Human gene therapy approaches for the treatment of Parkinson's disease: An overview of current and completed clinical trials

Abstract

Gene therapy has been employed in the human brain for a number of disorders in clinical trials and may serve as an avenue for the treatment of Parkinson's disease (PD). Several gene therapy treatment strategies have been developed and evaluated in patients with PD. Three main strategies have been used-enhancement of dopamine synthesis, expression of trophic factors, and neuromodulation. Typically, genes are delivered via viral vectors and expressed within neurons in PD-relevant areas of the brain such as the striatum. These methods of gene delivery have the potential for long-term expression and may only need to be delivered once. Notably, current gene therapy strategies do not address the non-motor symptoms of PD and do not curtail α-synuclein aggregation/spread. Furthermore, many of the completed trials were open-label trials and are subject to placebo effects and bias. Clinical trials have, however, demonstrated safety and studies are ongoing. Here, we review the current landscape of the development of gene therapy for PD and discuss the future of this novel treatment strategy.