Universitaetsklinikum Heidelberg | Date: 2016-09-27
The present invention relates to the field of gastroenterology and, more particular, to the field of intestinal diseases. More specifically, it concerns uses and methods for the treatment of inflammatory bacterial diseases of the intestine. In particular, it relates to diseases that are associated with bacterial invasion of the intestinal mucus, including, inflammatory bowel diseases, and infectious bacterial diseases. Therefore, the present invention provides agents, a pharmaceutical composition and a kit for treating said diseases. It further relates to a use and a method for treating invasive bacterial diseases of the large intestine.
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: PHC-03-2015 | Award Amount: 6.19M | Year: 2016
Understanding mechanisms underlying comorbid disorders poses a challenge for developing precision medicine tools. Psychiatric disorders are highly comorbid, and are among the last areas of medicine, where classification is driven by phenomenology rather than pathophysiology. We will study comorbidity between the most frequent psychiatric conditions, ADHD, mood/anxiety, and substance use disorders, and a highly prevalent somatic disease, obesity. ADHD, a childhood-onset disorder, forms the entry into a lifelong negative trajectory characterized by these comorbidities. Common mechanisms underlying this course are unknown, despite their relevance for early detection, prevention, and treatment. Our interdisciplinary team of experts will integrate epidemiologic/genetic approaches with experimental designs to address those issues. We will determine disease burden of comorbidity, calculate its socioeconomic impact, and reveal risk factors. We will study biological pathways of comorbidity and derive biomarkers, prioritizing two candidate mechanisms (circadian rhythm and dopaminergic neurotransmission), but also leveraging large existing data sets to identify new ones. A pilot clinical trial to study non-pharmacologic, dopamine-based and chronobiological treatments will be performed, employing innovative mHealth to monitor and support patients daily life. Integration of findings will lead to prediction algorithms enhancing early diagnosis and prevention of comorbidity. Finally, we will screen to repurpose existing pharmacological compounds. Integrating complementary approaches based on large-scale, existing data and innovative data collection, we maximize value for money in this project, leading to insight into the mechanisms underlying this comorbidity triad with its huge burden for healthcare, economy, and society. This will facilitate early detection and non-invasive, scalable, and low-cost treatment, creating opportunities for substantial and immediate societal impact.
Agency: European Commission | 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.
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: PHC-23-2014 | Award Amount: 5.99M | Year: 2015
ADVOCATE brings together top principal investigators from prestigious universities, the public sector, and the private sector to address the most common diseases affecting humanity, as measured by the recent Global Burden of Disease Study. ADVOCATE strives to optimise delivery of oral health and wellbeing to the population in EU Member States. This requires a change in oral health care delivery towards prevention. The change will be achieved by developing a model that promotes a preventive rather than restorative oral health care system: The oral health care model 2020. As the oral health care delivery system is not as overly complex as other health care systems, the oral health care model 2020 may serve as a blueprint for other health care system reforms. The development of this model requires intensive information exchange and engagement of stakeholders to establish a set of key-indicators. These indicators will be used to benchmark health care performance on practice as well as system level. Two types of evidence-based indicators will be selected: Quantitative and qualitative indicators that allow measuring and influencing of either intrinsic motivation or extrinsic motivation incentives towards a patient centred, resilient and prevention oriented oral health care system. ADVOCATE will test this model in a natural environment, and provide evidence-informed policy measures towards its implementation, both for oral health care systems as well as other health care systems. Given the comprehensiveness of the topic, ADVOCATE uses a targeted approach that is entirely focused on the five major root-causes underlying the current suboptimal performance of oral health care systems. Moreover, ADVOCATE has confirmed access to data of eight European oral health care databases; it is well connected to existing initiatives and networks, and has ample support from preventive oriented industry, as exemplified by the financial support provided for the final conference.
Agency: European Commission | 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.
