Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
LSE TECHNOLOGY APPROACH TO GENERATE INNOVATIVE KINASE INHIBITOR DRUGS (LSE)

Framework: FP7 — Cooperation
Programme: Health
Destination: Translating research for human health
Action type: Collaborative project
Countries involved: Netherlands,United Kingdom,Netherlands,Italy,Italy,United Kingdom
Call:  (FP7-HEALTH-2012-INNOVATION-1, 2012)
Start date: 2013-02-01
End date: 2015-07-31
Duration (months): 30.0
Total project cost (EUR): 1883305.12
EU funding (EUR): 1449681.0
Participants: 6
Project status: CLOSED

Over the last decade, kinases have emerged as attractive therapeutic targets in inflammatory diseases. Numerous efforts in the pharmaceutical community are directed towards the discovery of small molecule inhibitors that regulate kinase function. A number of issues need to be addressed when considering kinases as targets in inflammation. The combination of efficacy and favourable safety profile is often key for the successful treatment of chronic inflammatory and/or autoimmune diseases with kinase inhibitors. The LSE (Low Systemic Exposure) approach is a Creabilis proprietary technology that generates innovative molecules with unique physico-chemical and pharmacological characteristics. LSE molecules are ‘topical by design’ molecules that share some common features. They combine high local concentration with poor systemic absorption and distribution. If absorbed, LSE molecules are rapidly eliminated from the systemic circulation (very short plasma half-life), thus generating no/low side effects. LSE approach has already been clinically validated through CT327, a selective topical kinase inhibitor that recently reported positive Phase 2a data in both psoriasis and atopic dermatitis. This project will combine Creabilis experience and know-how on LSE modification of molecules with the sound systems biology and network pharmacology expertise of the University of Dundee to generate and bring to preclinical development a new generation of innovative molecules optimised for topical treatment of inflammatory diseases, such as psoriasis, atopic dermatitis and inflammatory bowel disease. The generated lead compound(s) will be characterized by minimal or no systemic toxicity combined with efficacy and optimised selectivity. This would tremendously widen the range of patients affected by inflammatory pathologies that could benefit of topical kinase inhibition as a therapy and provide an innovative concept for new medicines to be developed.

Keywords: kinase function inhibitor inflammatory disease low systemic exposure selective topical psoriasis atopic dermatitis inflammatory bowel disease
A Multi-Stage Malaria Vaccine (MULTIMALVAX)

Framework: FP7 — Cooperation
Programme: Health
Destination: Translating research for human health
Action type: Collaborative project
Countries involved: United Kingdom,France,Italy,Italy,Germany
Call:  (FP7-HEALTH-2012-INNOVATION-1, 2012)
Start date: 2012-10-01
End date: 2017-03-31
Duration (months): 54.0
Total project cost (EUR): 8055788.47
EU funding (EUR): 6000000.0
Participants: 6
Project status: CLOSED

A highly effective malaria vaccine is a major goal of global health research and will likely require a multi-stage product. MultiMalVax will develop a highly effective multi-stage malaria vaccine to the point of proof-of-concept phase II testing in Europe, prior to trials in malaria-endemic areas. Remarkable recent advances in vaccine design for all four stages of the P. falciparum parasite’s life-cycle allow testing of a multi-stage multi-component vaccine for the first time, with strong chances of success. These advances are i) the availability of a new vectored prime-boost vaccination regime based on the ReiThera Srl's chimpanzee adenovirus technology that has been found to induce exceptionally potent CD8+ T cell responses and high titre antibodies against multiple malaria antigens; ii) the development of an improved version of the leading partially protective RTS,S sporozoite vaccine candidate, termed R21, that lacks the excess of HBsAg in RTS,S; iii) the identification, using a vector technology screen, of the blood-stage antigen RH5 as the first antigen to induce potent strain-transcending neutralisation of blood-stage parasites in in vitro growth inhibition assays; and iv) the demonstration that vector-induced antibodies against two mosquito-stage antigens can induce 100% transmission blocking against field isolates of P. falciparum in Africa. We will undertake four phase I / II clinical trials to assess the pre-erythrocytic, blood-stage and mosquito-stage components individually, and then together, using state-of-the art immunomonitoring, key functional assays of vaccine-induced immunogenicity, and sporozoite and blood-stage parasite challenges to measure efficacy prior to field testing. This SME-led collaboration of a leading SME, two universities, the major European product development partnership for malaria vaccines, and a global pharmaceutical company will provide complementary abilities to accelerate development of this promising product.

