premature death, visual and auditory loss, kyphoscoliosis, pes cavus, diabetes. Onset is usually in childhood, but it may vary from infancy to adulthood. FRDA involves child health and ageing aspects. FRDA affected individuals and clinical specialists are dispersed. This is a hindrance for patients to receive the care they need, and for clinicians and researchers to make progress. EFACTS has been created to move past this limitation. EFACTS strongly believes that, 12 years after European researchers discovered the FRDA gene, frataxin, when new treatments for FRDA are being developed, the time is ripe to invest in FRDA research in a concerted Europe-wide fashion. EFACTS gathers the critical mass of researchers and clinicians to exploit the patient base, research reagents and knowledge for progress. This comes when IT can act as a crucial support for collaborative work in collecting patient data and material, making it available to leading researchers for advanced analysis, research and drug development. This project proposal has the following scientific and technological objectives: 1. Comprehensively populate a European FRDA database, linked to a bio bank; 2. Define a panel of clinical assessment tools; 3. Build on the knowledge base of frataxin structure and function; 4. Build on the knowledge base of the pathogenic cascade; 5. Build on the knowledge base of epigenetic mechanisms of frataxin silencing; 6. Develop new cellular and animal models for the study of FRDA; 7. Identify FRDA biomarkers; 8. Identify genetic modifiers of FRDA; 9. Develop therapeutics for FRDA.


Grant
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: PHC-31-2014 | Award Amount: 2.65M | Year: 2015

FRESHER brings together ten research groups, including leaders in the management of large European Foresight projects and highly experienced health policy modelers, in an interdisciplinary team engaged in FoResight and Modelling for European Health policy and Regulation. The overall project objective is the representation of alternative futures where the detection of emerging health scenarios will be used to test future policies to effectively tackle the burden of non communicable diseases (NCDs). The project will produce quantitative estimates of the future global burden of NCDs in the EU and its impact on health care expenditures and delivery, population well-being, health and socio-economic inequalities, and potential changes in these impacts according to alternative health and non-health policy options. The added value of FRESHER lies in the fact that these estimates: - will not only be based on extrapolation of past health trends but also on foresight techniques (mapping of risk factors, horizon scanning and identification of key drivers for change, scenarios building) giving credit to the interdependencies of structural long-term trends in demography, gender relations, technological, economic, environmental, and societal factors at 2050. - will be produced through the development of an empirically-based micro-simulation model (starting from the Chronic Disease Policy Model of OECD), allowing to quantify the current and future health and economic impacts of NCDs and testing what if policy options according to alternative foresight scenarios, as well as potential new policies and policy combinations. FRESHER heavily relies on an interactive process with key stakeholders, at all stages of the project, in elaborating the framework, and giving inputs for the qualitative foresight scenarios and the quantitative micro-simulation model, and in deriving recommendations for future policies affecting population health and well-being.


Grant
Agency: Cordis | Branch: H2020 | Program: ERA-NET-Cofund | Phase: HCO-07-2014 | Award Amount: 30.95M | Year: 2015

Over 12 million people in Europe suffer from neurodegenerative diseases (ND), yet treatments that prevent or stop the progression of neurodegeneration are still lacking. Tackling this grand challenge requires enhanced coordination of national efforts to accelerate discovery. Such synergies have been created among 28 countries in the pilot EU JPI on Neurodegenerative Disease Research (JPND). JPND has a long standing experience in collaborative action with 75 million of additional national funds being successfully mobilized between 2011 and 2014 to support transnational research programs. The JPND Research Strategy is now ripe for further enhancement in tight coordination with the EC through an ERA-Net Cofund instrument JPco-fuND with an unprecedented commitment of 30 million of national funds associated to a highly incentivizing EC top-up fund. Among the most burning questions, three priority topics have emerged through a consultative process between researchers and JPND members in order to unlock several major issues within ND research: the identification of genetic, epigenetic and environmental risk and protective factors, the development and maintenance of longitudinal cohorts, the creation of advanced experimental models. These are key questions of equal priority to increase understanding of ND mechanisms that will be addressed through a common joint transnational call allowing a significant acceleration of the execution of the JPND research strategy. Moreover, to expand the impact of JPco-fuND, JPND will continue to implement other actions without EU co-funding such as aligning national research strategies, making databases more accessible and interoperable, developing enabling capacities such as supportive infrastructure and platforms, capacity building, education and training. These actions are required in parallel to achieve the highest impact for the patients, their carers and for society as whole and address this grand challenge in the coming years.


