Data-Gouv-ML/pcri-informations-sur-les-projets-laureats huggingface dataset:
Mimicking pathogens; an integrated nano-medicine approach to developing intelligent cancer vaccines. (PATHFINDER)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Diagnostic tools, therapies and public health
Countries involved: Netherlands
Call:  (ERC-2010-AdG_20100317, 2010)
Start date: 2011-11-01
End date: 2017-10-31
Duration (months): 72.0
Total project cost (EUR): 2498680.0
EU funding (EUR): 2498680.0
Participants: 1
Project status: CLOSED

Tumour cells survive and grow because they are not effectively recognized by the immune system as ¿foreign¿ and are therefore not attacked and destroyed like most pathogens. We have already demonstrated the clinical value of dendritic cell (DC) vaccines that activate the immune system to fight cancer. Treating more than 300 patients with metastatic melanoma, we achieved extended survival in 40% of patients by maturing dendritic cells from the patient¿s blood in-vitro, loading them with cancer-specific antigens and re-injecting them into the patient. These DCs then activate tumour-specific T cells in the lymph nodes. Our success in this area of research makes us a world leader in dendritic cell immunotherapy. However, despite these encouraging results, more work needs to be done if this type of therapy is to move into routine cancer care. Therefore the primary objective of the research detailed in this proposal is to significantly enhance cancer treatment efficacy by developing multifunctional nano-sized vaccine carriers that specifically target DCs and T cells in-vivo. If successful, this will also eliminate the costly in-vitro steps associated with current dendritic cell therapy. The recent discovery of pathogen recognition receptors on dendritic cells opens up the possibility of exploiting these receptors to target dendritic cells within the body. We will therefore develop highly functionalized, slow-release vaccine carriers that target DCs in this way. In order to directly activate tumour-specific T cells, we will develop highly flexible polyisocyanide polymers that mimic naturally occurring DCs. To functionalize these polymers, we aim to develop a revolutionary DNA-based bar-coding technique. I expect this new approach leads to major advances in tumour immunotherapy.

Keywords: immuno therapy,nano-medicine,in-vivo targeting,imaging,chemical biology,vaccine carrier
Cell and gene therapy approaches for inherited diseases with unsatisfying or no therapeutic option (REGENERATIVETHERAPY)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Diagnostic tools, therapies and public health
Countries involved: France
Call:  (ERC-2010-AdG_20100317, 2010)
Start date: 2011-10-01
End date: 2016-09-30
Duration (months): 60.0
Total project cost (EUR): 2397215.0
EU funding (EUR): 2397215.0
Participants: 1
Project status: CLOSED

We have developed the tools and experimental models and have provided the proof of principle that gene modified autologous haematopoietic stem cells can restore a complete immunological system in vivo in a particular form of SCID. We are pursuing these efforts applying this strategy to several other diseases : two lentivirus protocols for X-linked adrenoleukodystrophy, Thalassemia and sickle cell disease, are developed in our Clinical Investigation Centre. In 2010, we plan to initiate two other gene therapy trials for two primary immunodeficiencies (SCID-X1 and Wiskott-Aldrich syndrome). Our expertise in translational medicine has now been used to transfer into clinics a new gene therapy protocol for a devastating inherited skin disease : dystrophic epidermolysis bullosa. To complement these approaches, we optimize HLA-mismatched haematopoietic stem cell transplantation (HSCT). They are an important therapeutic option for children with primary immunodeficiencies but the delayed reconstitution of the T-cell compartment following T-cell depleted HSCT remains a major clinical concern thus drastically limiting its broader clinical application. In order to speed-up the immunological reconstitution in this setting, we try to pre-clinically develop a new approach able to generate a large quantity of T-cellular precursors from a fraction of the donor CD34+ stem cells shortly cultured on Notch delta 4 ligand. This strategy could ideally provide the recipient with a pool of diverse T-cells within the first month after transplantation conferring T-cellular immunity before de novo thymopoiesis takes place. The results obtained with this procedure are so important that we think to extend its use to the transduction of HSC for the gene therapy trials.