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: SC1-PM-09-2016 | Award Amount: 6.00M | Year: 2017
Ischemic stroke (IS), caused by occlusion of arteries that supply blood to the brain, remains a leading cause of mortality and morbidity in the world. Disruption of blood and oxygen supply to the brain leads to neuronal death in the ischemic core within minutes. The hypoperfused tissue surrounding the ischemic core, the penumbra, is at high risk for infarction over time but still salvageable. Neuroprotective bridging, sustaining the penumbra until reperfusion, may widen the therapeutic window, make recanalization treatments accessible to more patients and improve overall IS outcomes. As ischemic cell death is primarily mediated by hypoxia, increasing oxygen supply to the penumbra seems THE logical approach. In animal models of IS, normobaric hyperoxygenation (NBHO) significantly increased penumbral oxygen pressure and attenuated brain injury when initiated early after onset of ischaemia and vessel occlusion was transient (35 to 50% infarct volume reduction). The PROOF project now seeks to demonstrate that NBHO (high-flow 100% oxygen at >45 L/min via a non-rebreather mask, or FiO2=1.0 for intubation/ventilation) reduces infarct growth from baseline to 24 hours compared to standard treatment if administered 3 hours after onset of anterior circulation IS, in patients with proximal vessel occlusion and salvageable tissue at risk. The study is multi-center, adaptive phase-IIb, randomized, open-label with blinded-endpoint (PROBE design). The primary efficacy criterion will be infarct growth from baseline to 24 hours. Secondary endpoints will be NIHSS 24h, categorical shift in the pre-stroke modified Rankin Score, QoL and cognition at day 90. Potential surrogate biomarkers, health economics and societal impacts will be assessed. If NBHO proves its neuroprotective potential in this selected population, phase-III trials in all IS patients may be undertaken. Considering its low costs and ease of use, NBHO may impact stroke care worldwide.
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: PHC-15-2015 | Award Amount: 6.70M | Year: 2016
Spinal cord injury is a severe and devastating neurological disorder that leaves patients with permanent paralysis of the body. No treatment is available today to regenerate interrupted nerve fibers and repair the damaged spinal cord. The incidence of spinal cord injury is about newly injured 10000 people per year in the EU, and due to an almost normal life expectancy more than 200000 patients are living with a spinal cord injury in the EU. The impact on the individual quality of life is high, and social costs are enormous. Recent preclinical research in animal models succeeded to greatly enhance axonal sprouting, fiber regeneration and neuroplasticity following injuries of brain and spinal cord. These results warrant translation now to patients suffering from acute spinal cord injury. A previous phase I clinical study using intrathecal application of a nerve fiber growth promoting antibody against the growth inhibitory protein Nogo-A has shown in patients with complete spinal cord injury that this treatment is safe and well tolerated. The present study will enroll patients with various degrees of complete to incomplete acute spinal cord injury for a double-blind, placebo-controlled trial to test the efficacy of this antibody therapy to improve motor outcome and quality of life of tetraplegic patients. The enrollment of patients with different degrees of spinal cord injury is considered essential to reveal drug activity and eventual proof of concept in a broad patient population. Advancements in clinical trial design, improved prediction algorithms of clinical outcomes and development of surrogate markers (in cerebro-spinal fluid/serum and by neuroimaging) will allow for scrutinizing the effectiveness of this novel treatment in an unprecedented way. A positive outcome of this trial will represent a breakthrough for the future therapy of spinal cord injuries and beyond (traumatic brain injury, stroke, multiple sclerosis).
Agency: European Commission | Branch: H2020 | Program: MSCA-ITN-ETN | Phase: MSCA-ITN-2014-ETN | Award Amount: 3.85M | Year: 2015
Viral infections are a major cause of disease, mortality and economic losses worldwide. Antiviral therapy is an essential instrument to control virus infections. At present, however, licensed antiviral drugs have been developed only against a limited number of viruses (e.g. HIV, HCV, influenza, herpesviruses). There is a clear and unmet need for antiviral drugs to treat infections with other important human pathogens. Europe needs well-trained experts with multidisciplinary skills to advance the antiviral drug development field. However, few, if any, European universities or research institutes have the ability to deliver an intersectoral training programme that covers the broad spectrum of disciplines important for antiviral drug development. The ANTIVIRALS partnership has been established to fill this gap. It consists of six outstanding European academic partners and four industrial partners (two large R&D companies, of which one is specialized in antiviral drug discovery and development, and two SMEs), and two partner organisations (incl. one SME specialised in education). All partners are leaders in their field, ensuring state-of-the-art training possibilities, and their skills are highly complementary. ANTIVIRALS aims to introduce 15 ESRs to state-of-the-art knowledge and technology applied in antiviral drug development through both local and network-wide training activities. Individual research projects, research training workshops and intersectoral secondments will be supplemented with complementary skills courses and dissemination activities to improve career development and perspectives. The industrial partners are actively involved in the entire programme and will organize an industry-oriented conference aimed at further bridging the gap between academia and industry. Thus, ANTIVIRALS offers talented researchers a multidisciplinary and intersectoral training programme and prepares them for a future leading role in antiviral drug development in Europe.