Grant
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: PHC-15-2015 | Award Amount: 6.34M | Year: 2015

Stroke is the second leading cause of death in the world population. When not fatal, stroke often results in disability, due to motor and cognitive impairments, and secondary health problems affecting not only patients but also their families. Building on emerging preclinical and pilot clinical evidences, RESSTORE will focus on the clinical assessment of regenerative cell therapy to improve stroke recovery and patients quality of life. RESSTORE European multicentre randomised phase IIb will explore, for the first time, the efficacy (functional recovery) and safety of intravenous infusion of allogenic adipose tissue derived mesenchymal stem cells (ADMSCs) in 400 stroke patients. Therapeutic effects of ADMSCs will be assessed and monitored in patients using clinical rating scales, multimodal MRI and novel blood biomarkers. Additionally, the societal value and cost-effectiveness of ADMSCs-based regenerative therapy will be evaluated through health economics and predictive in silico simulations. Complementary ancillary animal studies will support the clinical trial by defining i) if the treatment response can be further enhanced by intensive rehabilitation, ii) the contribution of co-morbidities and iii) the mechanism(s) underlying the therapeutic effect. The European regenerative therapy capacities (France, Spain, Finland, United Kingdom and Czech Republic), developed in RESSTORE will cover the full value chain in the field (large scale GMP cell production, clinical testing, biomarkers discovery, understanding of the restoring mechanisms, modelling, biobanking, economic studies, exploitation and communication plan). RESSTORE will thus surely contribute, together with the workforce trained in the context of the programme, to improve its public and private (SME) competitiveness and increase the attractiveness of Europe as a reference location to develop and clinically assess new innovative therapeutic options for brain diseases.


Grant
Agency: Cordis | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2014-ETN | Award Amount: 3.89M | Year: 2015

Cancer is a leading health concern. There is a need to fully understand the fundamental processes underlying development of cancer. There is increasing evidence that G protein-coupled receptors (GPCRs) and their associated signalling cascades are involved in both cancer progression and metastasis. As oncogenic GPCRs are likely to be amenable to manipulation via drugs they are ideal therapeutic targets. In ONCORNET (Oncogenic Receptor Network of Excellence and Training) we propose to target two oncogenic GPCRs; the chemokine receptors CXCR4 and CXCR7. These are highly expressed in a range of tumours and yet their role in cancer progression is not well understood. We will focus on unravelling how CXCR4 and CXCR7 are or can be modulated (small molecules, pepducins, nanodies) and investigate the effects on oncogenic responses. This represents crucial knowledge that we currently do not have and yet may well provide potential leads for drug development and commercialisation. ONCORNET will bring together the leading research scientists and labs in Europe with an interest in GPCRs and 15 early stage researchers. We will employ all the latest multidisciplinary research technologies to understand the role of these GPCRs in cancer and develop CXCR4 and CXCR7 tools for diagnostic and therapeutic purposes. Importantly, developed approaches can be extrapolated to other oncogenic GPCRs. The ONCORNET consortium will offer an extensive multidisciplinary training programme to the ESRs to ensure that they can operate in todays drug discovery programmes. This will include both research (e.g. drug discovery, proteomics, imaging, modelling) and transferable (e.g. entrepreneurship, writing, media training) skill sets that is rarely offered at PhD level. We will train ESRs to develop the next generation of multidisciplinary scientists with skills that are highly demanded by many of todays employers in drug development industries.