Keywords: cell therapy - gene therapy - inherited diseases
General and targeted approaches to unravel the molecular causes of type 2 diabetes (GENE TARGET T2D)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Physiology, Pathophysiology and Endocrinology
Countries involved: Sweden
Call:  (ERC-2010-AdG_20100317, 2010)
Start date: 2011-05-01
End date: 2016-04-30
Duration (months): 60.0
Total project cost (EUR): 2499479.6
EU funding (EUR): 2499479.6
Participants: 1
Project status: CLOSED

Type 2 diabetes (T2D) affects worldwide at present about 250 million patients and an estimated 380 million in 2025. This epidemic has been ascribed to a collision between genes and an affluent society. Genetics of T2D has during recent years identified > 30 variants increasing susceptibility to T2D. Yet, these variants explain only 15% of the heritability of T2D. One reason could be that whole genome association studies can only detect common variants whereas identification of rare variants with stronger effects would require sequencing. A large part of this application is devoted to sequencing of affected family members from unique large pedigrees traced back to common ancestors around 1600. The advantage of using families is that identified variants can be tested for segregation with the trait. Genetic variants can influence expression of a gene in an allele specific manner. This will be explored by combining exome sequencing with sequencing of RNA from human islets. Impaired effects of the incretin hormones GLP-1 and GIP on the pancreatic islets represent central defects in T2D. Variants in the TCF7L2 and GIPR genes contribute to these defects. I will here explore the molecular mechanisms by which TCF7L2, the strongest T2D gene, causes T2D. GIP has unprecedented effects not only on islet function but also on body composition, blood flow and vascular complications in T2D. This application explores these effects and will test whether manipulation of GIP can mimic the normalization of glucose tolerance seen after gastric bypass surgery. Taken together, these general and targeted approaches are expected not only to provide new insights into the causes of T2D but also contribute with vital information for development of new treatments for T2D.

Keywords: tcf7l2,gip(r),gwas,exome,rnasequencing,bariatric surgery,osteopontin,gaba,novel therapy
The Plant Immune System: a multidisciplinary approach to uncover how plants simultaneously deal with beneficial and parasitic organisms to maximize profits and protection (PLANTIMMUSYS)

Framework: FP7 — Ideas
Programme: European Research Council
Theme: European research council
Destination: Advanced grants
Action type: Support for frontier research (ERC)
Panel: Applied life sciences and biotechnology
Countries involved: Netherlands
Call:  (ERC-2010-AdG_20100317, 2010)
Start date: 2011-03-01
End date: 2017-02-28
Duration (months): 72.0
Total project cost (EUR): 2500000.0
EU funding (EUR): 2500000.0
Participants: 1
Project status: CLOSED

In nature, plants live in complex environments in which they are attacked by a multitude of pathogens and pests. In agriculture this leads to tremendous annual crop losses, representing a value of over 450 billion worldwide. Beneficial associations between plants and other organisms are abundant in nature as well, improving plant growth or aiding plants to overcome biotic or abiotic stress. In the past years, we pioneered research on the complexity of the natural plant immune system that is engaged in interactions of plants with beneficial microbes, pathogens and insect herbivores. We discovered that the plant immune signaling network finely balances the plant¿s response to beneficial and harmful organisms to maximize both profitable and protective functions. As plants have co-evolved with an enormous variety of alien organisms, they harbour a fantastic reservoir of natural defensive mechanisms that until to date remained largely untapped. Here, I propose to mine this undiscovered natural resource in detail, using the Arabidopsis thaliana model system, and an innovative multidisciplinary approach involving a unique combination of state-of-the-art microbial and plant functional genomics, ecogenomics, molecular genetics, cellular biology, computational biology and bioinformatics. The outcomes of the proposed project will provide a detailed understanding of the intrinsic capacity of the plant immune system to simultaneously accommodate mutualists and ward off enemies in order to maximize benefits and minimize damage. Profitably, the discovery of novel plant loci and mechanisms involved in plant immunity will provide multi-faceted possibilities for development of new strategies for sustainable agriculture and resistance breeding of economically relevant crop species.

