Gene therapeutic strategies for neuroprotection: implications for Parkinson's disease

Gene transfer methodologies are being explored as strategies to restore and preserve neuronal function in Parkinson's Disease. This technology represents a new therapeutic modality, holding promise for continuous and localized delivery, of neuroprotective molecules. Two primary approaches for gene transfer have emerged: in vivo and ex vivo. Recent advances in the construction and characterization of gene transfer vectors have generated more efficient vehicles to deliver and express candidate therapeutic genes. Direct gene transfer into the CNS can be achieved with replication-deficient viral vectors of several types: adenovirus, adeno-associated virus, and herpes simplex virus. These vector systems are being evaluated in models of Parkinson's disease. Strategies to deliver genes include those that either augment dopamine biosynthesis or attenuate loss of dopaminergic neurons. A discussion of the various approaches is detailed.