Gene-based therapies in Parkinson's disease.

Parkinson's disease (PD) is a progressive neurological disorder characterized primarily by the degeneration of nigrostriatal dopaminergic neurons and diminution of the neurotransmitter dopamine. Though dopamine replacement therapies such as levodopa can improve the symptoms of PD, the benefits may be overshadowed by side effects and the onset of symptoms not responsive to dopaminergic treatments (e.g., autonomic symptoms, gait and balance problems, and cognitive impairment). Furthermore, no therapies have proven to slow the neurodegenerative process. Novel approaches to address these difficult problems, and others, are being sought. Over the last decade, several innovative gene therapies for PD have entered human clinical trials in an effort to address both symptomatic and potential disease-modifying effects. Though the results of these trials have been mixed, the therapies have generally been safe and well-tolerated, suggesting gene therapy may be a viable treatment for PD in the future. This article will review past and current clinical trials of gene therapies for PD. In addition, novel preclinical approaches to gene therapy for PD will be described.