Contrats européens
Programmes soutenus par la commission européenne
Plusieurs équipes d'I-Stem sont impliquées dans des programmes soutenus par la commission européenne dans le cadre du 6ème programme-cadre, dont l'un coordonné par Marc Peschanski (STEM-HD). Plusieurs demandes sont en cours dans le cadre des premiers appels à projets du 7ème programme-cadre.
STEM-HD
Partenaires
Institut National de la Santé et de la Recherche Medicale/I-Stem | Marc Peschanski | France |
Technion | Joseph Itskovitz | Israel |
Dialectica SRL | Dorotea Rigamonti | Italy |
University Strasbourg I | Jacques Haiech | France |
Cardiff University | Nick Allen | United Kingdom |
University of Milano | Elena Cattaneo | Italy |
Vrije Universiteit Brussel | Karen Sermon | Belgium |
Inserm Transfert SA | Christiane Dascher-Nagel | France |
Project summary
Huntington's disease (HD) is a rare hereditary brain disorder that affects men and women equally across all ethnic and racial lines. Age of onset of clinical symptoms of Huntington disease is quite variable, although the disease starts in the majority of cases at adulthood (average 35 years of age). HD is a degenerative disease whose symptoms are caused by the loss of cells in a part of the brain called the basal ganglia. Clinical symptoms are characterized by a rapidly progressive alteration of motor abilities (chorea, bradykinesia), psychological disturbances (depression and irritability) and cognitive impairment (of most functions by the later stages) leading to dementia. Death, caused by secondary complications, such as choking or infection, generally occurs about 15 to 20 years after onset. Although much has been learned about the causes and effects of HD in the last twenty years there is at present no preventative or curative therapy available and current symptomatic treatment is very limited and inadequate. HD is an autosomal, dominant monogenic disease. The mutation consists in an enlarged CAG triplet repeat that encodes an elongated stretch of polyglutamine in the N-terminal portion of the large protein huntingtin. Neither the physiological role of huntingtin, nor the molecular mechanisms of the pathology are currently known, although since its discovery a number of cellular pathways, interacting proteins and nucleic acids have been identified. The fundamental objective of the STEM-HD project is to contribute in a decisive manner to the understanding of the mechanisms of Huntington’s disease as a necessary step toward a cure. We aim at reaching two main complementary goals:
1. The deciphering of molecular mechanisms of HD,
2. The identification of compounds endowed with therapeutic potential for HD.
2. The identification of compounds endowed with therapeutic potential for HD.
To reach its goals the STEM-HD project will (i) use an available human embryonic stem (ES) cell line based upon the hypothesis that ES cells expressing a disease-related mutant gene may be used for molecular modelling of that monogenic disease; (ii) implement large-scale technological resources, and combine resource-driven and hypothesis-driven analyses at all stages in the project.
EU hESC registry, European human embryonic stem cell registry
Coordinateur: Anna Veiga (Barcelone )
Proposal abstract
Human embryonic stem cell (hESC) research holds promise for the development of therapies for degenerative pathologies, offers a tool for drug discovery and toxicity tests, for studying human development, disease physiology and gene control. hESC lines are currently derived in an increasing number of laboratories in Europe and around the world. A detailed registry of available cell lines will promote the validation and efficient use of these precious cells for research and application. Comparable information is needed about the origin of the cell lines, the methodology and standards for their derivation and the characteristics to assess their availability for research and future therapies. The growing use of hESC by the scientific community demands a high quality and comprehensive registry. The aim of the proposed European hESC registry is to promote access to all hESC lines derived in Europe and transparency about their characteristics. Only well defined and adequately characterised hESC lines according to the parameters established by the registry be listed. To determine listing decisions, the features of the cell lines will be evaluated according to defined scientific and quality standards. Data such as the origin, the derivation methodology, as well as the different parameters used for characterisation will be recorded for each hESC line in the registry. Contact data and legal status will also be available for each cell line. Each cell line will be annotated with essential and useful information on their characteristics and applications. The registry will contribute to the harmonization of the use of the reported cell lines, spreading of standards and good practice in cooperation with other international registries. It will contribute to the responsible limitation of the number of embryos needed for derivation of new cell lines by promoting access to existing hESC lines, exchange of information about these cells and transparency towards the European legislative landscape. Registry of the database and website will facilitate the continuous mapping of the research and legislative landscapes in a topographical online design. The registry will also serve as a communication and consultation platform for hESC researchers, clinical groups, patients groups and the public at large for information on hESC. A Steering Committee (StC) of national representatives with inventory and administrative tasks will be formed. One representative from each country where hESC research is performed will serve as national contact person. Updated information about the situation in each country and the cell lines that are available will be provided by the StC. A Scientific Advisory Board (SAB) is constituted of leading European scientists in the field of hESC research. The SAB will advise and assure the scientific and technical quality of the registry and serve as control body of the registry. The operational management will be coordinated by a Berlin-based information technology (IT) team and a Barcelona-based operational team, which will determine and control hESC-eligibility criteria and coordinate work with the StC and the SAB. The selection of partners will guarantee the short-term establishment of an independently managed European registry of outstanding quality, close interaction with relevant European and global
initiatives, international acceptance and global leadership.
