An Update on Gene Therapy in Parkinson’s Disease

Abstract

Gene therapy for Parkinson's disease (PD) may offer an alternative to current pharmacologic and surgical treatments; the former are limited by motor complications and non-motor adverse effects, and both by lack of neuroprotection. Three main strategies under investigation using gene transfer for targeted protein expression include improving availability of dopamine to the striatum with more continuous delivery, reducing activity in the subthalamic nucleus by locally inducing γ-aminobutyric acid expression, or protecting and restoring nigrostriatal neuronal function with trophic factor expression. This review summarizes the components of gene therapy for PD, the preclinical rationale for each strategy, data from the most recently published clinical trials using four different vector-gene agents, and challenges in moving gene therapy forward. Thus far, safety data from phase 1 trials have been encouraging for all four agents and one phase 2 trial suggests modest symptomatic efficacy, but definitive conclusions on efficacy cannot yet be drawn.

Synapse Assembly and Neurodevelopmental Disorders

“…With the advent of viral-based gene therapy applications almost a realistic possibility in humans (Witt and Marks, 2011), it will be important to know where and also when an intervention is critical for a successful outcome. For example, if a synaptic deficit can be overcome in the adult, then this provides hope for many adults with this form of ASD.…”

Current Experimental Studies of Gene Therapy in Parkinson's Disease

“…The conversion of levodopa to dopamine needs the enzyme acromatic L-amino acid decarbocylase (AADC) (Christine et al, 2009; Muramatsu et al, 2010). With the PD advancing, activities of AADC diminished, this further limiting dopamine level and resulted a larger need for the dosage of levodopa (Witt and Marks, 2011). The transduction of AADC gene to intrinsic striatal neurons could enhance the synthesis of dopamine and might improve the dopamine level in brain.…”

Nanotechnology—novel therapeutics for CNS disorders

“…36 Traditional gene therapy studies used viral vectors for DNA delivery, but concerns regarding the toxicity and immunogenicity of these materials have been raised. Nanotechnology offers attractive alternatives to virus-based systems.…”