Gene therapy in neurological disease

Abstract

Advances in the area of stroke and other neurodegenerative disorders have identified a variety of molecular targets for potential therapeutic intervention. The use of modified viral vectors has now made it possible to introduce foreign DNA into central nervous system cells, permitting overexpression of the protein of interest. A particular advantage of the herpes simplex system is that the herpes virus is neurotropic and is therefore suited for gene therapy to the nervous system. The vectors used by our group to date utilize an amplicon-based bipromoter system, which permits expression of both the gene of interest and a reporter gene. Using this strategy, we have been successful in transferring potentially neuroprotective genes to individual central nervous system cells. Using this approach, it is possible to show that gene therapy both before and after insult is feasible. Some limitations of this technique exist, the main one being delivery and extent of transfection. Although application to clinical stroke is probably remote, viral vector-mediated gene therapy provides a unique and powerful tool in the study of molecular mechanisms involved in brain injury.