Nagabhushan Kalburgi Sahana, Khan Nadia N, Gray Steven J
Gene Therapy Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Discov Med. 2013 Feb;15(81):111-9.
The past few years have seen rapid advancements in vector-mediated gene transfer to the nervous system and modest successes in human gene therapy trials. The purpose of this review is to describe commonly-used viral gene transfer vectors and recent advancements towards producing meaningful gene-based treatments for central nervous system (CNS) disorders. Gene therapy trials for Canavan disease, Batten disease, adrenoleukodystrophy, and Parkinson's disease are discussed to illustrate the current state of clinical gene transfer to the CNS. Preclinical studies are under way for a number of diseases, primarily lysosomal storage disorders, using a newer generation of vectors and delivery strategies. Relevant studies in animal models are highlighted for Mucopolysaccharidosis IIIB and Krabbe disease to provide a prelude for what can be expected in the coming years for human gene transfer trials, using recent advancements in gene transfer technology. In conclusion, recent improvements in CNS gene transfer technology are expected to significantly increase the degree of disease rescue in future CNS-directed clinical trials, exceeding the modest clinical successes that have been observed so far.
在过去几年中，载体介导的基因向神经系统的转移取得了快速进展，并且在人类基因治疗试验中也取得了一定成功。本综述的目的是描述常用的病毒基因转移载体以及在为中枢神经系统（CNS）疾病开发有意义的基于基因的治疗方法方面的最新进展。讨论了针对卡纳万病、巴顿病、肾上腺脑白质营养不良和帕金森病的基因治疗试验，以说明目前向中枢神经系统进行临床基因转移的现状。目前正在针对多种疾病开展临床前研究，主要是溶酶体贮积症，采用了新一代的载体和递送策略。重点介绍了在黏多糖贮积症IIIB型和克拉伯病动物模型中的相关研究，以便为未来人类基因转移试验利用基因转移技术的最新进展奠定基础。总之，中枢神经系统基因转移技术的最新改进有望在未来针对中枢神经系统的临床试验中显著提高疾病挽救程度，超越迄今为止所观察到的有限临床成功。