Grant
Agency: Cordis | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2016 | Award Amount: 3.59M | Year: 2017

Advanced Microscopy techniques are widely recognized as one of the pillars onto which the research and manufacture of Nanotechnology based products is sustained. At present, the greatest challenge faced by these techniques is the realization of fast and non-destructive tomographic images with chemical composition sensitivity and with sub-10 nm spatial resolution, in both organic and inorganic materials, and in all environmental conditions. Scanning Probe Microscopes are currently the Advanced Microscopy techniques experiencing the fastest evolution and innovation towards solving this challenge. Scanning Probe Microscopes have crossed fundamental barriers, and novel systems exist that show potential unparalleled performance in terms of 3D nanoscale imaging capabilities, imaging speed and chemical sensitivity mapping. The objective of the SPM2.0 European Training Network is to train a new generation of researchers in the science and technology of these novel Scanning Probe Microscopes, in which Europe is currently in a leading position, in order to enforce its further development and its quick and wide commercialization and implementation in public and private research centers and industrial and metrology institutions. The researchers of the network will acquire a solid state-of-the-art multidisciplinary scientific training in this field of research, covering from basic science to industrial applications, which should enable them to generate new scientific knowledge of the highest impact. In addition, they will receive a practical training on transferable skills in order to increase their employability perspectives and to qualify them to access to responsibility job positions in the private and public sectors. The final aim of the network is to consolidate Europe as the world leader in Scanning Probe Microscopy technologies and its emerging applications in key sectors like Materials, Microelectronics, Biology and Medicine.


Patent
Assistance Publique Hopitaux De Paris, French Institute of Health, Medical Research, Institute for Radiological Protection, Nuclear Safety and University of Paris Descartes | Date: 2014-07-09

The present invention relates to the use of gingival fibroblasts-derived products to reduce hair loss and promote hair growth. Specifically, the invention relates to a product derived from gingival fibroblasts to be used in the treatment or prevention of alopecia, as well as in the promotion of natural hair growth and/or in the control of natural hair loss.


Patent
French Institute of Health, Medical Research, University Paris - Sud and Assistance Publique Hopitaux De Paris | Date: 2013-05-22

The present invention relates to methods for diagnosing and treating focal segmental glomerulosclerosis. More particularly, the present invention relates to a method for determining whether a subject is at risk of having or developing a focal segmental glomerulosclerosis (FSGS) comprising the step consisting of determining the level of calcium/calmodulin-dependent serine protein kinase (CASK) in a blood sample obtained from the subject. The present invention also relates to an agent effective to inhibit the binding of CASK to hCD98 present on the surface of podocytes for use in the prevention or treatment of focal segmental glomerulosclerosis (FSGS) in a subject in need thereof.


Patent
University Paris - Sud, French Institute of Health, Medical Research and Assistance Publique Hopitaux De Paris | Date: 2012-07-05

The present invention relates to a culture medium comprising a carbapenem, a carbapenemase activator and a M-type penicillin. It also relates to a method for detecting carbapenem-resistant bacteria in a test sample using said culture medium.


Patent
Aix - Marseille University, French Institute of Health, Medical Research and Institute Jean Paoli & Irene Calmettes | Date: 2012-05-31

The invention relates to antigen peptide derived from the Nectin4 and its use for preventing and treating cancer.


Patent
Institute Gustave Roussy, French Institute of Health, Medical Research, Assistance Publique Hopitaux De Paris, University of Versailles and University Paris - Sud | Date: 2014-01-27

The present invention concerns the V617F variant of the protein-tyrosine kinase JAK2, said variant being responsible for Vaquez Polyglobulia. The invention also relates to a first intention diagnostic method for erythrocytosis and thrombocytosis allowing their association with myeloproliferative disorders, or to the detection of the JAK2 V617F variant in myeloproliferative disorders allowing their reclassification in a new nosological group.


Patent
French Institute of Health, Medical Research, Aix - Marseille University, Institute Jean Paoli & Irene Calmettes and French National Center for Scientific Research | Date: 2014-06-05

The present invention concerns an oligonucleotide modified by substitution at the 3 or the 5 end by a moiety comprising at least three saturated or unsaturated, linear or branched hydrocarbon chains comprising from 2 to 30 carbon atoms, and the use therefore as a medicament, in particular for use for treating cancer.


Patent
French Institute of Health, Medical Research, University Paris - Sud, Assistance Publique Hopitaux De Paris and University Paris Est Creteil | Date: 2015-06-24

The invention relates to a method for diagnosing, staging and/or monitoring a hemoglobin-related disorder such as -thalassemia or a treatment against said hemoglobin-related disorder in a subject in need thereof based on the detection and/or quantification the presence of free -Hb pool in a biological sample obtained from said subject.


