26 - A Defective Herpes Simplex Virus Vector System for Genetic Intervention in the Adult Brain: Applications to Gene Therapy and Neuronal Physiology

Abstract

This chapter describes a defective herpes simplex virus (HSV) vector system for genetic intervention in the adult brain. The system can support gene transfer into neurons and glia in culture or in the adult rat brain. Thus, HSV-1 vectors are likely to be useful both for studying neuronal physiology and brain functions and for performing gene therapy on neurological disorders. A strategy is also developed for studying neuronal physiology and brain functions by expressing the catalytic domains of signal transduction enzymes. By using this approach, it was established that an unregulated adenylate cyclase causes a long-term increase in neurotransmitter release from cultured neurons. Initial results suggest that expressing these unregulated signal transduction enzymes from cell type-specific promoters in the adult brain can alter brain function and affect specific behavioral responses. A potential therapeutic approach to Parkinson's disease is to express the tyrosine hydroxylase gene in striatal cells. Expression of neurotrophic factors may be useful for treating specific neurodegenerative diseases.