Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Treatment of NEonatal seizures with Medication Off-patent: evaluation of efficacy and safety of bumetanide (NEMO)

Framework: FP7 — Cooperation
Programme: Health
Destination: Other Actions across the Health Theme
Action type: Collaborative project
Countries involved: United Kingdom,Ireland,France,Finland,United Kingdom,Sweden,Germany,Netherlands,United States,Sweden,France,Netherlands
Call:  (FP7-HEALTH-2009-single-stage, 2009)
Start date: 2009-10-01
End date: 2015-03-31
Duration (months): 66.0
Total project cost (EUR): 7020774.08
EU funding (EUR): 5370802.64
Participants: 15
Project status: CLOSED

Neonatal hypoxic ischaemic encephalopathy (HIE) occurs in 2-3/1000 live births and is a major cause of both acute mortality and long-term neurodisability. Seizures are the hallmark of HIE. The clinical and electrographic seizure burden in babies with HIE can be considerable and is often not reduced by current antiepileptic drugs. Phenobarbitone remains the first line drug for neonatal seizures despite the fact that it has limited efficacy. Better treatments for neonatal seizures, particularly in asphyxiated babies, are a high research priority with the ultimate aim to improve long-term outcome. The aim of NEMO is to develop an effective treatment regimen for neonatal seizures using innovative strategies, targeted specifically to the needs and peculiarities of babies. An age dependent high expression of neuronal co-transporter resulting in excitatory rather than inhibitory function of GABA is believed to be responsible for the high incidence of seizures in the neonatal period. By blocking this co-transporter with bumetanide, a loop diuretic, the depolarizing action of GABA will be reversed resulting in reduced neuronal firing. Intensive EEG monitoring will enable us to accurately identify seizures and monitor treatment effect. A European-wide multicentre approach would, for the first time facilitate performing an RCT with enough statistical power in this age-group. By consolidating efforts from basic science, pharmacology and clinical centres we propose: 1. to perform a European-wide, multicentre, randomised, placebo-controlled, double-blind trial to evaluate the efficacy and safety of bumetanide in neonates 2. to perform pharmacokinetic and pharmacodynamic studies of bumetanide 3. to further investigate the mechanisms of action in non-clinical experiments 4. to develop and adapt a bumetanide formulation suitable for neonates in order to apply for a Paediatric Use Marketing Authorization (PUMA). 5. if results of the initial trial do not support a PUMA application we plan to apply for a Paediatric Investigation Plan (PIP) for lidoocaine to assess its efficacy as an AED for the control of seizures which are not controlled by phenobarbitone.

Keywords: neonatal seizures,drug development,bumetanide,off-patent,randomised controlled trial,pk/pd
Identification and therapeutic targeting of common arrhythmia trigger mechanisms (EUTRIGTREAT)

Framework: FP7 — Cooperation
Programme: Health
Destination: Translating research for human health
Action type: Collaborative project
Countries involved: Germany,Belgium,Italy,United Kingdom,Germany,Netherlands,Greece,Germany,France,United States,Switzerland,Germany
Call:  (FP7-HEALTH-2009-single-stage, 2009)
Start date: 2009-10-01
End date: 2015-03-31
Duration (months): 66.0
Total project cost (EUR): 16027880.4
EU funding (EUR): 12000000.0
Participants: 15
Project status: CLOSED