Patent
French Institute of Health, Medical Research and University Paris - Sud | Date: 2015-04-21

The present disclosure relates to a Co-029 inhibitor for inhibiting the migration of cancer cells which express Co-029. The disclosure relates to a Co-029 inhibitor for the treatment of cancer and/or the prevention of cancer metastasis and pharmaceutical compositions comprising said inhibitor and provides Co-029 antibodies. The disclosure provides a method for predicting the response of a patient afflicted with or susceptible to be afflicted with cancer to a medical treatment with a Co-029 inhibitor, a method for diagnosing a cancer in a patient and a method for predicting the survival in a cancer patient.


Patent
Institute Jean Paoli & Irene Calmettes, Aix - Marseille University, French Institute of Health, Medical Research, Center Leon Berard and University Claude Bernard Lyon 1 | Date: 2012-03-29

The present invention provides antibodies directed against ICOS or a derivative thereof which neutralize ICOS engagement on Treg by inhibiting the fixation between ICOS and ICOS-L and abrogate proliferation of Treg induced by plasmacytoid dendritic cells. The present invention further provides antibodies directed against ICOS or a derivative thereof which induce IL-10 and IFN production, induce CD4+ T cells proliferation, reduce Tconv proliferation, and increase the immunosuppressive function of Treg.


Patent
French Institute of Health, Medical Research and University of Burgundy | Date: 2015-09-14

The present invention relates to a mutated heat-shock protein 110 (HSP110) lacking its substrate binding domain, which does not exhibit its chaperon activity and/or is not capable of binding to best-shock protein 70 (HSP70) and/or to beat-shock protein 27 (HSP27), but which is capable of binding to a wild-type HSP110. Such a mutated heat-shock protein 110 can be used (i) in methods for proposing survival and/or the response to a treatment of a patient suffering from a cancer, more particularly from a cancer liable to have a microsatellite instability (MSI) phenotype, such as colorectal cancer (CRC), and (ii) for treating cancers.


Patent
French Institute of Health, Medical Research, Aix - Marseille University and Institute Jean Paoli & Irene Calmettes | Date: 2014-03-28

The present invention relates to methods and pharmaceutical compositions for treating breast cancers. In particular, the present invention relates to a method for predicting the survival of a patient suffering from a breast cancer comprising i) determining the expression level of Vangl2 in a tumor sample obtained from the patient, ii) comparing the expression level determined at step i) with a predetermined reference value and iii) providing a poor prognosis when the expression level determined at step i) is higher than the predetermined reference value. The present invention also relates to a method for treating a patient suffering from a breast cancer comprising the steps consisting of i) predicting the survival of the patient according to claim 1 and ii) administering the patient with an anti-Vangl2 antibody or an inhibitor of Vangl2 expression or an inhibitor of the Vangl2-p62 interaction when it is concluded that the patient has a poor prognosis at step i).


Patent
Institute Of Cancerologie Of Louest, University of Angers, French Institute of Health and Medical Research | Date: 2014-11-24

The present invention is in the technical field of breast cancer management, and more particularly relates to the diagnosis and/or prognosing of triple-negative breast cancer (TNBC). The invention is more particularly based on the finding that specific biomarkers are abberantly expressed in patients suffering from a triple-negative breast cancer recurrence, and are highly related to the aggressiveness of this disease, and thus to survival of said patient.


Patent
French Institute of Health, Medical Research, French National Center for Scientific Research, University of Strasbourg, Cornell University, University Paris - Sud and Assistance Publique Hopitaux De Paris Aphp | Date: 2015-05-21

A method for preventing or treating cardiomyopathy due to energy failure in a subject in need thereof is provided. The method comprises administering to the subject a therapeutically effective amount of a vector which comprises a nucleic acid sequence encoding a gene that can reverse energy failure. An exemplary cardiomyopathy is that which is associated with Friedreich ataxia and an exemplary nucleic acid sequence comprises a nucleic acid that encodes frataxin (FXN).


Patent
French Institute of Health, Medical Research, University of Paris Descartes and University Paris - Sud | Date: 2015-06-25

The present invention relates to the treatment and the diagnosis of atherosclerosis, in particular to a miRNA for use in the treatment and the diagnosis of atherosclerosis.


Patent
Alfact Innovation, French Institute of Health, Medical Research and University Paris - Sud | Date: 2013-07-18

This invention concerns a HIP/PAP protein or derivative thereof, for its use in treating or managing cancer and preferentially solid tumors.


