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

Study of the limiting steps in AAV-mediated gene transfer and development of improved vectors.

In the basal ganglia, recombinant vectors for gene transfer based on adeno-associated virus (AAV), a single-standed virus, transduce neurons of the globus pallidus and substantia nigra with a high efficiency. In contrast, transduction effeciency is low in the striatum. In order to identify the limiting steps in AAV-mediated gene transfer in the striatum, new vectors are currently evaluated: I) self-complementary vectors allowing the formation of double-standed DNA without the need for a cellular factor; II) non-viral vectors consisting in recombinant capsid protein of JCV, a papovavirus with a natural tropism for glial cells in the brain (collaboration with W. Lüke) and AAV DNA.