诺西那生治疗脊髓性肌萎缩症有效性及安全性研究进展

许婷婷, 刘鑫, 张翠莲, 屈静晗, 张波

中国药学杂志 ›› 2022, Vol. 57 ›› Issue (17) : 1413-1418.

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中国药学杂志
PDF(942 KB)
中国药学杂志 ›› 2022, Vol. 57 ›› Issue (17) : 1413-1418. DOI: 10.11669/cpj.2022.17.003
综述

诺西那生治疗脊髓性肌萎缩症有效性及安全性研究进展

  • 许婷婷, 刘鑫, 张翠莲, 屈静晗, 张波*
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Research Progress on the Effectiveness and Safety of Nusinersen in the Treatment of Spinal Muscular Atrophy

  • XU Ting-ting, LIU Xin, ZHANG Cui-lian, QU Jing-han, ZHANG Bo*
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摘要

脊髓性肌萎缩症(spinal muscular atrophy,SMA)是由于染色体5q13.2上的运动神经元存活(survival motor neuron,SMN)1基因发生双等位基因缺失或突变引起全长SMN蛋白缺乏而导致的罕见遗传性神经肌肉疾病,发病率约为1/11 000,以脊髓前角细胞和低位脑干运动神经核变性为特征,临床表现为进行性肌无力和肌萎缩。诺西那生(Nusinersen)作为一种反义寡核苷酸(antisense oligonucleotide,ASO),通过改变SMN2基因的剪接,从而增加全功能SMN蛋白的生成来治疗SMA,已于2016年被美国食品和药品管理局批准为首个用于治疗儿童和成人SMA。本文将从作用机制、药效学、药动学、临床疗效及不良反应等方面对诺西那生进行论述,希望为诺西那生在临床中合理安全应用提供科学参考。

Abstract

Spinal muscular atrophy(SMA) is a rare hereditary neuromuscular disease caused by a biallelic deletion or mutation of the survival motor neuron(SMN) 1 gene on chromosome 5q13.2 resulting in a lack of full-length SMN protein. The incidence is about 1/11 000, characterized by degeneration of the anterior horn cells of the spinal cord and the lower brainstem motor nucleus. The clinical manifestations are progressive muscle weakness and muscle atrophy. Nusinersen, as an antisense oligonucleotide(ASO), changes the splicing of SMN2 gene to increase the production of fully functional SMN protein to treat SMA. It was approved by the U.S. Food and Drug Administration(FDA) in 2016 as the first treatment for SMA in children and adults. This article will discuss the mechanism of action, pharmacodynamics, pharmacokinetics, clinical efficacy and accessibility of nusinersen, hoping to provide scientific reference for the rational and safe application of nusinersen in clinical practice.

关键词

脊髓性肌萎缩症 / 诺西那生 / 临床疗效 / 不良反应

Key words

spinal muscular atrophy / nusinersen / clinical efficacy / adverse reaction

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许婷婷, 刘鑫, 张翠莲, 屈静晗, 张波. 诺西那生治疗脊髓性肌萎缩症有效性及安全性研究进展[J]. 中国药学杂志, 2022, 57(17): 1413-1418 https://doi.org/10.11669/cpj.2022.17.003
XU Ting-ting, LIU Xin, ZHANG Cui-lian, QU Jing-han, ZHANG Bo. Research Progress on the Effectiveness and Safety of Nusinersen in the Treatment of Spinal Muscular Atrophy[J]. Chinese Pharmaceutical Journal, 2022, 57(17): 1413-1418 https://doi.org/10.11669/cpj.2022.17.003
中图分类号： R95   

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基金

中国医学科学院医学与健康科技创新工程项目资助(2021-I2M-1-003)
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