Patent
French Institute of Health, Medical Research, French National Center for Scientific Research, University of Paris Descartes, Fondation Image, University Paris - Sud, Assistance Publique Hopitaux De Paris Aphp and University Paris Diderot | Date: 2013-08-02

The present disclosure relates to antagonists of transferrin receptor and compositions and methods of use of said antagonists for treating pathological disorders such as thalassemia disorders


Patent
French Institute of Health, Medical Research, Aix - Marseille University, Institute Jean Paoli & Irene Calmettes and French National Center for Scientific Research | Date: 2013-05-24

The present invention relates to methods for selecting binders by phage display and masked selection. More particularly, the present invention relates to a method for selecting a plurality of binders specific for at least one relevant target comprising screening a phage binder library of binders against the relevant target in presence of a plurality of binders obtained from a library of binders directed against at least one irrelevant target and positively selecting the binders that are specific for the at least one relevant target.


Patent
French Institute of Health, Medical Research, Synchrotron Soleil and University Paris - Sud | Date: 2016-06-01

The present invention relates to a method for measuring a biological value Vb in a liver wherein said method comprises the steps of: a/ applying an infrared radiation having at least a first wave number range between 2800 cm^(1 )and 3000 cm^(1 )to one or more portions, p_(i), of a sample of said liver, b/ detecting the intensity of the radiation after it has passed through each of one or more portions, p_(i), and generating a signal related to the detected intensity. c/ processing the generated signal(s) to calculate an average value v_(a); d/ comparing said average value V_(a )to a standard to obtain the biological value Vb.


Grant
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: SC1-PM-11-2016-2017 | Award Amount: 6.00M | Year: 2017

Current orthopaedic treatments permit spontaneous bone regeneration to unite and heal 90% bone injuries. Non-union associates pain and disability, often requiring biological enhancement. Regenerative medicine research suggests to the general public that alternative treatments based on advanced therapy medicinal products (ATMP) are already available. However, early clinical trials only explore its potential benefit. Underreported results and absence of early trial confirmation in adequately powered prospective randomized clinical trials (RCT) indicate that evidence is not available to transfer any technique into routine clinical application. This ORTHOUNION Project was developed from FP7-Project (REBORNE). Its results confirmed 92% bone healing rate (Gmez-Barrena et al, 2016 submitted manuscript) with an autologous ATMP of GMP expanded bone marrow derived human MSC in non-unions, where the reported bone healing rate after surgery with standard bone autograft is 74%. Any further development requires adequately powered prospective RCTs. This will be the main aim of ORTHOUNION: to assess clinically relevant efficacy of an autologous ATMP with GMP multicentric production in a well-designed, randomized, controlled, three-arm clinical trial under GCP, versus bone autograft, gold-standard in fracture non-unions. A non-inferiority analysis will evaluate if cell dose can be lowered. ATMP has been authorized by the National Competent Authorities of the participating countries in 3 previous trials (REBORNE) and will be monitored by ECRIN-ERIC to ensure quality and credibility of RCT results. Secondary aims include innovative strategies to increase manufacturing capacity and lower costs to pave translation into routine clinical treatments, biomaterial refinement to facilitate surgery, personalized medicine supportive instruments for patient selection and monitoring, and health economic evaluation. Results in this project may help define the future of bone regenerative medicine


Heisenberg C.-P.,Institute of Science and Technology Austria | Bellaiche Y.,French Institute of Health and Medical Research
Cell | Year: 2013

During development, mechanical forces cause changes in size, shape, number, position, and gene expression of cells. They are therefore integral to any morphogenetic processes. Force generation by actin-myosin networks and force transmission through adhesive complexes are two self-organizing phenomena driving tissue morphogenesis. Coordination and integration of forces by long-range force transmission and mechanosensing of cells within tissues produce large-scale tissue shape changes. Extrinsic mechanical forces also control tissue patterning by modulating cell fate specification and differentiation. Thus, the interplay between tissue mechanics and biochemical signaling orchestrates tissue morphogenesis and patterning in development. © 2013 Elsevier Inc.


