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

In vivo gene delivery in the basal ganglia.

In vivo gene delivery in the brain using adeno-associated virus-based (AAV) vectors. We have shown that AAV vectors can drive stable gene expression (at least one year) in the brain with however a variable efficacy and durability. In the globus pallidus, gene expression es early and efficient whereas in the striatum, a potential target for the treatment of Huntington and Parkinson's diseases, it  is stable but not efficient. New vectors developed in another theme are currently evaluated.

Improvement of the survival and functionality of fetal grafts for Parkinson's disease.

Ex vivo gene delivery to fetal nervous tissue used for cell replacement therapy by means of adeno-associated viruses (AAV)-based vectors. We have shown that AAV vectorsare particularly efficient to transfer genes in human embryonic mesencephalon. New constructs expressing protective factors will be developped to improve the survival of the transplanted cells. In collaboration with M. Peschanski (INSERM, Paris), AAV-mediated transfer of GDNF (glial cell line-derived neurotrophic factor) gene promoting dopaminergic neuron survival, into the embryonic mesencephalon prior to transplantation.