Preclinical development of gene therapy for Parkinson's disease

Abstract

Multiple targets and pathways may be amenable to the development of gene therapy approaches for Parkinson's disease. This article discusses some of the cellular and brain circuit pathways relevant to Parkinson's disease that would be clinically amenable to gene therapy. Approaches could be classified according to two main categories, i.e. symptomatic vs. neuroprotective/neurorestorative strategies. Examples of the different possibilities currently in development are given and feature both dopaminergic and non-dopaminergic symptomatic treatments of parkinsonian symptoms and/or L-DOPA-induced side effects, anti-apoptotic neuroprotective strategies and growth-factor delivery for neuroprotection/neurorestoration. While gene therapy has been mostly used so far for enhancing the expression of the target gene, the use of dominant negative or siRNA opens new possibilities. This, combined with the key feature of gene delivery that offers access to intracellular signalling pathways, is likely to further expand the number of proposed targets to be studied.