In VivoAdenovirus-Mediated Gene Transfer for Parkinson's Disease

Abstract

Gene therapy is a potentially powerful approach to the treatment of neurological diseases. Neurotransmitter synthesizing enzymes and neurotrophic factors inhibiting neurodegenerative processes provide the basis for current development of gene therapy strategies for Parkinson's disease. Recently,in vivogene transfer to the brain has been developed using adenovirus vectors. One of the advantages of recombinant adenovirus is that it can transduce both quiescent and actively dividing cells, thereby allowing both directin vivogene transfer andex vivogene transfer to neural cells. The expression of adenoviral vectors persists for several months with little inflammation, probably because the brain is partially protected from the immune system. Recombinant adenoviruses are currently being improved, particularly by inactivating viral genes controlling the expression of immunodominant viral proteins. Novel therapeutic tools such as vectors for gene therapy have to be evaluated in terms of efficacy and safety for future clinical trials. These vectors still need to be improved to allow long-term and possibly regulatable expression of the transgene.