Keywords: parasite,vaccine,efficacy,immunogenicity,safety,vectors,multi-component,virus-like particle,transmission-blocking,t cell-inducing,global health,microbial challenge study,pdp
SYSTEMS BIOLOGY OF PATHWAYS INVOLVING BRAIN AGEING (AGEDBRAINSYSBIO)

Framework: FP7 — Cooperation
Programme: Health
Destination: Translating research for human health
Action type: Collaborative project
Countries involved: France,Belgium,France,France,Germany,Israel,Estonia,Germany,Switzerland,United Kingdom,Germany,Belgium
Call:  (FP7-HEALTH-2012-INNOVATION-1, 2012)
Start date: 2013-01-01
End date: 2017-06-30
Duration (months): 54.0
Total project cost (EUR): 8228461.4
EU funding (EUR): 6000000.0
Participants: 15
Project status: CLOSED

In spite of valuable approaches applied to get a broad understanding of genetic, epidemiologic and molecular and system-level biological principles of human aging, cognitive decline remains as one of the greatest health challenges of the old age, with nearly 50% of adults over 85 afflicted of Alzheimer’s disease. Furthermore, drug development has not performed as expected in clinical trials, at least in part because of an insufficient mechanistic understanding at the systemic level in human. AgedBrainSYSBIO is a timely and straightforward project based on the integration of available transcriptomics, proteomics and metabolomics data, addition of relevant novel sets of data, their modeling and experimental testing in both human, mouse and drosophila. The concept is to identify subsets of pathways with two unique druggable hallmarks: (i) the validation of interactions occurring locally in subregions of neurons and (ii) a human and/or primate accelerated evolutionary signature, using six interacting approaches: (1) the identification of interacting protein networks from recent Late-Onset Alzheimer Disease- Genome Wide Association Studies (LOAD-GWAS) data, (2) the experimental validation of interconnected networks working in subregion of a neuron (such as dendrites and dendritic spines), (3) the inclusion of these experimentally validated networks in larger networks obtained from available databases to extend possible protein interactions, (4) the identification of human and/or primate positive selection either in coding or in regulatory gene sequences,(5) the manipulation of these human and/or primate accelerated evolutionary interacting proteins in human neurons derived from induced Pluripotent Stem Cells (iPSCs) and modeling prediction challenged in drosophila and novel mouse transgenic models. This work will finally allow (6) the validation of new druggable targets and markers as a proof-of-concept towards the prevention and cure of aging cognitive defects.

Keywords: systems biology,systems medicine,aging,synapses,proteins,existing data,mouse models,human induced pluripotent stem cells,druggable targets,systems
Clinical European study on the outcome of surgical and hormonal therapy and psychological intervention in disorders of sex development (DSD) (DSD-LIFE)

Framework: FP7 — Cooperation
Programme: Health
Destination: Translating research for human health
Action type: Collaborative project
Countries involved: Germany,Germany,Germany,Netherlands,Netherlands,United Kingdom,France,France,France,Germany,Sweden,Poland,Germany,Poland,France
Call:  (FP7-HEALTH-2012-INNOVATION-1, 2012)
Start date: 2012-10-01
End date: 2017-03-31
Duration (months): 54.0
Total project cost (EUR): 3878707.62
EU funding (EUR): 2999956.0
Participants: 18
Project status: CLOSED

