Units

Laboratory of Experimental Neurosurgery

The group is composed of 1 MD, phD (Marc Levivier), 2 MD (Florence Lefranc, Alphonse Lubansu), 1 PhD (Liliane Tenenbaum), 2 PhD students (Abdel Chtarto, Enni Lehtonen), 1 Master Student and 1 Technician (Catherine Melas) working in close collaboration with the Laboratory of Molecular Oncology and Gene Transfer (Prof. T. Velu). The group is exploring novel therapeutic approaches for Parkinson's and Huntington's diseases: I) ex vivo gene delivery to fetal nervous tissue used for cell replacement therapy by means of adeno-associated viruses (AAV)-based vectors. AAV vectors particulary efficient to transfer genes in human embryonic mesencephalon will be used to improve the survival of the transplanted cells of GDNF (glial cell line-derived neurotrophic factor) gene promoting dopaminergic neuron survival, into the embryonic mesencephalon prior to transplantation. II) in vivo gene delivery in the basal ganglia. Current AAV vectors transfer genes in the striatum at low efficiency. III) Study of the limiting steps in AAV-mediated gene transfer and development of improved vectors. IV) AAV vectors carrying tetracyclin-inducible promoter to modulate gene expression (ex vivo and in vivo) in the brain.

Projetcs

Mechanisms of intracerebral transplantation in experimental models of neurodegenerative disorders

Study of the mechanisms of action of intracerebral implantation of foetal neurons in experimental models for Huntington's and Parkinson's diseases. Particularly,  study of the neuroprotective and neurotrophic effects of intracerebral grafts of fetal neurons. We have evaluated the effects of fetal striatal grafts in an excitotoxic model for Huntington'disease consisting in injecting quinolinic acid, an agonist of NMDA receptor, in the adult rat striatum. We have shown that, although the grafted cells are poorly maintained, functional improvements could be observed (A. Lubansu).  A higher survival of the grafted tissue could allow to enhance reinervation and improve the clinical benefit.