GENE THERAPEUTIC STRATEGIES FOR NEUROPROTECTION - IMPLICATIONS FOR PARKINSONS-DISEASE

Gene transfer methodologies are being explored as strategies to restor e and preserve neuronal function in Parkinson's Disease. This technolo gy represents a new therapeutic modality, holding promise for continuo us and localized delivery of neuroprotective molecules. Two primary ap proaches for gene transfer have emerged: in vivo and ex vivo. Recent a dvances in the construction and characterization of gene transfer vect ors have generated more efficient vehicles to deliver and express cand idate therapeutic genes. Direct gene transfer into the CNS can be achi eved with replication-deficient viral vectors of several types: adenov irus, adeno-associated virus, and herpes simplex virus. These vector s ystems are being evaluated in models of Parkinson's disease. Strategie s to deliver genes include those that either augment dopamine biosynth esis or attenuate loss of dopaminergic neurons. A discussion of the va rious approaches is detailed. (C) 1997 Academic Press.