Arrhythmias are common manifestations of heart disease which frequently cause sudden cardiac death (SCD) or other devastating health problems. In Europe, prevention of SCD by device and drug therapy is expensive and increasingly strains public health resources due to a growing population at risk. However, identification of patients at increased risk for SCD is ineffective, and SCD prevention strategies are not directed at the underlying risk mechanisms. To address this challenging situation, new insights into genetic and environmental modulators of SCD risk, arrhythmia initiating mechanisms (Triggers) and therapeutic strategies (Treatments) are urgently needed. The EUTrigTreat consortium proposes a translational project strategy based on interactive objectives (modules). Module 1 investigates novel genetic arrhythmia mechanisms in patients and is supported by Module 2 which investigates genetic and environmental SCD risk modulators in animals with arrhythmias. Module 3 elucidates common environmental arrhythmia risk mediators including obesity and diabetes. Module 4 applies molecular and biophysical imaging techniques to identify novel risk biomarkers. Module 5 translates experimental data through computer modeling and prediction analysis. Modules 6 develops new SCD risk identification strategies through combined patient and experimental studies. Module 7 develops and validates novel therapeutic drug compounds and a new form of anti-arrhythmic device therapy. The pre-clinical and clinical activities will potentially result in patents of diagnostic and therapeutic applications, licensing strategies, early clinical trials and a spin-off company. Module 8 manages, advises and reviews the project progress of EUTrigTreat. Ultimately, we aim to better understand and educate about arrhythmia initiating mechanisms and associated risk biomarkers. Such knowledge will provide strong rationales towards improved prevention and treatment of patients at risk for SCD.

Keywords: arrhythmias,trigger mechanism,calcium,sodium,optical diagnostics,targeted therapeutics
Work Toghether to Stop Truancy Among Youth (WE-STAY)

Framework: FP7 — Cooperation
Programme: Health
Destination: Optimising the delivery of healthcare to European citizens
Action type: Collaborative project
Countries involved: Sweden,Estonia,France,Germany,Hungary,Israel,Italy,Romania,Slovenia,Spain
Call:  (FP7-HEALTH-2009-single-stage, 2009)
Start date: 2010-05-01
End date: 2013-04-30
Duration (months): 36.0
Total project cost (EUR): 3670569.6
EU funding (EUR): 2995947.0
Participants: 10
Project status: CLOSED

Truancy is a serious public health problem that affects adolescents from all countries around the world. In the United States, it has been reported that up to 35% of high school students skipped one or more days of school during a school year. However, little is known on the short- and long-term outcomes of underlying psychological and mental ill-health for those adolescents who truant. Research has indicated that truancy has severe and far reaching consequences, such as maladjustment, substance abuse, delinquency and crime. Most studies, performed in the USA, proposed mechanistic and law-enforcement interventions to prevent truancy. However this approach doesn’t take in consideration the psychological distress that is associated with this phenomenon and may even have negative consequences on adolescents’ well-being and mental health. The main objectives of the WE-STAY (Working in Europe to Stop Truancy among Youth) project are to gather epidemiological information on truancy on European adolescents; to perform intervention school-based programmes for adolescents, aimed at reducing truancy rates and improve mental health of students; to evaluate outcomes of the interventions, in comparison with a control group, from a multidisciplinary perspective including social, psychological and economical aspects; to recommend effective, culturally adjusted models for preventing truancy and promoting mental health of adolescents in different European countries. The WE-STAY project proposes to implement and evaluate outcomes of three different kinds of intervention against truancy: a) a universal intervention based on an awareness program for students, teachers and parents; b) a screening intervention aimed at identifying students at risk and refer them to mental health services; c) a combination of the above interventions. A mechanistic intervention to stop truancy will be used as control.

Keywords: adolescent child mental health promotion school-based transcultural truancy psychological distress risk factors screening prevention intervention lifestyles
Systems Biology of Mitosis (MITOSYS)

Framework: FP7 — Cooperation
Programme: Health
Destination: Translating research for human health
Action type: Collaborative project
Countries involved: Austria,Germany,United Kingdom,France,Germany,Italy,Switzerland,Spain,Netherlands,United Kingdom,Germany,United Kingdom
Call:  (FP7-HEALTH-2009-two-stage, 2009)
Start date: 2010-06-01
End date: 2015-05-31
Duration (months): 60.0
Total project cost (EUR): 15075776.04
EU funding (EUR): 10198241.0
Participants: 14
Project status: CLOSED

