Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
GSK-3 in neuronal plasticity and neurodegeneration: basic mechanisms and pre-clinical assessment. (NEURO.GSK3)

Framework: FP7 — Cooperation
Programme: Health
Destination: Translating research for human health
Action type: Collaborative project
Countries involved: Belgium,United Kingdom,Israel,Germany,Germany,Poland,Spain
Call:  (FP7-HEALTH-2007-B, 2007)
Start date: 2008-10-01
End date: 2011-12-31
Duration (months): 39.0
Total project cost (EUR): 5082027.48
EU funding (EUR): 3573842.0
Participants: 7
Project status: CLOSED

Neuronal circuits in mammalian brain act predominantly via excitatory synapses on dendritic spines. Formation of new spines in adult brain constitutes the structural basis of neuronal plasticity. The underlying molecular mechanisms remain largely unknown but depend essentially on kinase-dependent signalling pathways. Final formation of synapses on spines depends on dynamic interactions of microtubuli and actin-filaments that are also controlled by kinases. Deterioration of these processes to different extents are thought to cause the cognitive decline in normal ageing as well in Alzheimer&apos;s disease (AD) and familial fronto-temporal dementia (FTD). Protein tau is a microtubule associated protein and GSK-3 kinases are proposed as the major tau-kinases in vivo. Their exact contributions remain to be functionally defined in vivo both in normal neuronal plasticity and in degeneration. We develop pre-clinical models for AD and FTD that have tauopathy in common as essential pathogenic component and will explore the GSK-3 kinases in vivo by manipulating their activity genetically, pharmacologically and biochemically. Inhibitors are wanted that are effective and specific and enter brain in vivo. This proposal engages in three activities: (i) elucidate physiological functions of GSK-3 kinases in synaptic plasticity in adult and ageing brain, and in degenerating brain; define fundamental neuron-specific functions of GSK-3 kinases in vivo in novel mouse models; define contributions of GSK-3 kinases to amyloid and to tau pathology, separately and combined in vivo in validated mouse models (ii) design novel inhibitors of GSK-3 kinases and alternative tools to inhibit GSK-3 activity in vivo (iii) test pharmacological and peptidometic inhibitors of GSK-3 in validated mouse models of neurodegeneration for their restorative potential; analyse their mode of action and their acute and chronic effects by multi-parametric analysis

Keywords: gsk3 / spines / plasticity / alzheimer / tauopathy / kinase-inhibitors
Unraveling the molecular mechanism of nitrosative stress resistance in tuberculosis (NOSTRESS)

Framework: FP7 — Cooperation
Programme: Health
Destination: Translating research for human health
Action type: Collaborative project
Countries involved: Spain,India,Argentina,Spain,United Kingdom
Call:  (FP7-HEALTH-2007-B, 2007)
Start date: 2008-10-01
End date: 2012-03-31
Duration (months): 42.0
Total project cost (EUR): 1540956.4
EU funding (EUR): 1163264.0
Participants: 5
Project status: CLOSED

Tuberculosis is today amongst the major worldwide health threats. Treatment failure is unfortunately becoming more usual, especially in countries lacking the long and costly treatment adapted to patients. Thus, tuberculosis causes 2 million deaths every year and latently persists in over 1 billion individuals worldwide. Current treatments are challenged by multidrug resistant strains, drug side effects, and co-infections. Therefore, identification of potent, safety antimycobacterial agents is mandatory. However, the success of this strategy is largely determined by the detailed knowledge of their mechanism of action, which in turn depends on the validation of suitable biological targets. This project pursues the definition of new, complementary therapeutic approaches by identifying the molecular basis of the nitrosative stress resistance of M. tuberculosis. Our working hypothesis is that a decrease in the NO resistance of the microorganism should reduce significantly the capability to rest in latency, thus contributing to increase the efficacy of the therapeutic treatment. In this context, understanding of the NO detoxification activity played by M. tuberculosis trHbN is essential. Accordingly, our objectives are i) to unravel the molecular mechanism underlying the NO dioxygenase activity of M. tuberculosis trHbN, ii) to establish the structure-function relationships in trHbN and trHbO from M. tuberculosis, and iii) to identify the reductase protein system that helps trHbN to restore the ferrous state required to initiate the NO detoxification cycle. The outcome of the project should provide a firm basis to assess the viability of trHbN as a therapeutic target, and set up the background to exploit this knowledge in the design of innovative therapeutic strategies to fight the disease.

