Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2012.2.3.2-2 | Award Amount: 7.84M | Year: 2013
Extensive clinical and epidemiological data clearly shows that chronic periodontal disease (PD), the most prevalent infectious inflammatory disease of mankind, is strongly linked to systemic inflammatory diseases such as cardiovascular diseases (CVD) , rheumatoid arthritis (RA) , and chronic obstructive pulmonary disease (COPD) . Taking into account that up to 30% of the adult population worldwide suffers from severe periodontitis , the impact of this disease on human health is immense and has been recognized by World Health Organization . Nevertheless, in many EU countries PD is a neglected disease, both by the population in general and health-care personnel. Often this negligence comes to the point that, like a hair-loss, the tooth-loss due to periodontitis is still considered as a normal inevitable event associated with aging. To combat this misconception and conceive novel approaches to prevent and/or treat CVD, RA, and COPD we will explore highly innovative ideas that these non-communicable diseases are at least aggravated, if not initiated, by periodontal infection. Results emanating from our project will: i) elucidate a relationship between the presence of specific periodontal pathogens and severity of systemic diseases; ii) show that extensive periodontal treatment improves clinical parameters of investigated systemic diseases; iii) reveal the impact of eradication of specific periodontal pathogen on the level of inflammatory markers; iv) develop novel, periodontal-pathogen specific bactericidal compounds based on periodontal glutaminyl cyclase (QC), the enzyme essential for these pathogens vitality. This will reduce mortality and ameliorated quality of life of CVD, RA, and COPD patients. All of these will be possible based on the knowledge of mechanisms beyond the causative links between specific pathogen driven periodontal disease and CVD, RA, and COPD revealed by research program outlined in this project.
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH-2009-2.4.4-1 | Award Amount: 7.77M | Year: 2009
Myasthenia Gravis (MG) is a heterogeneous rare autoimmune neurological disease affecting the neuromuscular junction (NMJ). The molecular events causing and maintaining MG are still unknown and current treatments do not lead to remission and entail considerable side-effects stressing the need for improved therapies. We will address the: 1. Natural course of disease: determine factors associated with disease onset and/or affecting the course of disease and patients quality of life in subgroups of MG patients including children, twins, females and elderly patients. 2. Etiology of MG: identify new genetic, epigenetic and environmental risk factors and investigate immunological key molecules associated with MG onset. 3. Pathogenic mechanisms at the NMJ: a) study molecular changes in the NMJ by proteomic, genetic, epigenetic and microRNA analyses in MG patients and experimental models; b) analyze morphological changes at the NMJ in mouse models expressing YFP nerves and mice transgenic for mini-agrin; c) evaluate the capacity of muscle cell satellites from MG patients to regenerate muscle and form new endplates in immunodeficient mice. 4. New diagnostic and monitoring assays: a) identify pathogenic and protective factors in MG sera; b) improve the sensitivity of current assays; c) Identify new biomarkers associated with different MG subgroups by proteomic and microRNA analyses; d) Identify patients response to treatment and liability to side effects by pharmacogenomic analyses. 5. Novel therapies: a) study new cell-based therapies aimed at regulating the autoimmune response by regulatory T cells or mesenchymal stem cells in humanized mice; b) immunoadsorb pathogenic antibodies; c) test non-cell based immmunomodulatory therapies; d) target epigenetic regulators. This multidisciplinary project linking basic researchers with clinical neurologists, SMEs and several European patient associations should favor a translational approach for improved MG management
Agency: European Commission | Branch: FP7 | Program: CP | Phase: ICT-2011.5.5 | Award Amount: 3.33M | Year: 2012
The objective of the LITERACY project is to create an advanced online portal, which will aid both dyslexic youths and adults. The Portal will provide personalized e-learning programs, useful tools and methods for helping people with dyslexia to improve their abilities in reading, writing and then function in society. The Portal will also provide entry to an accessible online community of peers. Employing novel modelling algorithms the system will assess the users level of literacy and particular strengths/weaknesses in learning. It will on this basis automatically adjust to provide the required personalized services for that specific user. A specialized interface and Community Zone with programs and services will improve users skills, drastically simplifying otherwise complicated tasks. This will be done by utilizing advanced novel tools which will be integrated with both existing and adapted ICT tools and hardware. Dyslexic users will be able to access this portal independently and receive real-time feedback on their progress. The Portal will be based on input of content by educational professionals in both EU and Associate countries, providing an array of levels and in several languages.\nThe Portal will empower and support dyslexic youth and adults to help themselves succeed in literacy related achievements, ultimately strengthening their success and inclusion in school, university, work and their social lives.
