Gene therapy progress and prospects: Parkinson's disease.

Abstract

GeriatricResearch, Education and Clinical Center (GRECC), Pittsburgh VA Healthcare System, Pittsburgh, PA, USAGene Therapy (2003) 10, 1721–1727. doi:10.1038/sj.gt.3302116PD is an attractive target for central nervous system(CNS) gene therapy for several reasons. First, thepathology in early PD is, to a first approximation, limitedto dopaminergic neurons projecting from the substantianigra pars compacta (SNc) to the caudate aputamenl, sothat localized gene delivery is a viable therapeuticstrategy. Second, the neurochemical deficits and thefunctional consequences of dopaminergic cell loss onlocal basal ganglia circuitry are well characterized; genetransfer can be designed either to improve cell survival,or to modify functional activity in the damaged basalganglia circuitry (summarized in Figures 1 and 2). Third,PD is common and disabling despite treatment; nocurrent intervention is uniformly accepted as altering thenatural history of disease progression; hence, develop-ment of novel therapeutics is desirable. A variety oftherapeutic transgenes has been delivered in experi-mental models of PD, using a number of differentvectors. In this article, we survey the literature from2000 to 2003, and briefly review recent progress in thedevelopment of gene transfer strategies for treating PD.