杜氏肌营养不良症的基因和细胞治疗临床试验进展

Clinical trials progress of gene and cell therapy for Duchenne muscular dystrophy

杜氏肌营养不良症(DMD)是罕见的致死性X连锁隐性遗传病,系DMD基因突变导致肌营养不良蛋白(dystrophin)缺乏引发。患者主要表现为进行性肌无力、肌萎缩并最终死于心肺衰竭,尚无有效治疗方法。目前开展的临床试验主要包括恢复dystrophin表达的基因治疗,及移植表达dystrophin并具备正常功能的细胞治疗方法。其中基因治疗包括无义突变通读、外显子跳跃、腺相关病毒载体介导的dystrophin基因替代和基因编辑疗法。细胞治疗包括同种异体心肌球衍生细胞和嵌合细胞疗法。

Duchenne muscular dystrophy(DMD)is a rare fatal lethal X-linked recessive muscle dystrophy which caused by mutations in the dystrophin gene.Patients with DMD have an absence of functional dystrophin protein,which leads to progressive muscle weakness and muscular atrophy,and ultimately causing premature death from respiratory failure and heart failure.There is currently no cure for DMD.Active clinical trials are ongoing to develop two therapeutic strategies.One therapeutic strategy is targeted gene therapy,which is mainly aimed at restoring the expression of dystrophin,including read-through therapy,exon skipping therapy,adeno-associated virus vector mediated gene replacement therapy and gene editing therapy.Another therapeutic strategy is targeted cell therapy,which are mainly aimed at transplanting healthy cells to achieve a full function recovery,including allogeneic cardiosphere-derived cells and dystrophin expressing chimeric cells.