脊髓性肌萎缩症遗传学及治疗研究进展

摘要

脊髓性肌萎缩症(SMA)是由于脊髓前角运动神经元退化引起的神经肌肉性疾病,新生儿患病率约为1/6000~1/10000,全球不同人群的基因携带频率为1/40~1/50,是造成婴幼儿死亡最常见的常染色体隐性遗传病之一.SMA这一称谓主要指由SMN1基因突变所致的SMN1依赖性SMA.由于基因检测的无创性和特异性,使其逐渐发展成为诊断SMA的金标准.SMA尚无特异的治疗方法 ,除了常规的神经营养、肌肉锻炼等方法 外,当前研究的热点,组蛋白脱乙酰酶(HDAC)抑制剂类药物为迄今为止唯一完成Ⅲ期临床试验的药物.此外,小分子SMN增强剂、诱导多能干细胞(iPSC)技术、反义寡核苷酸纠正SMN2的剪接错误等治疗方法 ,目前尚处于体外实验阶段.文章就SMA近年的遗传学及治疗研究进展作一综述.%Spinal muscular atrophy (SMA) is a group of neuromuscular disorders, caused by degeneration of the motor neurons in the anterior horn of the spinal cord, with prevalence of about 1 in 6000 to 1 in 10000 in newborn. The gene carrying frequency is about 1 in 40 to 1 in 50 all over the world. SMA is one of the most common autosomal recessive diseases causing infant death. SMA mainly refers to SMN1 dependent caused by SMN1 gene mutations. Noninvasiveness and specificity make genetic testing a recommended method for diagnosis of SMA. In addition to conventional methods such as neural nutrition, muscle exercise, etc., there is no specific treatment for SMA up to now. Nevertheless, HDAC inhibitors deserve attention as they are the only drugs completed Phase Ⅲ clinical trials to date. Furthermore, other ways as small-molecule SMN enhancers, induced pluripotent stem cell (iPSC), antisense oligonucleotides to correct SMN2 splicing, etc, were still on the way of in vitro stage at present.