药学学报, 2022, 57(5): 1301-1311
引用本文:
贺志昊, 张翔*. 作用于SMN2的脊髓性肌萎缩治疗药物研究进展[J]. 药学学报, 2022, 57(5): 1301-1311.
HE Zhi-hao, ZHANG Xiang*. Advances in drugs on targeting SMN2 for the treatment of spinal muscular atrophy[J]. Acta Pharmaceutica Sinica, 2022, 57(5): 1301-1311.

作用于SMN2的脊髓性肌萎缩治疗药物研究进展
贺志昊, 张翔*
中国医学科学院、北京协和医学院药物研究所, 活性物质发现与适药化研究北京市重点实验室, 北京 100050
摘要:
脊髓性肌萎缩(spinal muscular atrophy,SMA)是一种严重的遗传性神经肌肉疾病,由于其存活运动神经元1(survival motor neuron,SMN1)基因缺失或突变导致其编码的SMN蛋白水平降低,引起α神经元的缺失和进行性肌肉萎缩,导致运动功能的丧失和寿命的缩短。研究发现,促进SMN2基因中外显子7的包含,可产生具有完全功能的SMN蛋白,改善疾病的症状。迄今为止,包含基因治疗药物onasemnogene abeparvovec在内,只有3种用于SMA的治疗药物上市。本文简要介绍了反义寡核苷酸药物诺西那生钠(nusinersen)和小分子化学药物利司扑兰(risdiplam),并综述了处于临床及临床前研究阶段的以SMN2为靶点的小分子化学药物和反义寡核苷酸药物的研究进展。
关键词:    脊髓性肌萎缩      诺西那生钠      利司扑兰      反义寡核苷酸     
Advances in drugs on targeting SMN2 for the treatment of spinal muscular atrophy
HE Zhi-hao, ZHANG Xiang*
Beijing Key Laboratory of Active Substance Discovery and Druggability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
Abstract:
As one of the most serious hereditary neuromuscular disease, spinal muscular atrophy (SMA) is caused by the loss or mutation of survival motor neuron 1 (SMN1) gene. It leads to a decrease in the level of SMN protein and a consequent loss of alpha neurons and progressive muscle atrophy resulting in the progressive muscle weakness, the significant disability and the shortened lifespan. Up till now, only three drugs have been approved for SMA, including the gene therapy drug onasemnogene abeparvovec. The antisense oligonucleotide drug nusinersen and and the small molecule chemical drug risdiplam were briefly introduced. Some representative samples of the small molecule chemical drugs and antisense oligonucleotide drugs targeting SMN2 in the clinical trial or preclinical research phases were also reviewed.
Key words:    spinal muscular atrophy    nusinersen    risdiplam    antisense oligonucleotides   
收稿日期: 2022-01-14
DOI: 10.16438/j.0513-4870.2022-0062
基金项目: 中国医学科学院医学与健康科技创新工程(2021-I2M-1-054).
通讯作者: 张翔,Tel:86-10-63165248,E-mail:simon@imm.ac.cn
Email: simon@imm.ac.cn
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