脊髓性肌萎缩症疾病修正治疗真实世界研究进展

doi:10.12372/jcp.2025.23e0998

摘要/Abstract

摘要：

脊髓性肌萎缩症（SMA）是一种遗传性的神经肌肉疾病，会导致患者出现渐进式的肌无力和肌萎缩，严重者甚至死亡。近年来，SMA修正治疗药物的出现，极大地改善了患者的临床症状及提升了患者的生活质量。此类药物的长期有效性和安全性，以及对疗效的各种影响因素尚未明确，需进一步监测和研究。本文通过对SMA修正治疗药物的真实世界有效性、安全性研究进行综述，以期对SMA精准化及个体化治疗提供一些新启发及思考。

关键词: 脊髓性肌萎缩症, 疾病修正治疗, 有效性, 安全性, 真实世界研究

Abstract:

Spinal muscular atrophy (SMA) is a genetic neuromuscular disorder that leads to muscle weakness, atrophy, and which can lead to death in severe cases. Recently, therapeutic drugs that can modify SMA have emerged and have significantly improved the clinical symptoms and the quality of life of patients. However, the long-term efficacy and safety of these drugs are not yet established, and various confounding factors affecting drug efficacy need further analysis and study. This article reviews the real-world efficacy and safety studies of drugs for SMA modification drugs, intending to provide some new inspirations and thaughts for the precision and individualized treatment of SMA.

Key words: spinal muscular atrophy, disease-modifying therapy, efficacy, safety, real-world research

吴献, 刘艳, 刘昕竹, 黄晓会, 马婧, 徐阿晶, 幸小东, 蒋文高, 张健. 脊髓性肌萎缩症疾病修正治疗真实世界研究进展[J]. 临床儿科杂志, 2025, 43(1): 61-69.

WU Xian, LIU Yan, LIU Xinzhu, HUANG Xiaohui, MA Jing, XU A-jing, XIN Xiaodong, JIANG Wengao, ZHANG Jian. Advances in real-world research on disease-modifying treatments for spinal muscular atrophy[J]. Journal of Clinical Pediatrics, 2025, 43(1): 61-69.

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名称	诺西那生	索伐瑞韦	利司扑兰
给药方式	鞘内注射	静脉注射	口服
给药剂量	12 mg (5 mL)	1.1×10¹⁴ vg·kg^-1	16日龄~<2月龄，0.15 mg·kg^-1；2月龄~<2岁，0.20 mg·kg^-1；≥2岁(<20 kg），0.25 mg·kg^-1；≥2岁(≥20 kg），5 mg
作用机制	增加SMN2 mRNA 转录本中外显子7的包含和全长SMN蛋白的生成	使用scAAV9作为载体，将正常的SMN1基因导入神经细胞，以产生全长SMN蛋白质	增加SMN2 mRNA 转录本中外显子7的包含和全长SMN蛋白的生成
给药频率	在第0、14、28和63天使用4次负荷剂量，此后每4个月使用1次维持剂量	一次性注射	每天一次
FDA批准的使用年龄范围	无	<2岁	≥16日龄
治疗限制	无法进行腰椎穿刺	存在AAV9抗体	药物相互作用
不良事件	头痛，呕吐，背痛等	转氨酶升高，呕吐等	发热，皮疹，腹泻等
监测事项	腰椎穿刺后的不良反应，血小板计数，凝血功能，肾功能等	血小板计数，心肌肌钙蛋白I	胚胎-胎儿毒性

患者分型	日常活动	功能状态	生活质量
不可独坐者	RULM CHOP ATEND ROM	SMAFRS	SF-36
可独坐（不可站立）者	RULM HFMSE MFM-32 ROM	SMAFRS	SF-36
可独坐（可辅助站立）者	RULM HFMSE MFM-32	SMAFRS	SF-36
可行走者	HFMSE MFM-32	SMAFRS TUGT 6MWT	SF-36