Keywords: nitric oxide,nitrosative stress,truncated hemoglobin,target validation
European Networks of Centres of Expertise for CF (Cystic Fibrosis), LAM (Lymphangioleiomyomatosis), and LTX (Lung Transplantation) (ENCE-CF-LAM-LTX)

Framework: FP7 — Cooperation
Programme: Health
Destination: Optimising the delivery of healthcare to European citizens
Action type: Coordination and support actions
Countries involved: Germany,United Kingdom,United Kingdom,France,Germany,Austria,France,Czechia
Call:  (FP7-HEALTH-2007-B, 2007)
Start date: 2009-04-01
End date: 2011-03-31
Duration (months): 24.0
Total project cost (EUR): 962242.0
EU funding (EUR): 857310.0
Participants: 8
Project status: CLOSED

European Centres of Expertise Networks for rare diseases have been identified by the European Commission as one important area of future activity in the attempt of achieving one of the main objectives across the EC endeavour of “Optimising the delivery of health care to European Citizens”. It is obvious that especially in rare diseases the joined forces of the experts networking throughout Europe are more likely than national services to meet the needs and expectations of patients. The construction and implementation of European networks of centres of expertise (ENCE) call for input from many different stakeholders: patients and doctors and other care team members, clinical researchers, health administration, and health insurers will have to be heard to come to a model of such networks that can easily be used as blueprint for most of the rare disorders. To achieve this goal first a mapping exercise of existing networks and elements needed for such networking has to be done. We plan to do so for three different rare entities, i.e. cystic fibrosis (CF), pulmonary lymphangioleiomyomatosis (LAM), and lung transplantation (LTX), having in common that they all comply with the EC definition of a rare disease. From the information gathered during this process the areas of activity and a detailed set of criteria for such European networks will be developed. These construction principles will be brought together in a blueprint to be used for other rare disorders. These criteria can then be used for certification, quality control, and funding of a European system of networks. Networking in this European sense will make the best possible use of resources already existing and remaining in the responsibility of the individual member states by interfacing and complementing these present and future elements. This will help the health care system partners to learn from the best and improve the quality of care to the best European level of expertise.

Keywords: rare disease,lam,cystic fibrosis,lung transplantation,centres of expertise networks,quality management,guidelines,access to information,cross border care,patient regitstry,clincal trials
Multi-layer network modules to identify markers for personalized medication in complex diseases (MULTIMOD)

Framework: FP7 — Cooperation
Programme: Health
Destination: Translating research for human health
Action type: Collaborative project
Countries involved: Sweden,United States,United Kingdom,Germany,Sweden,Norway
Call:  (FP7-HEALTH-2007-B, 2007)
Start date: 2008-11-01
End date: 2012-10-31
Duration (months): 48.0
Total project cost (EUR): 3644610.4
EU funding (EUR): 2525888.0
Participants: 6
Project status: CLOSED

