Nanou Aikaterini, Azzouz Mimoun
Academic Neurology Unit, University of Sheffield, Sheffield, UK.
Prog Brain Res. 2009;175:187-200. doi: 10.1016/S0079-6123(09)17513-1.
Gene therapy approaches to treat inherited and acquired disorders offer many unique advantages over conventional therapeutic approaches. For neurodegenerative diseases, gene therapy is particularly attractive due to the restricted bioavailability of conventional therapeutic substances to the affected structures of the brain and progressive nature of these diseases. With the development of lentiviral vector systems, many issues have been addressed and new delivery routes to the nervous system have been identified. Lentiviral vectors can efficiently deliver genes to postmitotic neuronal cell types offering long-term expression, can be generated in high titers, and do not give immunological complications. Various animal studies have demonstrated the effectiveness of these vectors to deliver therapeutic genes into the nervous system, as well as to model human diseases. This chapter will describe the basic features of lentiviral vectors, the progress, and their applications as a therapeutic strategy to treat diseases such as amyotrophic lateral sclerosis, spinal muscular atrophy, Parkinson's disease, and Huntington's disease.
与传统治疗方法相比,用于治疗遗传性和后天性疾病的基因治疗方法具有许多独特优势。对于神经退行性疾病,由于传统治疗物质对大脑受影响结构的生物利用度有限以及这些疾病的进行性本质,基因治疗尤其具有吸引力。随着慢病毒载体系统的发展,许多问题已得到解决,并且已确定了新的神经系统递送途径。慢病毒载体可以有效地将基因递送至有丝分裂后神经元细胞类型,实现长期表达,可以高滴度产生,并且不会引发免疫并发症。各种动物研究已经证明了这些载体将治疗性基因递送至神经系统以及模拟人类疾病的有效性。本章将描述慢病毒载体的基本特征、进展及其作为治疗策略在治疗诸如肌萎缩侧索硬化症、脊髓性肌萎缩症、帕金森病和亨廷顿舞蹈症等疾病中的应用。