Disorders of sex development (DSD) are a conglomerate of rare diseases with an estimated incidence of 1: 4500. The causes of DSD are mainly disorders with gonadal dysgenesis, decreased androgen synthesis or function in XY males or disorders with elevated androgen production in XX females. Decision on sex of rearing is difficult in some cases as the prenatal androgen imbalances result in ambiguous genitalia at birth and furthermore they are likely to influence psychosexual development. Genital constructive surgery is needed in most cases. Lifelong cortisone replacement is needed in DSD due to defects of cortisone synthesis. Sex hormone substitution is indicated in many cases of DSD in puberty and adult life. Decision of sex of rearing, genital surgery and hormone therapies have a life-long impact on the affected individuals, which become evident mainly after puberty. In many cases psychological counselling is advised. Interpretation of previous outcome studies of DSD is hampered by small patient numbers and conglomerates of diagnoses and therapies. The study DSD-Life investigates and compares the long-term outcome of different off-label treatments in adequate numbers of adolescents and adults with different known genetic entities of DSD to develop recommendations for treatment of DSD. To reach this aim, the influences and interrelations of sex assignment, genital surgery, hormone therapy, metabolism, fertility, psychological intervention but also cultural influences and patients’ and parents’ views on psychosocial adaption, health related quality of life and psychological well-being and will be investigated. The long-term impact of the study will be improvement of care and subsequently higher quality of life with better integration and participation of individuals with DSD in the society.

Keywords: disorders of sex development,dsd,endocrinology,genital surgery,psychosexual development,health related quality of life
Ultra-low dose of IL-2 for the treatment of recently diagnosed type 1 diabetes (DIABIL-2)

Framework: FP7 — Cooperation
Programme: Health
Destination: Translating research for human health
Action type: Collaborative project
Countries involved: France,United Kingdom,Switzerland,Germany
Call:  (FP7-HEALTH-2012-INNOVATION-1, 2012)
Start date: 2012-10-01
End date: 2019-03-31
Duration (months): 78.0
Total project cost (EUR): 7603061.98
EU funding (EUR): 5900000.0
Participants: 7
Project status: CLOSED

Concept The discovery of regulatory T cells (Tregs) has revolutionized our understanding of autoimmune diseases. As T1D is caused by the failure of Tregs to block autoimmune destruction of pancreatic ß-cells, Treg stimulation has the potential to stop the process, preserve ß-cells’ insulin secretion, and likewise prevent or delay disease progression and improve clinical outcome for patients. Background Low-dose interleukin-2 (ld-IL2) was recently shown to stimulate Tregs without stimulating effector T cells. In NOD mice, ld-IL2 can prevent and cure T1D. In humans, (i) we showed that ld-IL2 is safe, induces Tregs and is associated with clinical improvement in patients with autoimmune vasculitis; and (ii) we performed a dose-finding study in T1D to define an ultra-low dose IL-2 (uld-IL2) that is well tolerated and induces Tregs’ numbers and functionality. With this strong background – a well defined mechanism of action; proof of concept in NOD mice; proof of principle in a clinical trial with another autoimmune disease; safety and activity/efficacy data in T1D – we propose a phase-II clinical trial testing the efficacy of uld-IL2 for preserving ß-cells. Method This will be a double-blind randomised placebo-controlled, age-stratified (6-35 year), multicentre European trial assessing efficacy and safety of uld-IL2 (0.5M IU/m2/day with a maximum of 1 MIU/m2/day for adult patients) in 138 recently-diagnosed T1D patients. Our methodology strictly follows the Immunology of Diabetes Society consensus recommendations and European regulatory guidelines. The primary end-point is the change from baseline of AUC C-peptide during a mixed meal test at 1 year. The trial is precisely and conservatively powered to detect an effect size of d=0.5. Impacts If successful, this trial will have profound impacts for the management of patients with recently-diagnosed T1D, their families and EU economy. It will be a milestone towards preventing T1D in people at risk of this increasingly common childhood disease.
A novel drug discovery method based on systems biology: combination therapy and biomarkers for Multiple Sclerosis (COMBIMS)

