Strategies of Gene Therapy for Parkinson’s Disease

Abstract

Parkinson’s disease (PD) is a progressive neurodegenerative condition primarily involving the loss of dopaminergic neurons of the substantia nigra pars compacta (SNpc). This leads to a variety of symptoms and signs, including the primary motor deficits of tremor, bradykinesia, and rigidity, as well as other nonmotor problems such as cognitive, affective, and autonomic disturbances that may have pathology outside of this dopaminergic pathway degeneration. Of all neurological diseases, PD has several features that make it one of the most promising targets for clinical gene therapy. The internment of the major pathology to a compact localized neuronal population and the anatomy of the basal ganglia circuitry demonstrate that global gene transfer is not required, and there are well-defined sites for gene transfer. This review summarizes the studies of gene transfer using viral vectors and three separate gene transfer strategies currently being pursued for PD.