Multi-site partitioned delivery of human tyrosine hydroxylase gene with phenotypic recovery in Parkinsonian rats

Parkinson's disease (PD) is a leading candidate for neurological gene thera py, given our increasing knowledge of the functional anatomy of the striato nigral system and the localized nature of the affected cell populations. He re we report that stereotactic introduction of a human tyrosine hydroxylase (TH-2) gene using multi-site partitioned doses resulted in behavioral reco very in 6-OHDA-lesioned rats, with transient 100% recovery observed in some animals. We also show correlation between numbers of TH-immunoreactive cel ls and loss of apomorphine induced rotation, with a near-linear relationshi p between TH expression and phenotypic recovery. Furthermore, the data sugg est that only a fraction of striatal cells need to be transduced in order t o exert phenotypic effects, and therefore TH partitioned gene transfer may have clinical potential in PD. NeuroReport 11:1145-1151 (C) 2000 Lippincott Williams & Wilkins.