The symptoms of complex disease like allergy, obesity and cancer depend on the products of multiple interacting genes. High-throughput techniques have implicated hundreds of genes. There are also considerable individual variations. A clinical implication of this may be inadequate treatment response, which is increasingly recognized as a cause of increased suffering and costs. Ideally, physicians should be able to routinely personalize medication based on a few diagnostic markers. Finding such markers is a formidable challenge. We hypothesize that translational clinical studies based on high-throughput genomics, advanced computing and systems biology may help to identify markers for personalized medication in complex diseases. We organize disease-associated genes in networks that are analyzed in a top-down manner. First, modules of interacting genes with distinct biological functions are identified. Then the modules are dissected to find pathways and finally upstream genes with key regulatory functions. We use bioinformatic methods that were recently described by us in Nature Genetics and Nature Biotechnology. An important focus of this project is to develop these methods to form multi-layer modules that integrate information about disease-associated changes on the DNA, RNA and protein levels. Since these levels interact, studies of the different levels can be interactively used to cross-validate the modules. This involves both genetic and experimental studies, but the ultimate test of the modules will be if they can be used for clinical predictions. For example, changes in RNA expression may be caused by a single nucleotide polymorphism (SNP) in a regulatory region. If so, the corresponding protein is tried as a marker to personalize medication. We have chosen hay fever as a model of complex disease because it is common, well-defined and readily examined in clinical and experimental studies. However, the methods may be generally applicable to complex diseases.

Keywords: microarrays,systems biology,allergic rhinitis,allergy
GENE THERAPY FOR INHERITED SEVERE PHOTORECEPTOR DISEASES (AAVEYE)

Framework: FP7 — Cooperation
Programme: Health
Destination: Biotechnology, generic tools and medical technologies for human health
Action type: Collaborative project
Countries involved: Italy,United Kingdom,Switzerland,Estonia
Call:  (FP7-HEALTH-2007-B, 2007)
Start date: 2008-11-01
End date: 2011-10-31
Duration (months): 36.0
Total project cost (EUR): 3907401.0
EU funding (EUR): 2971000.0
Participants: 4
Project status: CLOSED

The retina represents the visual sensory receptor of the nervous system (CNS). Inherited diseases like Retintitis Pigmentosa (RP) and Leber Congenital Amaurosis (LCA), for which no therapies are available, are due to mutations in genes preferentially expressed in the photoreceptor cells of the retina. Vectors derived from the adeno-associated virus (AAV) efficiently transduce the retina of animal models. AAV-mediated gene transfer reverts retinal pigment epithelium (RPE) defects and the safety of this strategy is being tested for the first time in humans by an AAVEYE partner. However, approaches to correct photoreceptor-specific diseases are inefficient. The objective of the AAVEYE consortium is to develop state-of-the art gene transfer to photoreceptors in the retina, and to provide pre-clinical proof-of-concept of gene therapy for severe blinding retinal photoreceptor diseases to be transferred from bench to bedside. AAVEYE, which uniquely combines leading European scientists in the fields of: AAV-mediated gene transfer to the retina, elucidation of the pathogenesis of photoreceptor degeneration and design of molecular diagnostics for inherited retinal diseases, will accomplish this through: 1) development of AAV-based long-term and safe gene transfer to photoreceptors through combinations of endogenous promoters and AAV serotypes. 2) assessment of the impact of AAV-mediated photoreceptor transduction on rescue of visual function in animal models of severe RP and LCA. 3) evaluation of the efficacy of combination of gene replacement with adjuvant molecules on photoreceptor survival. 4) characterization of patients with severe inherited photoreceptor diseases to move from bench to bedside the gene therapies strategies tested. The results of this proposal will provide the knowledge and validation to further develop novel AAV-mediated therapeutic approaches with a broad potential application in the retina and central nervous system.