MitoSys will generate a comprehensive mathematical understanding of mitotic division in human cells, a process of fundamental importance for human health. To create the critical mass and multidisciplinarity that is needed to achieve this ambitious goal, internationally leading mathematicians, biochemists/biophysicists and biologists working at twelve universities, research institutes, international organizations and companies in eight different European countries will collaborate. Mathematicians will focus on four biological modules that represent the most important aspects of the mitotic cell division process; (i) spindle assembly, (ii) the spindle assembly checkpoint and kinetochores, (iii) segregation of mitotic chromosomes and (iv) mitotic exit. Computational models of these separate modules will be integrated into a comprehensive model of mitosis that combines these steps of mitosis with regulation by protein kinases and ubiquitin ligases. To be able to achieve these tasks, the modellers will be supported by biologists and physicists who will use microscopic imaging, biochemistry, biophysics, single-molecule techniques and proteomics to generate kinetic and other quantitative data suitable for model building. To evaluate the relevance of the mathematical models for human health and disease, other biologists will subject selected key predictions from these models to rigorous in-vivo tests by using conditional "knock-out" mice. MitoSys will compile and disseminate its own data and models, but also datasets from public sources, in a web-database, which will serve as a systems biology resource for the scientific community. To train other scientists in systems biology, MitoSys will organize a practical workshop on mathematical modelling. Finally, MitoSys will inform the general public about systems biology of mitosis and its relevance to health and disease by organizing an exhibition, which will be displayed in several European cities.

Keywords: human cell division,mitosis,mathematical modelling,quantitative biology,mouse genetics
Bench-to-beside Integrated approach to familial hypertrophic cardiomyopathy: to the HEART of the disease (BIG-HEART)

Framework: FP7 — Cooperation
Programme: Health
Destination: Translating research for human health
Action type: Collaborative project
Countries involved: United Kingdom,Netherlands,Italy,Germany,United Kingdom
Call:  (FP7-HEALTH-2009-single-stage, 2009)
Start date: 2010-01-01
End date: 2013-06-30
Duration (months): 42.0
Total project cost (EUR): 3768620.78
EU funding (EUR): 2912992.0
Participants: 7
Project status: CLOSED

Hypertrophic cardiomyopathy (HCM), characterised by left ventricular hypertrophy and myocyte disarray, is by far the most common cardiac single gene disorder. With a prevalence of 1:500, HCM is predicted to affect approximately one million people within the EU. HCM represents an important clinical problem, being the principal cause of sudden death in young adults, and a valuable opportunity to use human genetics to dissect mechanisms of cardiac hypertrophy and heart failure. It was the first inherited heart disease to be characterised at the molecular genetic level, with the demonstration that it is caused by mutations in genes that encode different components of the cardiac contractile apparatus. Existing in vitro and mouse model studies have suggested that HCM mutations enhance contractility and impair relaxation. We have hypothesised that these changes may result in energetic compromise, due to inefficient ATP utilisation, and also in altered Ca2+ handling. If validated in the human heart, these hypotheses would identify tractable therapeutic targets that suggest that HCM, perhaps more than any other cardiomyopathy, will be amenable to disease modifying therapy. However, analysis of the altered functional characteristics of affected human tissue has so far lagged behind the in vitro and mouse studies. In this project, we aim: (i) to collect and genotype a large collection of both affected HCM and appropriate control human myocardium and to measure the differences in protein expression, contractility, protein phosphorylation and sarcomeric structure between normal and affected samples; (ii) to test therapeutic strategies in our existing mouse models; (iii) to employ patient-based studies to test specific interventions based on existing hypotheses. This will provide a broad multidisciplinary approach to gain further understanding HCM and to yield new directions for therapeutic strategies.

Keywords: hypertrophic cardiomyopathy,contractility,myocytes,calcium,energetics,mouse models,genotype,cmr,pet
Systems biology of Mycobacterium tuberculosis (SYSTEMTB)

Framework: FP7 — Cooperation
Programme: Health
Destination: Translating research for human health
Action type: Collaborative project
Countries involved: Spain,Germany,United Kingdom,France,Switzerland,Poland,Czechia,Germany,Italy,Germany,Germany,Netherlands,Belgium
Call:  (FP7-HEALTH-2009-two-stage, 2009)
Start date: 2010-04-01
End date: 2014-09-30
Duration (months): 54.0
Total project cost (EUR): 13841311.87
EU funding (EUR): 10562601.0
Participants: 14
Project status: CLOSED

