Adenovirus-mediated gene transfer to the central nervous system for Parkinson's disease

Abstract

Gene therapy is a potentially powerful approach to the treatment of neurological diseases. The discovery of neurotrophic factors inhibiting neurodegenerative processes and the isolation of genes encoding neurotransmitter synthesizing enzymes provide the basis for current gene therapy strategies for Parkinson's disease. Adenovirus vectors have been shown recently to allow efficient gene transfer to the brain. One of the advantages of recombinant adenovirus is that it can transduce both quiescent and actively dividing cells. Thus expression of transgenes in neurons using adenoviruses is possible after either direct in vivo gene transfer or ex vivo gene transfer. In vivo gene transfer, consisting of the direct intracerebral injection of genetic material, is a novel method that is particularly efficient with the adenoviral vector. Ex vivo gene transfer, combining gene transduction with intracerebral transplantation, is a way to improve the classical grafts which are limited by poor cell survival in Parkinson's disease. Probably because the brain is a partially immunologically privileged site, the expression of adenoviral vectors persists for several months with little inflammation. Recombinant adenoviruses are currently being improved, particularly by inactivating viral genes controlling the expression of immunodominant viral proteins.