Keywords: plant immune system,plant-multi species interactions,beneficial microbial communities,plant defense signaling network,disease resistance,sustainable agriculture,crop protection
Biomarker for Cardiovascular Risk Assessment in Europe (BIOMARCARE)

Framework: FP7 — Cooperation
Programme: Health
Destination: Translating research for human health
Action type: Collaborative project
Countries involved: Germany,Finland,Netherlands,Germany,Austria,Germany,Austria,Germany,Germany,Norway,Italy,Germany,United Kingdom,United Kingdom,France,Sweden,Estonia,Denmark,Italy,United Kingdom,Switzerland,Germany,Canada,Australia,Italy,Spain
Call:  (FP7-HEALTH-2011-two-stage, 2011)
Start date: 2011-10-01
End date: 2016-03-31
Duration (months): 54.0
Total project cost (EUR): 7847985.52
EU funding (EUR): 6000000.0
Participants: 30
Project status: CLOSED

Biomarkers are considered as tools to enhance cardiovascular risk estimation. However, the value of biomarkers on risk estimation beyond European risk scores, their comparative impact among different European regions and their role in the drive towards personalised medicine remains uncertain. Based on harmonised and standardised European population cohorts we have built significant research collaboration, expertise and infrastructure in the EU. We will apply highly innovative SME-driven technologies and perform large-scale biomarker determination to assess the predictive value of existing and emerging biomarkers. Selection of emerging biomarkers will be based on integrated cutting-edge quantitative proteomic, transcriptomic, metabolomic, and miRNomic datasets established by private and public consortium members that will be disclosed to this consortium. Existing biomarkers will be selected based on non-redundancy and their association with cardiovascular risk and phenotypes. After SME-guided development of innovative assay systems biomarkers will be tested and validated in a stepwise fashion among European populations in primary and secondary prevention. In addition to their impact on risk prediction, their association with lifestyle determinants and cardiovascular phenotypes assessed by ultrasound and MRI technique will be evaluated. We will establish a BiomarCaRE panel which leads to improved disease prediction among different European populations. International collaborations with world-class clinical trial investigators will add data on the interaction of the BiomarCaRE panel with risk-lowering medication and lifestyle changes. The outcome of SME-driven technology development and clinical validation will undergo a medical technology assessment. The determination of cost-effectiveness will guide further clinical evaluation. These studies will reveal new methods of improved cardiovascular risk estimation and will open the path towards personalised medicine.

Keywords: cardiovascular disease,risk prediction,biomarker,population based cohorts,genomics,proteomics,lifestyle,imaging,cost effectiveness
Translational Adolescent and Childhood Therapeutic Interventions in Compulsive Syndromes (TACTICS)

Framework: FP7 — Cooperation
Programme: Health
Destination: Translating research for human health
Action type: Collaborative project
Countries involved: Netherlands,United Kingdom,Germany,Israel,Ireland,Netherlands,France,United Kingdom,Germany,United States,United Kingdom
Call:  (FP7-HEALTH-2011-two-stage, 2011)
Start date: 2012-01-01
End date: 2018-06-30
Duration (months): 78.0
Total project cost (EUR): 7914883.8
EU funding (EUR): 6000000.0
Participants: 12
Project status: CLOSED

