Brain Repair and Imaging in Neural Systems, Department of Experimental and Medical Science, Lund University, Lund, Sweden.
Mov Disord. 2010;25 Suppl 1:S161-73. doi: 10.1002/mds.22785.
The once fantastic theoretical concept that patients with Parkinson's disease (PD) would receive gene therapy in an attempt to alleviate their symptoms and potentially modify the course of their disease has become a reality. On the basis of positive preclinical data, four different gene therapy approaches are currently in Phase I or Phase II clinical trials. Some approaches are intended to increase levels of endogenous dopamine or enhance the function of the prodrug levodopa. Others are intended to normalize basal ganglia circuitry by reducing the PD-related overactivity of specific brain structures such as the subthalamic nucleus. Each is intended for symptomatic benefit. Finally, gene delivery of trophic factors that not only augment dopaminergic function but are potentially disease modifying has a strong preclinical database and are also in clinical trials. Each of these approaches is discussed in the present review.
曾经有一个美妙的理论概念，即帕金森病（PD）患者将接受基因治疗，以试图缓解他们的症状，并可能改变疾病的进程。基于积极的临床前数据，目前有四种不同的基因治疗方法处于 I 期或 II 期临床试验阶段。一些方法旨在增加内源性多巴胺的水平或增强前药左旋多巴的功能。其他方法旨在通过减少丘脑底核等特定脑结构的与 PD 相关的过度活跃来使基底神经节回路正常化。每种方法都旨在带来症状上的益处。最后，神经传递营养因子的基因治疗不仅增强了多巴胺能功能，而且具有潜在的疾病修饰作用，具有强大的临床前数据库，也正在进行临床试验。本综述讨论了这些方法中的每一种。