Tuberculosis (TB) is a re-emerging global health threat caused by Mycobacterium tuberculosis (Mtb). One third of the world&apos;s population is infected with Mtb and new infections occur at a rate of one per second. Despite global research efforts, mechanisms underlying pathogenesis, virulence and persistence of Mtb infection remain poorly understood. Simple reductionist approaches are insufficient to understand its complex biology. The grand goal of the SysteMTb project is to establish a Systems Biology framework to understand key features of Mtb and its interactions with the host which, in turn, will provide new insights and a solid (model based) knowledge for the development of novel and cost-effective strategies to combat tuberculosis. To achieve this, SysteMTb will: i) generate and integrate quantitative data sets of Mtb (e.g. transcriptomics, proteomics, metabolomics, structural genomics, lipidomics, glycomics) alone, or in the presence of host macrophages, ii) develop computer models at different appropriate levels of system complexity with emphasis on metabolism, regulatory networks and transcription regulation, and iii) identify new possible targets for therapeutic intervention based on computer modelling. The combination of these approaches will provide a rational framework to understand mycobacterial physiology during infection and to identify essential nodes that are optimal for effective therapeutic interventions.

Keywords: systems biology,mycobacterium,macrophages,omics,modelling
Therapeutic challenge in Leukodystrophies: Translational and ethical research towards clinical trials (LEUKOTREAT)

Framework: FP7 — Cooperation
Programme: Health
Destination: Translating research for human health
Action type: Collaborative project
Countries involved: France,Italy,Italy,Germany,France,United Kingdom,Spain,Germany,Austria,France,Netherlands,France,United Kingdom,Germany,Germany,Germany,Australia
Call:  (FP7-HEALTH-2009-single-stage, 2009)
Start date: 2010-03-01
End date: 2013-08-31
Duration (months): 42.0
Total project cost (EUR): 9249281.3
EU funding (EUR): 5978126.0
Participants: 25
Project status: CLOSED

Leukodystrophies (LDs) are inherited rare neurodegenerative diseases of the white matter and its main component, the myelin, that are affecting predominantly children. Severity of the disease is related to the axonal dysfunction due to myelin deficiency or destruction. Despite the achievement of remarkable advances made in the past decade, there is no current curative therapy. The development of therapeutic approaches for myelin repair and neuroprotection constitutes the main objective of the LeukoTreat project. Indeed LDs constitute prototypic pathologies to tackle myelin formation/destruction issues as well as glial cells dysfunctions in neurodegeneration. The global aim is to promote the development of therapeutic strategies for the largest number of LD affected patients and further applications to more common white matter disorders and finally neurodegenerative diseases. For this purpose, the project will combine the expertise of (i) recognized European research teams in the field of White Matter diseases (COST Myelinet), (ii) high-technology SMEs, (iii) experts in medical ethics and (iv) LD patients and families associations. To develop efficient therapies, the LeukoTreat project is based on 5 complementary approaches consisting in: (i) collecting information on the epidemiology, the natural history, the genotype/phenotype correlation of LDs for at least 500 patients; (ii) validating/identifying biomarkers for therapeutic decisions/follow up to isolate new therapeutic targets; (iii) developing pharmacological strategies with the ultimate objective to launch at least 4 pharmacological clinical trials during 5 years following the project; (iv) developing innovative gene and cell therapies with the ultimate objective to launch at least 3 clinical trials during the next 5 years; (v) tackling ethical impacts of the proposed therapeutic challenges by integrating the participation of patients driven by a well-experienced research team strongly skilled in ethics

Keywords: leukodystrophy,myelin,biomarkers,lipidomics,cellular stress,gene regulation,gene therapy,cell therapy
Fatty liver: Inhibition of Progression (FLIP)

Framework: FP7 — Cooperation
Programme: Health
Destination: Translating research for human health
Action type: Collaborative project
Countries involved: France,France,United Kingdom,United Kingdom,Italy,Italy,Austria,Switzerland,Spain,Denmark,Netherlands,Austria
Call:  (FP7-HEALTH-2009-single-stage, 2009)
Start date: 2010-01-01
End date: 2013-06-30
Duration (months): 42.0
Total project cost (EUR): 7808902.7
EU funding (EUR): 5983477.8
Participants: 17
Project status: CLOSED