Proville R.D.,French Institute of Health and Medical Research | Proville R.D.,The Interdisciplinary Center | Proville R.D.,University of Strasbourg
Nature neuroscience | Year: 2014

Sensorimotor integration is crucial to perception and motor control. How and where this process takes place in the brain is still largely unknown. Here we analyze the cerebellar contribution to sensorimotor integration in the whisker system of mice. We identify an area in the cerebellum where cortical sensory and motor inputs converge at the cellular level. Optogenetic stimulation of this area affects thalamic and motor cortex activity, alters parameters of ongoing movements and thereby modifies qualitatively and quantitatively touch events against surrounding objects. These results shed light on the cerebellum as an active component of sensorimotor circuits and show the importance of sensorimotor cortico-cerebellar loops in the fine control of voluntary movements.


Yusupova G.,University of Strasbourg | Yusupova G.,French Institute of Health and Medical Research | Yusupov M.,University of Strasbourg | Yusupov M.,French Institute of Health and Medical Research
Annual Review of Biochemistry | Year: 2014

The high-resolution structure of the eukaryotic ribosome from yeast, determined at 3.0-A resolution, permitted the unambiguous determination of the protein side chains, eukaryote-specific proteins, protein insertions, and ribosomal RNA expansion segments of the 80 proteins and 5,500 RNA bases that constitute the 80S ribosome. A comparison between this first atomic model of the entire 80S eukaryotic ribosome and previously determined structures of bacterial ribosomes confirmed early genetic and structural data indicating that they share an evolutionarily conserved core of ribosomal RNA and proteins. It also confirmed the conserved organization of essential functional sites, such as the peptidyl transferase center and the decoding site. New structural about eukaryote-specific elements, such as expansion segments and new ribosomal proteins, forms the structural framework for the design and analysis of experiments that will explore the eukaryotic translational apparatus and the evolutionary forces that shaped it. New nomenclature for ribosomal proteins, based on the names of protein families, has been proposed. Copyright © 2014 by Annual Reviews.


Coulouarn C.,French Institute of Health and Medical Research | Clement B.,University of Rennes 1
Journal of Hepatology | Year: 2014

Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are the most common types of primary tumors in the liver. Although major advances have been made in understanding the cellular and molecular mechanisms underlying liver carcinogenesis, HCC and ICC are still deadly cancers worldwide waiting for innovative therapeutic options. Growing evidence from the literature highlight the critical role of the tumor cell microenvironment in the pathogenesis of cancer diseases. Thus, targeting the microenvironment, particularly the crosstalk between tumor cells and stromal cells, has emerged as a promising therapeutic strategy. This strategy would be particularly relevant for liver cancers which frequently develop in a setting of chronic inflammation and microenvironment remodeling associated with hepatic fibrosis and cirrhosis, such processes in which hepatic stellate cells (HSC) greatly contribute. This review brings a genomic point of view on the alterations of the cellular microenvironment in liver cancers, particularly the stromal tissue within tumor nodules, emphasizing the importance of the crosstalk between tumor cells and stromal cells, notably activated HSC, in tumor onset and progression. Furthermore, potential therapeutic modalities of targeting the stroma and HSC are discussed. © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.


Grant
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: INFRADEV-3-2015 | Award Amount: 4.95M | Year: 2015

BBMRI-ERIC: the Biobanking and BioMolecular resources Research Infrastructure - European Research Infrastructure Consortium, aims to establish, operate and develop a Pan-European distributed research infrastructure in order to facilitate the access to biological resources as well as facilities and to support high quality biomolecular and biomedical research. The ADOPT BBMRI-ERIC proposal aims at boosting and accelerating implementation of BBMRI-ERIC and its services. Its main deliverables are designed to complete or launch the construction of key Common Services of the Research Infrastructure as required for ESFRI-projects under implementation, reflecting the targets of the European Research Area (ERA). One of the challenges in the post-genomic era is the research on common complex diseases, such as cancer, diabetes and Alzheimers disease. Revealing these diseases will depend critically on the study of human biological samples and data from large numbers of patients and healthy individuals. The EUs ageing population is will result in an increase in many of those diseases and consequently an increased healthcare expenditure for senior citizens. BBMRI-ERIC is a specific European asset having become a fundamental component in addressing the ongoing and future requirements particularly of Europes health service frameworks, including competitiveness and innovativeness of health-related industries. Its implementation is essential for the understanding of the diversity of human diseases, biological samples and corresponding data, which are required for the development of any new drug or diagnostic assay and are, therefore, critical for the advancement in health research, ultimately leading to personalised medicine. BBMRI-ERIC will provide a gateway access to the collections of the European research community, expertise and services building on the outcome of ADOPT BBMRI-ERIC.


