The NBPS (Neurosciences Bicêtre Paris Sud) brings together a clinical department of Paediatric Neurology (Prs. P. Aubourg and M. Tardieu), a clinical Department of adult Neurology and a clinical Department of Psychiatry associated with a Department of Interventional Neuroradiology, and a Department of Neurosurgery.
The NBPS is associated with INSERM unit 1012 (Regulation of immune response, HIV-1 infection and autoimmunity, directed by M. Tardieu) and a recently installed (December 2011) INSERM unit U986 (AERES mark: A+) directed by P. Bougnères that P. Aubourg (current director of INSERM unit U745, (AERES mark: A+) and N. Cartier will join in early 2012 for the Gene Therapy of Developmental and Degenerative CNS Diseases part of it’s this research program.
The contribution of NBPS to NeurATRIS (Node 4) will focus on the paediatric component of the project and will associate specifically the Department of Paediatric Neurology and the two INSERM units. The Department of adult Neurology will allow the mid- and long-term follow-up of the paediatric patients participating in innovative therapeutic trials. The Department of Interventional Neuroradiology will investigate a gene therapy approach by local delivery into intra-cerebral arteries of viral vectors that cross the blood-brain barrier. The Neurosurgery department will be used in the future for procedures that will required a direct intervention on the brain. P. Aubourg will be the coordinator of the NBPS component that will be included in NeurATRIS (node 4). Node 4 will thus be a unique translational research structure dedicated to paediatric developmental and CNS neurodegenerative disorders:
- pushing projects from proof of concept in animal models to paediatric clinical trials, as proven by its track record in internal and external projects;
- running gene therapy clinical trials in a unique clinical setting in children with CNS disorders.
It is also important to note that these gene therapy approaches for children developed by NBPS partner (Node 4) are complementary of other therapeutic approaches developed by other nodes, but will have strong interactions with Node 1 (MIRCen) and Node 5 (BIRD). Keywords for node 4 will thus be CNS diseases in children, experimental and clinical gene therapy for CNS disorders in children.
More specifically, the platforms of NBPS include:
- The Platform (P. Aubourg and M. Tardieu) for the clinical selection and clinical investigation of paediatric CNS diseases that can be candidate for gene therapy approach.
This platform runs already 2 gene therapy trials for CNS disorders in children (X-linked adrenoleukodystrophy and MPS IIIA-SanFilipo A syndrome) and 2 other gene therapy trials are planned to start in 2012 (metachromatic leukodystrophy and MPS IIIb-SanFilipoB).This platform provides research nurses, research monitoring, quality control and data management This platform includes also a neuropsychology unit for children, 1,5 and 3 Tesla MRI, a platform for interventional neuroradiology in children and adults. The platform of U986 includes also a team dedicated to regulatory affairs with ANSM (ex-Afssaps), EMEA and FDA.
- The Platform (N. Cartier as scientific responsible) at U986 of INSERM to assess in animal and cell models preclinical gene therapy for these specific diseases.
This ressource will also serve paediatric and non paediatric projects that could come from other partners in or outside NeurATRIS. This platform is presently focused on genetic leukodystrophies, developmental neurological genetic disease (Rett syndrome), neurodegenerative CNS diseases (Alzheimer, Tauopathies, Huntington, Friedreich ataxia). Five of these projects are in house and two in collaboration. This platform will also works in close relationship with Unit 1012 of INSERM to assess immune reaction against therapeutic transgene and potentially the viral vector capsid or envelope.
We believe that it is an important asset of node 4 that platforms at NBPS allow to run clinical studies of patients and of animal models in close structures at the same site. Node 4 has already established close ties and collaboration with MIRCen (node 1) and BIRD/ABI (node 5), with which animal models, scientific projects and several technical platforms will be shared.
The platform of Clinical facilities includes the three structures necessary for CNS gene therapy projects in the same hospital: neurology, neuroradiology (paediatric and adult neuroradiology, interventional neuroradiology) and neurosurgery.
The platform at U986 of INSERM gather more than 800 m2 animal housing (1000 rodents) operating under either BCL1 or BCL2 , behavioural laboratory for rodents (motor & cognitive), neuropathological and biochemistry facilities, a laboratory dedicated to the biodistribution of viral vector into the brain and peripheral organs (3 high-throughput real-time PCR, one pyrosequencer), BCL2 cellular facility . The detailed evaluation of brain gene therapy in rodents requires the use of automatization system to quantify animal behaviour and motor function. Video capture of animal movement and behaviour are available tools that respond to these requirements.
U986 is developing with Unit 1012 a laboratory to assess the B cell and T cell response against therapeutic transgene (GLP assays for antibodies and ELISPot).