Non-alcoholic fatty liver disease (NAFLD) has become one of the top concerns for the practising hepatogastroenterologist due to the obesity epidemic and its potential to progress to advanced liver disease which significantly impacts on overall and liver-related mortality. The aim of the FLIP (Fatty Liver: Inhibition of Progression) project is to understand and prevent the progression of liver disease in NAFLD. FLIP is a consortium of basic scientists and practising clinical hepatologists with an established track record and focus on research into the underlying mechanisms and management of patients with NAFLD. Therefore FLIP provides a unique opportunity to assemble the largest European cohort of patients with histologically diagnosed NAFLD with clinical and epidemiological data and with biobanks of DNA, frozen liver tissue and serum. These will be used in a wide range of collaborative inter-disciplinary research projects aimed at addressing key unanswered questions related to the mechanisms and consequences of liver injury in NAFLD and the development of novel preventive and therapeutic strategies. The main outcomes of FLIP will be new insights in the progression of liver disease in NAFLD in terms of initiating mechanisms and patients at risk, innovative diagnostic methods particularly adapted for large-scale screening and prognostic evaluation, improved implementation of lifestyle changes, collaboration with leading biotechnological or pharmaceutical companies in order to translate to the market diagnostic tests or newly identified molecular targets for pharmacological therapy. By disseminating the project’s results, FLIP will further help the European Community to suggest guidelines on the management of this emerging liver disease. The long-term goal is to lay the foundations for the future of NAFLD research in Europe by creating a Collaborative Research Network on NAFLD that will continue the work initiated by the FLIP consortium.

Keywords: nafld,non-alcoholic fatty liver disease,treatment,prevention,pathophysiology,diagnostic,non-invasive,markers,exercise,progression,fibrosis,hepatocellular cancer,kruppel-like factor 6,mcp-
Neuroscience on Barriers in Development (NEUROBID)

Framework: FP7 — Cooperation
Programme: Health
Destination: Translating research for human health
Action type: Collaborative project
Countries involved: Germany,France,Netherlands,United Kingdom,United Kingdom,Australia,Sweden,France,Germany,Austria
Call:  (FP7-HEALTH-2009-single-stage, 2009)
Start date: 2010-01-01
End date: 2013-12-31
Duration (months): 48.0
Total project cost (EUR): 4194375.47
EU funding (EUR): 2996324.0
Participants: 10
Project status: CLOSED

Brain diseases are one of the most prevalent groups of diseases in Europe with estimated annual costs amounting to €386 billion (1). Data collected by the WHO suggest that brain diseases are responsible for 35% of Europe’s total disease burden (1). In the treatment of neurological disease, the blood brain barrier (BBB) still represents an obstacle for the delivery of drugs to the brain and thus a major challenge for the development of therapeutic regimens. Understanding the molecular basis and functioning of the BBB in health and disease, including transport mechanisms across the BBB, therefore holds significant potential for future strategies to prevent and ameliorate neurological disease. Recent research indicates that some neurological disorders have a developmental etiologic component. The major goal of the NEUROBID project is thus to understand the molecular mechanisms and function of the BBB in health and disease both in the developing brain and the adult central nervous system. With an interdisciplinary consortium from the fields of developmental neurobiology and BBB research, NEUROBID aims to (i) understand the involvement of normal and disturbed BBB function in normal and abnormal brain development and (ii) to develop novel strategies for drug delivery to the brain. Unique transport mechanisms across the BBB will be used to target potential therapeutic macromolecular and cellular agents specifically to the brain barriers and transport them into the brain. The main target disorders of NEUROBID are non-inherited neurodevelopmental disorders arising from perinatal adverse exposure, such as cerebral palsy, and classic adult neurological disorders such as multiple sclerosis and stroke. In the long term, NEUROBID hopes to pave the way for new treatment strategies and thus reduce the economic and social burden of neurological disease. 1. Olesen J, et al. Consensus document on European brain research. J Neurol Neurosurg Psychiatry 2006;77 Suppl 1:i1-49.

Keywords: brain development,blood-brain barrier,developmental disorders,neurological disorders,neuropharmacology