Parkinson's disease: gene therapies

Abstract

With the recent development of effective gene delivery systems, gene therapy for the central nervous system is finding novel applications. Here, we review existing viral vectors and discuss gene therapy strategies that have been proposed for Parkinson's disease. To date, most of the clinical trials were based on viral vectors to deliver therapeutic transgenes to neurons within the basal ganglia. Initial trials used genes to relieve the major motor symptoms caused by nigrostriatal degeneration. Although these new genetic approaches still need to prove more effective than existing symptomatic treatments, there is a need for disease-modifying strategies. The investigation of the genetic factors implicated in Parkinson's disease is providing precious insights in disease pathology that, combined with innovative gene delivery systems, will hopefully offer novel opportunities for gene therapy interventions to slow down, or even halt disease progression.

Figure 1.

The different enzyme replacement therapy approaches in PD. Enzyme replacement therapies aim at compensating the decrease of striatal dopamine release caused by the degeneration of the nigral dopaminergic neurons, by inducing ectopic dopamine synthesis in the striatum.

Figure 2.

Current status of the different gene therapy approaches in PD.