Framework: FP7 — Cooperation
Programme: Health
Destination: Translating research for human health
Action type: Collaborative project
Countries involved: Spain,Switzerland,Sweden,Germany,Germany,Greece
Call:  (FP7-HEALTH-2012-INNOVATION-1, 2012)
Start date: 2013-01-01
End date: 2014-12-31
Duration (months): 24.0
Total project cost (EUR): 3273834.4
EU funding (EUR): 2509680.0
Participants: 8
Project status: CLOSED

The therapeutic challenge of complex diseases requires the use of combination therapies to target the distinct mechanisms and pathways involved. Such complex diseases will benefit from the design of computational models adopting a systems perspective to integrate the knowledge generated by ‘omics technologies and clinical data. Multiple Sclerosis is a prototypic debilitating complex disease in which an autoimmune attack is launched against the brain. Current therapies for MS are far from effective and target only part of the immune response. Hence, the need to develop combination therapies with good safety profiles that better control this condition, the main aim of CombMS. By understanding how current MS therapies work in biological networks and taking advantage of novel compounds, more effective combination therapies will be designed for MS. Indeed, the tools developed will be applicable to other immune and complex diseases to improve their therapeutic options in the future. The data for the modelling process will be generated from biological and clinical samples, and the predictions about combination therapies from the computational models tested using in vitro and animal models of MS. Given the limitations of animal models in translational research, we shall focus on studying the phosphoproteome in samples from individuals with MS (PBMC) using xMAP technology. The phosphoproteome has been identified as a system likely to be affected in MS and the novel therapeutic compounds that will be tested are known to act through signalling pathways involving receptor tyrosine kinases. The mechanistic modelling will be extended to the different levels of the response to therapy by analysing biological networks integrating gene and protein networks, with drugs, their effects and side-effects. As well as developing new combination therapies for MS, CombMS will provide proof of concept of the useful short term results that a systems biology drug discovery approach can provide.

Keywords: systems biology,multiple sclerosis,drug discovery,combination therapy,drug repositioning,signalling networks,autoimmune diseases,neuroprotection
Advanced coupling of low order combustor simulations with thermoacoustic modelling and controller design (ACOULOMODE)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Starting grants
Action type: Support for frontier research (ERC)
Panel: Products and process engineering
Countries involved: United Kingdom
Call:  (ERC-2012-StG_20111012, 2012)
Start date: 2013-01-01
End date: 2017-12-31
Duration (months): 60.0
Total project cost (EUR): 1489309.0
EU funding (EUR): 1489309.0
Participants: 1
Project status: CLOSED

Combustion is essential to the world’s energy generation and transport needs, and will remain so for the foreseeable future. Mitigating its impact on the climate and human health, by reducing its associated emissions, is thus a priority. One significant challenge for gas-turbine combustion is combustion instability, which is currently inhibiting reductions in NOx emissions (these damage human health via a deterioration in air quality). Combustion instability is caused by a two-way coupling between unsteady combustion and acoustic waves - the large pressure oscillations that result can cause substantial mechanical damage. Currently, the lack of fast, accurate modelling tools for combustion instability, and the lack of reliable ways of suppressing it are severely hindering reductions in NOx emissions. This proposal aims to make step improvements in both fast, accurate modelling of combustion instability, and in developing reliable active control strategies for its suppression. It will achieve this by coupling low order combustor models (these are fast, simplified models for simulating combustion instability) with advances in analytical modelling, CFD simulation, reduced order modelling and control theory tools. In particular: * important advances in accurately incorporating the effect of entropy waves (temperature variations resulting from unsteady combustion) and non-linear flame models will be made; * new active control strategies for achieving reliable suppression of combustion instability, including from within limit cycle oscillations, will be developed; * an open-source low order combustor modelling tool will be developed and widely disseminated, opening access to researchers worldwide and improving communications between the fields of thermoacoustics and control theory. Thus the proposal aims to use analytical and computational methods to contribute to achieving low NOx gas-turbine combustion, without the penalty of damaging combustion instability.

