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Potential therapeutic effect of the GAD gene transfer in kainic acid-induced excitotoxicity


Epilepsies. Volume 13, Number 2, 109-12, Avril - Mai - Juin 2001, Articles originaux

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Author(s) : C. Brana, C. Leré, S. Arthaud, A. Rougier, S. Millecamps, J. Mallet, G. Le Gal La Salle

Summary : The recent development of efficient gene transfer into central nervous system allows the prospect of new strategies for the treatment of drug-resistant neurological diseases such temporal lobe epilepsy. Our strategy is based of the increased GABA inhibition by using recombinant adenovirus vector carrying GAD gene which encode the enzyme synthesizing GABA. The aim of this study is to evaluate the potential therapeutic effects of GAD 67 gene transfer in an in vitro kainic acid -induced excitotoxic model (organotypic cultures). We used two non replicative recombinant adenovirus vectors encoding the same gene, one under the control of the Rous sarcoma virus Long Terminal Repeat promoter able to express the transgene in neurons and glial cells, and one under the control of the rat neuron-specific enolase promoter to target gene expression to neurons. We have shown with both vectors an overexpression of the GAD 67 protein into hippocampal cells in vitro and also in vivo. The next step will be to test gene transfection in experimental models of epilepsy.

Keywords : organotypic cultures, epilepsy, GAD, adenovirus, gene transfer.

 

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