Compulsivity is characterized by a repetitive, irresistible urge to perform a behavior, the experience of loss of voluntary control over this intense urge, the diminished ability to delay or inhibit thoughts or behaviors, and the tendency to perform repetitive acts in a habitual or stereotyped manner. Compulsivity is a cross-disorder trait underlying phenotypically distinct psychiatric disorders that emerge in childhood (autism spectrum disorder, ASD; obsessive-compulsive disorder, OCD) or adolescence (substance abuse). Our approach integrates clinical data sets for ‘addictive’ (ADHD high risk for substance use), ‘anxious’ (OCD) and ‘stereotypical’ (ASD) compulsive behaviors with highly predictive animal models for new pharmacotherapy. In a series of ‘proof-of-concept’ studies, the cohesion of structural neuroimaging studies (MRI/DTI), neurochemistry (MRS/microdialysis), behavior, genetics (GWAS), proteomics and (Bayesian) machine learning tools in both male and female paediatric clinical populations and behavioral animal models will seek to better understand underlying mechanisms related to glutamate dysfunction in frontostriatal circuits and its remediation / prevention by early intervention studies with glutamate-based (riluzole and memantine) clinically used drugs. The leading drug-based interventions will be tested in pilot Phase IIb-like studies for ‘proof-of-principle’ efficacy in paediatric OCD and ASD populations. This approach will 1) establish predictive neural, genetic and molecular markers of compulsivity in pediatric populations; 2) provide evidence of disorder modifying pharmacologic strategies as a therapeutic approach; 3) develop a novel animal model for pharmaceutical screening and proof of concept studies, 4) build and valorize a translational biomarker compulsivity database and 5) provide pilot efficacy and safety data in paediatric clinical populations to support future large scale clinical trials according to these strategies.

Keywords: compulsivity,addiction,animal models,mri,genetics,human,pharmaceutical,translational,glutamate,clinical trial,children,machine learning,biomarkers,frontostriatal circuits,development
THE PRODUCTION OF A 3D HUMAN TISSUE DISEASE PLATFORM TO ENABLE REGENERATIVE MEDICINE THERAPY DEVELOPMENT (TISSUEGEN)

Framework: FP7 — Cooperation
Programme: Health
Destination: Biotechnology, generic tools and medical technologies for human health
Action type: Collaborative project
Countries involved: Sweden,Germany,United Kingdom,Netherlands,United Kingdom
Call:  (FP7-HEALTH-2011-two-stage, 2011)
Start date: 2012-01-01
End date: 2015-12-31
Duration (months): 48.0
Total project cost (EUR): 4291627.0
EU funding (EUR): 3071055.0
Participants: 5
Project status: CLOSED

This project will focus on the production of an in vitro human disease tissue platform technology to enable and accelerate the development of regenerative medicine therapies for a diverse range of diseases. The concept will be realised by the in vitro generation of 3D human tissues cultured from human induced Pluripotent Stem (iPS) cells. Initially a library of adult cells will be generated from patients with a range of genetic diseases. These cells will subsequently be used to generate iPS cell cultures in optimised conditions, with the resultant cells being differentiated into key cell types. These differentiated cells will then be integrated onto 3D tissue bioreactors operating in an optimised variable perfusion environment producing the 3D human tissue disease cultures. The bioreactors will be constructed using a range of innovative microfluidic techniques to produce systems compatible with analysis systems commonly used in laboratories worldwide. The development of a platform technology producing 3D human tissue disease cultures will enable the generation of fully differentiated cell types and thus allow diseases to be effectively modelled at a population relevant scale in 3D human tissues in vitro. The resultant major benefit of the system is that it will allow regenerative therapies to be developed and tested on batteries of human tissues in the laboratory in a rapid, cost effective manner relevant to the in vivo state. To develop and validate the platform technology within the lifetime of the project liver hepatocyte cells and tissues will be generated due to their scientific and commercial significance from a population relevant range of patients with inherited metabolic disorders (IMDs). Therefore this project will significantly advance the state of the art and constitute a significant step forward for the regenerative medicine industry producing a key platform resource.

Keywords: induced pluripotent stem cells stem cell regenerative medicine 3d tissue culture optimisation microfluidic scaffold tissue engineering
A novel generation of skin substitutes to clinically treat a broad spectrum of severe skin defects (EUROSKINGRAFT)

Framework: FP7 — Cooperation
Programme: Health
Destination: Biotechnology, generic tools and medical technologies for human health
Action type: Collaborative project
Countries involved: Switzerland,Netherlands,Germany,Netherlands,Germany,Germany,United Kingdom
Call:  (FP7-HEALTH-2011-two-stage, 2011)
Start date: 2011-10-01
End date: 2016-09-30
Duration (months): 60.0
Total project cost (EUR): 7875214.54
EU funding (EUR): 5996018.0
Participants: 10
Project status: CLOSED