Keywords: gene therapy,adeno-associated vectors,retinitis pigmentosa,leber congenital amaurosis,photoreceptors,physiological gene expression,gene replacement,combinatorial therapies,animal models,disea
Balkan Epidemiological Study on Child Abuse and Neglect (BECAN)

Framework: FP7 — Cooperation
Programme: Health
Destination: Optimising the delivery of healthcare to European citizens
Action type: Collaborative project
Countries involved: Bulgaria,Croatia,North Macedonia,Romania,Serbia,Bosnia and Herzegovina,Greece,Albania,Türkiye,Italy
Call:  (FP7-HEALTH-2007-B, 2007)
Start date: 2009-10-01
End date: 2013-01-31
Duration (months): 40.0
Total project cost (EUR): 2881858.11
EU funding (EUR): 2323346.0
Participants: 10
Project status: CLOSED

BECAN is an epidemiological study aiming at mapping child abuse and neglect (CAN) in the general population of 11 to 16-year-old children that attend and those that have dropped-out school and at identifying the number of reported/detected cases of CAN being recorded in at least 8 Balkan countries. Mapping of CAN will be achieved by applying two of the I-CAST questionnaires (ICAST-CH for children and ICAST_P for parents, created by ISPCAN with the support of UNICEF) to matched pairs of children and parents. I-CAST questionnaires will first be translated into the official languages of the participating countries and culturally validated. There is no information on the prevalence of CAN in the general population of children in Balkan countries, and this study is certainly the larger in sample size ever conducted in the Balkan area (over 30.000 children and parents), and probably one of the biggest globally. CAN is associated with unhealthy behaviour in children and adolescents. Particularly, due to the well established “circle of violence” phenomenon, domestic violence tends to reproduce itself. Preventive cutting off of that circle contributes substantially and more effectively in the disappearance of such unhealthy behaviour in both children and adults. It is also believed that this study will provide the basis for the harmonization of CAN screening procedures in the Balkan area, and offer valuable tools to relevant policy-making activities in all participating Balkan countries.

Keywords: healthy behaviour in children and adolescents,child abuse and neglect,screening,epidemiological study,i-cast questionnaires,parent-child paired samples
Safety and Appropriateness of Growth hormone treatments in Europe (SAGHE)

Framework: FP7 — Cooperation
Programme: Health
Destination: Optimising the delivery of healthcare to European citizens
Action type: Collaborative project
Countries involved: France,Belgium,Germany,Italy,Sweden,Switzerland,United Kingdom,Netherlands
Call:  (FP7-HEALTH-2007-B, 2007)
Start date: 2009-06-01
End date: 2012-11-30
Duration (months): 42.0
Total project cost (EUR): 3878026.8
EU funding (EUR): 2989154.0
Participants: 10
Project status: CLOSED

Recombinant growth hormone (GH) has been used since 1985. Current indications for GH use in children include GH deficiency and an increasing number of conditions where childhood short stature is not primarily due to deficient GH secretion. Approximately 40 000 children in the EU are treated with daily injections of GH. The efficacy of GH to increase adult height is undisputed in children with severe GH deficiency but is more limited in other indications where current estimates suggest a gain of about 1 cm of adult height per year of treatment. The clinical significance of height gains has been poorly evaluated. The possibility has been raised that GH use in childhood might increase the risk of cancer later in life. However, little data is available to further explore this concern. SAGhE is an integrated consortium of paediatric endocrinologist, epidemiologists and biostatisticians that will collect and analyse data to address the questions of appropriateness and safety of childhood GH treatments. The impact on both height and psychosocial components will be evaluated on a large unbiased metacohort of patients followed to adult height. Safety will be evaluated by analysing long term mortality and long term cancer incidence. The data obtained will then be integrated and disseminated to several levels of users. SAGhE will contribute to the aims of the FP7 Health work programme and to the new Community Action programme of public Health in the field of better use of medicines. It will realize the application of evidence-based medicine in Europe, by the size and design of the study, the independence and scientific quality of data analysis and its translation into evidence-based guidelines. It will be comprehensive at the EU level and will test for national differences. It will address patient safety, one of the key points of the work programme. SAGhE is unique worldwide in its design, size and potential to answer important questions raised on childhood GH treatments.

