Promoter-activated expression of nerve growth factor for treatment of neurodegenerative diseases

Genetic transfer approaches have received recent consideration as potential treatment modalities for human central and peripheral nervous system (CNS and PNS, respectively) neurodegenerative disorders, including Parkinson's d isease, Alzheimer's disease, and amyotrophic lateral sclerosis. Transplanta tion of genetically modified cells into the brain represents a promising st rategy for the delivery and expression of specific neurotrophic factors, ne urotransmitter-synthesizing enzymes, and cellular regulatory proteins for i ntervention in neurodegenerative diseases. The use of specific regulatable promoters may also provide potential contro l of gene expression required for dose-specific or time-specific therapeuti c strategies. in this article, we review the potential use of activated pro moters in ex vivo systems for the potential genetic therapy of neurodegener ative disorders, and then describe our own studies using the zinc-inducible metallothionein promoter for the regulated expression of nerve growth fact or (NGF) in rodent brain transplants.