Agency: European Commission | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2014-ETN | Award Amount: 3.89M | Year: 2015
The human visual brain can learn and adapt to change, which solves many of the problems posed by an ever-changing visual environment. However, to maintain a consistent overall representation of the visual world, the brain also has to retain previously acquired neuronal mechanisms. The key is to strike a balance between plasticity and stability. Increasing our knowledge about the stability and plasticity of the visual brain has tremendous potential for innovation in health care and high-tech industry: 1) rehabilitation, treatments and detection of disease can be developed and refined based on knowing how the brain changes as a result of visual loss or neural dysfunction; 2) it can inspire the development and implementation of artificial intelligence, such as adaptive automated vision systems. However, our present knowledge of the adaptive capacity of the human brain is incomplete and largely qualitative in nature. This limits translation into significant applications. To overcome this, NextGenVis Research Network for training the Next Generation of European Visual Neuroscientists will aim its research and training efforts on teaching young researchers in how to a) acquire new, quantitative knowledge on the adaptive properties of the visual brain in health and disease with a strong focus on the neurocomputational basis and b) apply this new knowledge to boost innovation in health care and technology. Our pan-European team of academic, health care and private sector partners is ideally suited to accomplish this as it bundles and focuses unique European expertise and resources in brain imaging, psychology, neurology, ophthalmology and computer science. Importantly, the positive impact of this network will extend beyond the current focus on vision and will last long after the funding period. It will continue to link together a team of highly skilled researchers who will inspire each other to excel in visual neuroscience and its applications.
Agency: European Commission | Branch: FP7 | Program: CP-FP | Phase: HEALTH.2013.2.3.1-2 | Award Amount: 7.77M | Year: 2013
Though of tremendous benefit, the overuse of antibiotics has lead to the emergence of antibiotic resistance and may cause adverse events that impact on patient healthcare. Current diagnostic tools for facilitating the appropriate use of antibiotics in patients are inadequate. We will establish a broad-based strategy (not limited to a particular antibiotic group) that can be implemented on a broad scale to increase the effectiveness of antimicrobial therapy, reduce adverse events, and help limit the emergence of antimicrobial resistance in children and adults. At the heart of the TAILORED-Treatment project is a prospective clinical study in which we will recruit 1200 patients (>2000 patient samples) presenting with respiratory tract infections and/or sepsis. Patient cohorts will include equal representation of genders, children and adults. State-of-the-art molecular technologies will be applied to characterize host-pathogen interactions at the genomic, transcriptomic, proteomic and clinical level, resulting in a large-scale and unique multi-dimensional dataset. The consortium partners will develop new computational tools to interrogate this data, in order to provide new insights into personalized host-pathogen interactions, including the discovery of novel biomarkers for physicians to use in patient diagnosis and disease monitoring. Concurrently, using this data, we will construct a predictive personalized treatment algorithm that will lead to informed and personalized antimicrobial treatment regimens (indication, dosage, and duration) that are tailored to the needs (type of infection, presence of novel biomarkers etc) of children and adults presenting with respiratory infections and sepsis. This unique multi-dimensional dataset and personalized predictive treatment algorithm will be built into an easily navigable web-based, free-to-use, decision support system for use by physicians to explore and assist in patient-tailored antimicrobial treatment decisions.
Agency: European Commission | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2012-ITN | Award Amount: 3.06M | Year: 2012
Vaccines are the most cost-effective health interventions available (WHO). The impact of vaccination on the health of the worlds population cannot be overstressed. Vaccinolgy is the multidisciplinary discipline of developing vaccine interventions it combines knowledge from basic sciences, medical sciences, public health and social sciences. Ideally a vaccinologists would be able to have a general overview of all disciplines involved but at the same time be able to zoom in on its own discipline. There is hardly any formal training to become a vaccinologist in the world and none such training exists at a PhD level in Europe. The need for a program to train vaccinologists is apparent and recognised . The vaccine industry is a largely European based industry. Investing in the future of this industry by training the next generation vaccinologists will boost Europeans economy will provide high quality employment and will sustain Europeans competitiveness. Clearly there are public health and economic reasons to invest in a training program training the European vaccinologists of the future.
German Cancer Research Center, Hebrew University of Jerusalem and Hadassah Medical Organization | Date: 2013-10-16
The present invention is concerned with measures for tumor therapy. In particular, contemplated is an inhibitor of Receptor for Advanced Glycation-End products (RAGE) for use in treating and/or preventing inflammation- and/or damage-induced cancer. The invention, furthermore, relates to a medicament comprising said inhibitor of RAGE and, preferably, a pharmaceutically acceptable carrier. Further, the invention encompasses a method for identifying a subject in need of treatment with an inhibitor of RAGE, comprising determining in a sample from said subject the amount of RAGE, comparing said amount of RAGE determined in step a) with a reference amount, and identifying a subject in need of treatment with an inhibitor of RAGE. The invention also relates to a device for identifying a subject in need of treatment with an inhibitor of RAGE, as well as a kit adapted to carry out the method of the present invention, said kit comprising instructions for carrying out the aforementioned method.
