DOPAMINERGIC-NEURONS PROTECTED FROM DEGENERATION BY GDNF GENE-THERAPY

Glial cell line-derived neurotrophic factor (GDNF) supports growth and survival of dopaminergic (DA) neurons. A replication-defective adenov iral (Ad) vector encoding human GDNF injected near the rat substantia nigra was found to protect DA neurons from the progressive degeneratio n induced by the neurotoxin 6-hydroxydopamine (6-OHDA) injected into t he striatum, Ad GDNF gene therapy reduced loss of DA neurons approxima tely threefold 6 weeks after 6-OHDA lesion, as compared with no treatm ent or injection of Ad lacZ or Ad mGDNF (encoding a biologically inact ive deletion mutant GDNF). These results suggest that Ad vector-mediat ed GDNF gene therapy may slow the DA neuronal cell loss in humans with Parkinson's disease.