Gene therapy to promote regeneration in Charcot-Marie-Tooth disease.
Gene therapy to promote regeneration in Charcot-Marie-Tooth disease.
复制标题
促进腓骨肌萎缩症再生的基因疗法。
DOI：
10.1016/j.brainres.2019.146533
复制
发表时间：
2020
期刊：
影响因子：
2.9
通讯作者：
Ozes,Burcak
中科院分区：
文献类型：
--
作者：
Sahenk,Zarife;Ozes,Burcak
Charcot-Marie-Tooth(CMT)神经病亚型背后的分子发病机制正变得越来越不同，因此，独立于导致基因缺陷的疾病识别共同的治疗方法是非常可取的。从临床翻译的角度来看，基因治疗方法对于最常见的脱髓鞘CMT1亚型尤其具有挑战性，这些亚型是由原发雪旺细胞遗传缺陷引起的。研究表明，远端轴突再生能力受损是原代雪旺细胞遗传缺陷远端轴突丢失的主要原因，神经营养素3(NT-3)可改善CMT1小鼠模型中受损的再生。本文综述了支持AAV1.NT-3替代基因治疗促进CMT1A神经再生的证据。总结了从主要研究的证明到评估scAAV1.tMCK.NTF3基因治疗CMT1A的I/IIa期试验的设计的翻译过程。
The molecular pathogenesis underlying Charcot-Marie-Tooth (CMT) neuropathy subtypes is becoming increasingly variable and identification of common approaches for treatment, independently of the disease causing gene defect, is therefore much desirable. Gene therapy approach from the clinical translational view point is particularly challenging for the most common “demyelinating” CMT1 subtypes, caused by primary Schwann cell genetic defects. Studies have shown that impaired regenerative capacity of distal axons is major contributing factor to distal axonal loss in primary Schwann cell genetic defects and neurotrophin 3 (NT-3) improves impaired regeneration in CMT1 mouse models. This review surveys the evidence supporting the rationale for AAV1.NT-3 surrogate gene therapy to improve nerve regeneration in CMT1A. The translational process, from proof of principal studies to the design of the phase I/IIa trial evaluating scAAV1.tMCK.NTF3 gene therapy for treatment of CMT1A is summarized.