Agency: European Commission | Branch: FP7 | Program: ERC-SG | Phase: ERC-SG-LS7 | Award Amount: 1.65M | Year: 2013
Radioactively labeled deoxyglucose and choline are the leading molecular imaging probes for positron emission tomography (PET). The clinical applications for this imaging modality include brain function, cardiac imaging, and inflammation, along with oncological applications which are taking the lead. The radiation exposure associated with these examinations is limiting the use of this powerful technology in repeated examinations, in specific populations (pregnant women and children), as a screening tool for the wide population, and as a clinical research tool. Hyperpolarized magnetic resonance imaging (MRI) is an evolving pre-clinical and clinical imaging modality which is non-invasive and non-radioactive. As in PET, the molecular imaging probe used is at the heart of this examination. Originally developed for the purpose of distinguishing the metabolic products of the injected molecular probe, our group, in collaborations with researchers abroad, is a pioneer in showing that direct imaging of specific molecular probes (stable isotope labeled choline and glucose analogs) with hyperpolarized MRI is capable of showing specific tissue uptake, a pre-requisite for diagnostic imaging. The purpose of the current proposal is to establish hyperpolarized MRI capabilities in our own lab and reach two general goals: 1) to use various physiological and pharmacological models to further establish and characterize the conditions in which non-radioactive choline and glucose analogs and derivatives can be useful as imaging probes; and 2) to investigate further the molecular probe that is best suitable for these imaging applications in terms of pharmacokinetics, metabolism, and imaging efficiency. Our focus will be on 1) the actual chemical entity of the probes - where citicoline and deoxyglucose are promising candidates; and 2) the stable isotope labeling strategy. The overriding goal is to aid in translation of this pre-clinical imaging approach to clinical use.
Agency: European Commission | Branch: FP7 | Program: MC-IRG | Phase: FP7-PEOPLE-2009-RG | Award Amount: 100.00K | Year: 2011
T-lymphocytes require calcium entry though the plasma membrane for their activation and function. Recently, several routes for calcium entry through the T cell plasma membrane after activation have been described. These include CRAC channels (Calcium Release of Activated Channels), TRP channels (Transient Receptor Potential) and inositol-1,4,5-trisphosphate receptors (IP3R). Herein we are proposing the emergence of a new fourth route for calcium entry, composed of Cav channels (also known as L-type voltage gated calcium channels) and their regulator scaffold protein AHNAK1 (AHNAK/Desmoyokin). In excitable cells, such as neurons or muscle cells, Cav calcium channels constitute the major route for calcium entry. We have previously published that both helper (CD4\) and killer (CD8\) T cells express high levels of Cav1 alpha1 subunits (alpha 1S, -1C, -1D and -1F) and AHNAK1 after their differentiation and require these molecules for calcium entry during an immune response. This proposal aims to study the molecular mechanism by which this pathway is induced and functions. My preliminary evidence suggest that Cav channel calcium currents are induced by TCR stimulation, not by voltage depolarization, as described in excitable cells. Further studies proposed here are required to study this phenomenon. In this proposal, we will describe the observations and open questions, which ultimately suggests the involvement of multiple consecutive routes for calcium entry into lymphocytes, one of which is apparently mediated by Cav channels and AHNAK1.
Agency: European Commission | Branch: FP7 | Program: MC-IEF | Phase: FP7-PEOPLE-2012-IEF | Award Amount: 164.38K | Year: 2013
Orientation in space, time, and person is the essence of the behaving self, and the bedrock of neurological and psychiatric mental status examination. States of disorientation may be the hallmark manifestation of several neuropsychiatric disorders. Despite orientations central role in health and disease, orientation has almost never been a subject for neuroscientific research. Consequently, there is uncertainty as to the cognitive and clinical meaning of orientation, and its role in the psychopathology of several major neuropsychiatric disorders, such as dissociative disorders, misidentification syndromes, or Alzheimers disease and amnesia syndromes. Here we hypothesize that (1) orientation is a distinct cognitive function and that (2) orientations over the different domains and clinical conditions rely on shared psychological and neural mechanisms. We propose to investigate the ability of humans to orient themselves in time, space and person, based on a unified referential system. We will examine whether orientations in the different domains are placed on a common vectorial trajectory, using mental tasks, functional imaging (with new analyses methods as based on machine learning and networks research) and computational neuroscience in healthy individuals and those affected by disorders of disorientation. While presently we do not have any established definition of the role of orientation in central pathologies our results might therefore define the orientation system and its role in neuropsychiatric disorders in which orientation is disturbed. This may be important for the recent challenge of our orientation system by the cyber world, which changes our habitual relations to space, time, and people. Finally, the study results will be used in order to established neuroimaging based tools for diagnosis, monitoring and management of disorientation disorders such as Alzheimers disease and dissociative disorders.