Department of Neurology, University of California, San Francisco, San Francisco, CA 94115, USA.
Curr Neurol Neurosci Rep. 2011 Aug;11(4):362-70. doi: 10.1007/s11910-011-0197-8.
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.
基因治疗帕金森病（PD）可能为目前的药物治疗和手术治疗提供替代方法；前者受到运动并发症和非运动不良反应的限制，两者都缺乏神经保护作用。使用基因转移进行靶向蛋白表达的三种主要策略包括通过更持续的输送提高多巴胺向纹状体的可用性，通过局部诱导γ-氨基丁酸表达降低丘脑底核的活性，或通过表达营养因子保护和恢复黑质纹状体神经元功能。这篇综述总结了 PD 基因治疗的组成部分，每种策略的临床前原理，最近使用四种不同载体基因药物进行的临床试验的数据，以及推动基因治疗前进的挑战。到目前为止，所有四种药物的 1 期临床试验的安全性数据令人鼓舞，一项 2 期临床试验表明有一定的症状疗效，但尚不能得出确切的疗效结论。