Large full-thickness skin defects resulting from burns, soft tissue trauma, congenital giant nevi, tumour resection, and disease leading to skin necrosis, represent a significant and common clinical problem worldwide. This problem is far from being solved. The main challenge encountered is that most autologous skin grafting techniques are based on transplanting split-thickness skin (the today’s gold standard). Split-thickness skin contains all of the epidermis, but only remnants of the dermis. This lack of dermal tissue, frequently leads to significant scarring. Consequently, a true dermal substitute is required, which instantly exerts the cell-instructive properties of a neo-dermis. The partners of EuroSkinGraft can now offer 2 dermal substitutes, Novomaix and denovoDerm, plus the dermo-epidermal skin substitute denovoSkin. The development of all 3 substitutes was significantly supported by the FP6-program (EuroSTEC). The envisaged clinical studies are aiming strictly at a one-step surgical procedure (instead of the common two-step procedure, using Integra Artificial Skin).This is to be reached with the following protocol: Clinical application of Novomaix 1. Experimental arm 1: split-thickness skin on Novomaix applied on full-thickness wounds 2. Reference arm 1: split-thickness skin applied directly on the wound bed Clinical application of denovoDerm 1. Experimental arm 1: split-thickness skin on denovoDerm applied on full-thickness wounds 2. Reference arm 1: split-thickness skin applied directly on the wound bed Clinical application of denovoSkin 1. Experimental arm 1: denovoSkin applied on full-thickness wounds 2. Reference arm 1: split-thickness skin applied directly on the wound bed The strength of this project lies in: the high degree to which real regenerative medicine is translated into the clinic, the innovative and highly functional character of the 3 products to be tested, the central contribution of the 3 SMEs, and the excellence of the 3 clinics.

Keywords: full thickness skin defects,tissue engineering,keratinocytes,fibroblasts,collagen hydrogel,plastic compression,novomaix,denovoderm,denovoskin,split thickness skin,single step operation
Phase II clinical trial of PDGF-BB for the neurological regeneration and recovery in Parkinson´s disease (NRT)

Framework: FP7 — Cooperation
Programme: Health
Destination: Biotechnology, generic tools and medical technologies for human health
Action type: Collaborative project
Countries involved: Sweden,Sweden,United Kingdom,United Kingdom,Austria,Belgium,Germany
Call:  (FP7-HEALTH-2011-two-stage, 2011)
Start date: 2012-01-01
End date: 2015-12-31
Duration (months): 48.0
Total project cost (EUR): 8076589.43
EU funding (EUR): 5962457.7
Participants: 10
Project status: CLOSED

The goal of this project is to perform a European phase II clinical trial to demonstrate that PDGF-BB acts as a unique regenerative therapy for Parkinson’s Disease (PD), aimed at reversing the course of the disease, by promotion of endogenous brain repair mechanisms. Current pharmacological therapies for PD carry side-effects and become less effective as the disease progresses. This causes immense suffering for patients in their daily lives. There is currently no established disease-modifying, regenerative or neuroprotective treatment for PD. Such a therapy would revolutionize the capacity to effectively treat PD patients and could dramatically reduce the multi-billion € annual cost to Europe. The project will conduct a multi-centre clinical trial in PD using intracerebroventricular administration of PDGF-BB. To obtain the most relevant information from the clinical trial, state-of-the-art disease rating scales and brain imaging technology will be used to monitor changes related to restoration of brain function. Planning and conduct of the clinical study will involve investigators and advisors with extensive expertise in the disease-area and experience with participating in clinical studies. To further advance the understanding of the regenerative mechanism, preclinical studies will be performed. We will set up a framework of partners to ensure proper governance of the clinical study, compliant with fundamental ethical principles of European regulations concerning studies on “advanced therapies medicinal products”. PD patient associations and experts in ethics will assist the project with patient information and recruitment strategies. Internal training sessions, external meetings and dissemination of results will be coordinated by a communication expert firm. A robust and realistic commercialization strategy including IP, health economy and reimbursement will be developed.