ADENOVIRUS VECTOR-MEDIATED GENE-TRANSFER INTO HUMAN EPILEPTOGENIC BRAIN-SLICES - PROSPECTS FOR GENE-THERAPY IN EPILEPSY

As a first step in the development of a gene therapy approach to epile psy, we evaluated the ability of adenovirus vectors to direct the tran sfer into and expression of a marker gene in human brain slices obtain ed from patients undergoing surgery for medically intractable epilepsy . Following injection of adenovirus vectors containing the Escherichia coli lacZ gene into hippocampal and cortical brain slices, lacZ mRNA, beta-galactosidase protein, and enzymatic activity were detected, con firming successful gene transfer, transcription, and translation into a functional protein. Transfected cells were predominantly glial, with some neurons expressing P-galactosidase as well, These results suppor t the potential of adenovirus vectors to transfer genetic information into human epileptogenic brain, resulting in expression of the gene in to a functional protein, These findings also have implications for the development of gene therapy approaches to certain seizure disorders. A number of potential therapeutic approaches are discussed, including the elevation of inhibitory neurotransmitter or neuropeptide levels, e xpression or modulation of postsynaptic receptors, and manipulation of signal transduction systems. 1997 Academic Press.