Keywords: combustion instability,gas turbines,thermoacoustics,feedback control
Systems prediction of Chronic Lung Allograft Dysfunction (SYSCLAD)

Framework: FP7 — Cooperation
Programme: Health
Destination: Translating research for human health
Action type: Collaborative project
Countries involved: Switzerland,France,France,France,Germany,Germany,France
Call:  (FP7-HEALTH-2012-INNOVATION-1, 2012)
Start date: 2012-11-01
End date: 2014-10-31
Duration (months): 24.0
Total project cost (EUR): 3932547.1
EU funding (EUR): 2999152.0
Participants: 9
Project status: CLOSED

Lung transplantation (LT) is the standard of care for selected patients with chronic respiratory failure. Chronic lung allograft dysfunction (CLAD) (i.e. “Bronchiolitis obliterans syndrome” (BOS) and “Restrictive Allograft Syndrome” (RAS)) represents a major health risk for LT recipients, requiring the use of heavy treatments and possible retransplantation. Observed in almost 50% of patients after 5 years post LT, it is currently impossible to predict the appearance of CLAD before the onset of first symptoms. This project aims to develop the SysCLAD model which will allow to predict, within the 1st year post LT, the recipients at risk of developing CLAD by 3 years post LT. Building upon available data from the cohort of lung transplantation (COLT, recruited since mid-2009), this project will integrate new LT recipients to form the European cohort of lung transplantation (ECOLT). The SysCLAD prediction tool will be based on a mathematical model developed through a system biology approach integrating both clinical and biological data collected from a total of 400 LT recipients. The model will be validated on the first 200 LT recipients (3 years follow-up at project start) and refined using the new set of 200 LT data with 3 years follow-up by 2014. The aim is to identify and validate the signature of CLAD both at the clinical and molecular levels to allow for an early recognition and specific interventions in patients at risk of CLAD. The implementation of the model is expected to significantly improve the cost-effectiveness of post-LT treatments, limit the risk of graft rejection in LT recipients and, ultimately lead to an improved quality of life and a prolonged life expectancy of patients following LT. Finally, the SysCLAD model holds further great promises in the context of other chronic bronchial inflammatory diseases of major incidence such as severe asthma and Chronic Obstructive Pulmonary Disease (COPD) to predict decline in lung function.

Keywords: lung transplantation,chronic lung allograft dysfunction,bronchiolitis obliterans syndrome,restrictive allograft syndrome,systems biology,omics,prediction
Health Care Reform: the iMpact on practice, oUtcomes and costs of New roles for health pROfeSsionals (MUNROS)

Framework: FP7 — Cooperation
Programme: Health
Destination: Optimising the delivery of healthcare to European citizens
Action type: Collaborative project
Countries involved: United Kingdom,Germany,Netherlands,Italy,Czechia,United Kingdom,Poland,Türkiye,Norway
Call:  (FP7-HEALTH-2012-INNOVATION-1, 2012)
Start date: 2012-10-01
End date: 2017-03-31
Duration (months): 54.0
Total project cost (EUR): 3764949.2
EU funding (EUR): 2999660.25
Participants: 9
Project status: CLOSED

The proposed research responds to the call for research into the ‘Quality, Efficiency and Solidarity of Health Systems’. European countries are reforming their health systems to improve health care delivery. One of the ways they are doing this is by changing skill mix within teams delivering health services: extending the roles of existing health professions and introducing new ones. This project will undertake a systematic evaluation of the impact of these ‘new professional roles’ on practice, outcomes and costs in a range of different health care settings within European Union and Associate Countries. It will detail the nature, scope and contribution of the new professional roles, evaluate their impact on clinical practice and outcomes, and identify their scope to improve the integration of care. It will conduct economic evaluation to identify the cost effectiveness of the new professional roles, identify optimal models for delivery of health care and the consequences of these for management of human resources and workforce planning. Study design is cross-sectional and multi-level. A mixed methods approach will combine analysis of routinely collected data and primary data generated through interviews and questionnaires to health professionals, managers and patients. Data analysis will employ multi-level modelling techniques.

Keywords: skill mix,new professional roles in health care,care pathways,the integration of care,cost effectiveness,optimal models for service delivery,workforce planning,management of human resources.