Patent
Bio Rad Innovations, Ariana Pharmaceuticals, French National Center for Scientific Research, Assistance Publique Hopitaux De Paris, French Institute of Health and Medical Research | Date: 2012-02-09

The application concerns means for predicting whether a subject infected with one or more HCVs has a high probability of responding to an anti-HCV treatment which will comprise the administration of interferon and of ribavirin or whether, in contrast, that subject has a high probability of not responding to that anti-HCV treatment. The means of the invention in particular involve assaying the levels of expression of selected genes, said selected genes being:


Patent
French Institute of Health, Medical Research and University Claude Bernard Lyon 1 | Date: 2012-01-27

The present invention concerns an in vitro method for determining cancer prognosis for a patient suffering from early-stage or low-grade cancer, said method comprising measuring the expression level of ERR in a biological sample comprising cancer cells. The invention further pertains to an in vitro method for determining bone metastases prognosis for a patient suffering from bone metastases comprising measuring the expression level of ERR. Finally, the invention pertains to in vitro methods for selecting a patient suffering from cancer, and/or from cancer-derived metastasis, suitable to be treated with a preventive/aggressive therapy.


Patent
Cornell University, French Institute of Health, Medical Research, French National Center for Scientific Research and University of Strasbourg | Date: 2014-01-31

The present invention relates to a method for preventing or treating cardiomyopathy due to energy failure in a subject in need thereof, comprising administering to said subject a therapeutically effective amount of a vector which comprises a nucleic acid sequence of a gene that can restore energy failure. More particularly, the invention relates to a method for preventing or treating a cardiomyopathy associated with Friedreich ataxia in a subject in need thereof, comprising administering to said subject a therapeutically effective amount of a vector which comprises a frataxin (FXN) encoding nucleic acid.


Patent
French Institute of Health, Medical Research, University of Paris Descartes and Assistance Publique Hopitaux De Paris Aphp | Date: 2013-07-12

The present invention relates to a method for predicting the survival time of a patient suffering from a solid cancer comprising i) determining in a tumor sample obtained from the patient the gene expression level of at least 7 genes selected from the group consisting of CCR2, CD3D, CD3E, CD3G, CD8A, CXCL10, CXCL11, GZMA, GZMB, GZMK, GZMM, IL15, IRF1, PRF1, STAT1, CD69, ICOS, CXCR3, STAT4, CCL2, and TBX21, ii) comparing every expression level determined at step i) with their predetermined reference value and iii) providing a good prognosis when all expression levels determined at step i) are higher than their predetermined reference values, or providing a bad prognosis when all expression levels determined at step i) are lower than their predetermined reference values or providing an intermediate prognosis when at least one expression level determined value is higher than its predetermined value. The method is also particularly suitable for predicting the responsiveness of the patient to a treatment.


Patent
Edap Tms France, French Institute of Health and Medical Research | Date: 2014-10-23

The object of the invention relates to an apparatus for the thermal treatment of biological tissues by means of the application of focused ultrasound waves, the apparatus including:


Patent
French Institute of Health, Medical Research, Association Francaise Contre Les Myopathies, University of Strasbourg and French National Center for Scientific Research | Date: 2012-08-29

The present invention relates to an ex vivo method for preparing induced paraxial mesoderm progenitor (iPAM) cells, said method comprising the step of culturing pluripotent cells in an appropriate culture medium comprising an effective amount of an activator of the Wnt signaling pathway and an effective amount of an inhibitor of the Bone Morphogenetic Protein (BMP) signaling pathway.


Patent
French Institute of Health, Medical Research, University of Strasbourg and French National Center for Scientific Research | Date: 2012-11-22

The present invention relates to agent selected from the group consisting of an anti-S100B antibody, an anti-S100B aptamer or an inhibitor of S100B gene expression for use in a method for reducing airway hyperresponse in a subject in need thereof. The present invention also relates to a method for determining whether a subject is at risk of having or developing an airway hyperresonse comprising determining the level of S100B protein in a biological sample obtained from said subject.


