[Future of gene therapy for Parkinson's disease]

Parkinson's disease (PD) is a good target for gene therapy because the lesion is localized to the substantia nigra (SN). There are several approaches in gene therapy for PD. For enhancing dopamine production, the candidate genes are tyrosine hydroxylase, AADC and/or GTP cyclohydroxylase I. The second approach is a neuroprotective strategy, which is based on the usage of genes for neurotophic factors or anti-apoptotic agents. We also showed that Apaf-1-dominant negative inhibitor delivery using an AAV vector system could prevent nigrostriatal degeneration in MPTP mice, suggesting that it might be an anti-mitochondrial apoptotic gene therapy for PD. In 2003, the first gene therapy trial for PD performed at New York Weill Cornell Medical Center. The treatment is designed to deliver glutamic acid decarboxylase (GAD), the gene responsible for making GABA, into the subthalamic nucleus to "quiet down" that nucleus and alleviate Parkinson's symptoms. The last approach is replacement of disease for autosomal recessive PD. Because autosomal recessive juvenile parkinsonism (ARJP) involves the loss of function of parkin gene, gene therapy employing the parkin gene may prevent nigral cell death.