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: PHC-14-2015 | Award Amount: 6.00M | Year: 2016
The objective of MYOCURE is to develop an innovative gene therapy platform to cure rare hereditary muscle disorders, specifically focusing on myotubular myopathy (MTM) and glycogen storage disorder (GSD) type II. These are attractive diseases for gene therapy since they compromise a diverse family of rare genetic diseases typically caused by single gene defects that often provoke significant morbidity and mortality due to skeletal muscle, cardiac and/or diaphragm dysfunction. There are no effective cures and current treatment is suboptimal. MYOCURE focuses specifically on overcoming the key bottlenecks that hamper muscle-directed gene therapy by (i) boosting gene transfer using muscle-specific adeno-associated viral vectors (AAV) generated de novo by directed molecular evolution (ii) increasing expression by using robust computationally designed muscle-specific promoters that are 400-fold more efficient than the state of the art, allowing the use of lower and thus safer therapeutic vector doses (iii) minimize undesirable immune reactions against the vector, gene-modified muscle cells and therapeutic proteins. The efficacy and safety of this advanced therapy medical product (ATMP) will be validated in preclinical MTM and GSD II animal models. A scalable manufacturing process will be developed for subsequent toxicology studies and an orphan drug designation will be applied for. MYOCURE will consolidate a roadmap towards clinical development and economic valorisation and maximize dissemination to the relevant stakeholders. The outcome of MYOCURE will constitute the basis of a Phase I gene therapy clinical trial in MTM and GSD patients consistent with the IRDiRC objectives to provide 200 therapies for rare disease by 2020. MYOCURE applies to PHC14 New Therapies for Rare Diseases and advances the development of a new therapeutic option for patients suffering from these rare inherited muscle diseases, as well as related preclinical research and animal model development.
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: PHC-32-2014 | Award Amount: 3.66M | Year: 2015
Bioinformatic analysis is the biggest bottleneck in many genomic medicine projects. Our objective is to enable researchers to dramatically increase statistically informed use of personal multi-omic data in medicine. Soon, multiple types of omic technologies will be applied to 100,000s of patient-derived samples, with the three-stage goal of better understanding disease biology, discovery of new interventions, and personalizing the choice of treatment options. Our interdisciplinary team of biostatisticians, bioinformaticians, software developers and physician-scientists will address the analysis bottleneck with statistically and computationally sound methods. The SOUND consortium will (i) develop widely used and excellent bioinformatic and statistical methods and open source software for common but challenging tasks, including data pre-processing, data integration, statistical inference, visual presentation, and publication-quality reporting; (ii) introduce novel approaches to ground breaking multi-omics applications in oncology and medical genetics; (iii) develop interoperable data structures and software interfaces that enable seamless combination of tools; (iv) support a collaborative international academic and industry developer community; (v) enable rapid development and execution of high-quality software; (vi) lower the barrier to entry into this transdisciplinary field by providing simple, robust, easy-to-use solutions; and (vii) develop a training programme with regular courses and comprehensive online tutorials. Our aim is to create the de facto standard toolkit used in every clinical research lab for statistically informed analysis of personal multi-omic data. SOUND will increase research and innovation opportunities by reducing barriers of entry to genomic medicine across academic, healthcare and commercial sectors by translating in a rapid and efficient manner complex and innovative analytical approaches into modular, interoperable, reusable applications.