Patent
Center Leon Berard, University Claude Bernard Lyon 1, Hospices Civils De Lyon, French Institute of Health, Medical Research and French National Center for Scientific Research | Date: 2012-12-17

A method for selecting in vitro compounds is capable of potentiating the effect of a DNA damage inducing chemotherapy agent for the treatment of cancer, and includes selecting compounds inhibiting the interaction between MyD88 and ERK MAP KINASE.


Patent
Center Leon Berard, French National Center for Scientific Research, French Institute of Health, Medical Research and University Claude Bernard Lyon 1 | Date: 2013-07-26

Detection of the ER/Src/PI3K complex by a Proximity ligation assay as prognostic and theranostic marker in breast cancer.


Patent
Center Leon Berard, University Claude Bernard Lyon 1, French Institute of Health and Medical Research | Date: 2013-07-01

Method for identifying a breast cancer likely to respond to treatment with everolimus comprising the following steps: Measuring the level of expression of the LKB 1 gene in a breast tumour sample previously taken from a breast cancer patient, Classifying the breast cancer as likely to respond to treatment with everolimus if the LKB1 gene is under-expressed in said breast tumour sample.


Patent
Cytune, French Institute of Health and Medical Research | Date: 2016-07-19

The present invention relates to an immunocytokine comprising (a) a conjugate, and (b) an antibody or a fragment thereof directly or indirectly linked by covalence to said conjugate, wherein said conjugate comprises (i) a polypeptide comprising the amino acid sequence of the interleukin 15 or derivatives thereof, and a polypeptide comprising the amino acid sequence of the sushi domain of the IL-15R or derivatives thereof; and uses thereof.


Patent
University of Strasbourg, French National Center for Scientific Research, French Institute of Health and Medical Research | Date: 2014-10-20

The present disclosure relates to an inhibitor of Dynamin 2 for use in the treatment of centronuclear myopathies. The present disclosure relates to pharmaceutical compositions containing Dynamin 2 inhibitor and to their use for the treatment of centronuclear myopathies. It also deals with a method for identifying or screening molecules useful in the treatment of a centronuclear myopathy.


Grant
Agency: Cordis | Branch: H2020 | Program: RIA | Phase: NMP-06-2015 | Award Amount: 4.99M | Year: 2016

FOLSMART will bring to phase I clinical trials novel folate-based nanodevices (FBN) for the treatment of rheumatoid arthritis (RA). These nanodevices for folic acid (FA)-mediated targeting of activated macrophages showed improved clinical scores in a mouse model of RA when compared to methotrexate (MTX), a first-line drug therapy for the treatment of RA. In this way, FBN will be benchmarked against this drug. MTX has significant associated toxicity and second line biological therapies poses a great economic burden to hospital/public health systems. In parallel, nanodevices encapsulating Sulfasalazine (SSZ), will be tested. SSZ is a second line indication for the treatment of RA, unresponsive to MTX or MTXintolerant patients. Furthermore, FOLSMART propose the optimization of mechanisms for the release of the drugs, through pH and temperature sensitive nanodevices. An exploitation and business plans will be elaborated. In parallel, initial economic evaluation of all proposed treatments will be performed to validate these claims. Specific technological objectives of FOLSMART will be: Good Manufacturing Practice (GMP) production of the FBN based therapies which have been positively bench-marked in the previous FP7 European project NANOFOL in comparison with the use of MTX in a RA mouse model: -Liposomal MTX and SSZ with FA-neck domain peptide as targeting agent -Nanoparticles from HSA-FA/MTX conjugates and SSZ -Optimization of mechanisms of drug release and application to other fields Pre-clinical development on RA models -Toxicology and pharmacokinetics, to determine tolerability and efficacy benefit in two animal models rat and dog, under Good Laboratory Practice (GLP) standards -Genotoxicity and Carcinogenicity Phase I clinical trials of the best therapies bench marketed against MTX -Nanodevices with MTX and SSZ will offer improved tolerance and greater efficacy meaning that patients who do not do well on MTX will have cost-effective alternatives


Patent
French Institute of Health, Medical Research and University of Rennes 1 | Date: 2012-10-31

The present invention relates to testicular germline markers and their use for predicting the presence or not of reproductive cells in testis of an infertile or hypo fertile male subject.

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