Myelin orphan diseases in health-MYELINET
Coordinateur : Odile Bosepflug-Tanguy (Clermont-Ferrand)
The objective of the Action is to better understand and fight diseases affecting the CNS nerveinsulating myelin such as inherited leukodystrophies and white matter diseases of the premature. These pathologies are widely studied around Europe. Given the rarity of specific diseases, however, the critical mass to generate scientifically exploitable data is lacking. Therefore this action will combine a number of recognized European research groups for a coordinated approach to fight these diseases. Four working groups will be created: WG1 Functional biology and genomics / post-genomics analysis; WG2-Structural biology, proteomics and NMR analysis for the development of diagnostic tools and drug design; WG3-Prevention and new therapeutic options; WG4-Information and communication. MYELINET will promote medical, scientific and technical exchange by the creation of a common database; develop teaching, training and exchange programs for students; organise meetings and workshops; debate ethical and societal implications and concerns ofresearch issues; communicate with the public and inform affected families; and interact with experts of related diseases such as multiple sclerosis. A yearly international congress coupled to a more general public information day will be organised. This will pave the way for a more ambitious Consortium to prepare a European FP7 project.
European Network for the Advancement of Clinical Gene Transfer and Therapy-
CLINIGENE
Coordinateur : Odile Cohen-Haguenauer (Paris)
The field of gene therapy has matured and the prospects are exciting and hopeful, particularly since some treatments have now been shown to be effective in the clinic. However, precise quality and safety standards for clinical gene transfer have yet to be defined. In this context, defining optimal methods for the production of standard vector systems would pave the way for accelerated development and improved safety. This would be of enormous value to industry, individual investigators and regulators.
The goal of this proposal is the creation of a European Network for the Advancement of Clinical Gene Transfer and Therapy (CLINIGENE) integrating multidisciplinary research and development in gene therapy as well as mobilising all major stake holders involved in the development of gene therapy medicinal products: academia, industry, regulatory bodies, clinics and patients. The network will generate platform databases for particular vectors with respect to their safety and efficacy to ensure product manufacturing according to well-defined quality and safety standards in order to accelerate clinical trials. This will be achieved by compiling all available information and then ranking test and control methods by comparison, and through validation by expert partners.
The joint programme of activities comprises 1. Integration activites: sharing facilities, exchange and high-level training of personnel, e-communication and collaboration with the ESGT. 2. Research activities: six horizontal activities serving integration towards the generation of reference/standard profile data-bases - AAV, γ-retrovirus, lentivirus, adenovirus, genetically-modified cells & non-viral vectors - and four vertical activities defining a path to optimised clinical protocols - quality and efficacy (manufacture), safety (pharmtox and virus safety); pre-clinical models and novel assessment tools, clinical trials. 3. Dissemination activities: training, high-level education, communication (including a web-site with scientific & medical data-bases) and management of shared information and intellectual property rights.Within a strong integration plan, the Network is planning for flexibility in order to adapt to: (i) progresses recorded in a stepwise manner and (ii) novelty arising during the CLINIGENE workprogramme.