Keywords: growth hormone,short stature,psychosocial impact,safety,cancer risk
Enabling universal and equitable access to healthcare for vulnerable people in poor resource settings (EQUITABLE)

Framework: FP7 — Cooperation
Programme: Health
Destination: Optimising the delivery of healthcare to European citizens
Action type: Collaborative project
Countries involved: Ireland,Sudan,Malawi,South Africa,Norway,Namibia
Call:  (FP7-HEALTH-2007-B, 2007)
Start date: 2009-03-01
End date: 2013-02-28
Duration (months): 48.0
Total project cost (EUR): 3310605.46
EU funding (EUR): 2654943.0
Participants: 8
Project status: CLOSED

Healthcare can be neither universal nor equitable if it is less accessible to some sections of society than it is to others. EquitAble’s focus on activity limitations brings recent thinking on disability, public health and health policy together to provide data that is crucial to enable universal and equitable access to healthcare in resource poor settings. EquitAble is a four-year collaborative research programme comprised of both leading and upcoming researchers, from two European and four African countries. Each of the African partner countries represent distinct challenges in terms of equitable access to health care in contexts where a large proportion of the population has been displaced (Sudan); where the population is highly dispersed (Namibia); where chronic poverty and high disease burden compete for meagre resources (Malawi); and where, despite relative wealth, universal and equitable access to health care is yet to be attained (South Africa). Documentary analysis of international and country-level health policy will identify health policy aspirations and challenges; along with opportunities for alignment and harmonisation, between different stakeholders. Intensive qualitative interviews and case studies, along with behavioural observations will explore the experiences of healthcare users, non-users and providers, and feed into the development of a household survey instrument. The extensive quantitative household survey will allow us to test models of access to healthcare, taking into account how the relationship between activity limitations and healthcare access is mediated by, or interacts with, cultural, contextual and systems variables. These work packages will constitute a much needed evidence base for health policy and practice in resource poor areas. EquitAble also goes beyond the provision of information and addresses how to ensure that research evidence affects policy and practice; both within the EU and Africa.

Keywords: universal access,vulnerable people
Understanding and combating human age-related muscle weakness (MYOAGE)

Framework: FP7 — Cooperation
Programme: Health
Destination: Translating research for human health
Action type: Collaborative project
Countries involved: France,Italy,Denmark,United Kingdom,Italy,Netherlands,Belgium,Spain,Estonia,Finland,Sweden
Call:  (FP7-HEALTH-2007-B, 2007)
Start date: 2009-01-01
End date: 2013-06-30
Duration (months): 54.0
Total project cost (EUR): 14991949.0
EU funding (EUR): 11200000.0
Participants: 18
Project status: CLOSED

Ageing of skeletal muscle results in a progressive loss of mobility that decreases the quality of life and has major economic and social consequences for society at large. Increasing muscle weakness is a major component of muscle ageing. In the elderly muscles become atrophic (loss in muscle mass) and weaker (loss in muscle force), more susceptible to damage and consequently regenerate and recover more slowly than was the case in their youth. The challenge for FP7 is to identify the relative importance of sarcopaenia, thus proposing standards to define healthy ageing in order to identify age-related muscle weakness; secondly to identify molecular pathways which may be targeted to combat normal age related muscle weakness, and thirdly to identify therapeutic strategies to prevent muscle loss and weakness and enhance recovery following injury or immobilisation. The approaches which we will take to understand and combat muscle weakness in the aged population and improve healthspan can be defined in several steps: the collection and collation of data and samples, the assessment of physiological and functional parameters, the understanding of the various biological mechanisms involved, leading through integration to the development of strategies and their translation for the general European population. In order to develop and propose the general public with efficient countermeasures, the consortium will integrate data from genetics and epidemiology, molecular and cellular biology, physiology, biomechanics, as well as clinical and public health aspects, to ensure optimal scientific synergy from the leading European specialists and companies.

Keywords: human muscle,loss in mobility,atrophy,recovery,exercise,diet,signaling,protein turnover,oxydative stress