Nusinersen as a Therapeutic Agent for Spinal Muscular Atrophy

被引：5

作者：

Li, Qing ^{[1
]}

机构：

[1] ShiJiaZhuang Tradit Chinese Med Hosp, Dept Fus, 233 ZhongShan West Rd, Shijiazhuang 050051, Hebei, Peoples R China

来源：

YONSEI MEDICAL JOURNAL | 2020年 / 61卷 / 04期

关键词：

Nusinersen; survival of motor neuron gene; phosphonothioate antisense oligonucleotides; exon splicing; cellular uptake; blood-brain barrier; RECEPTOR-MEDIATED UPTAKE; FUNCTIONAL MOTOR SCALE; ANTISENSE OLIGONUCLEOTIDE; CELLULAR UPTAKE; PHOSPHOROTHIOATE OLIGONUCLEOTIDES; INTRACELLULAR TRAFFICKING; TARGETED DELIVERY; LUMBAR PUNCTURE; SIRNA DELIVERY; SHAM CONTROL;

D O I：

10.3349/ymj.2020.61.4273

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

The reduction of survival motor neuron (SMN) protein causes spinal muscular atrophy (SMA), an autosomal recessive neuromuscular disease. Nusinersen is an antisense oligonucleotide, approved by the FDA, which specifically binds to the repressor within SMN2 exon 7 to enhance exon 7 inclusion and augment production of functional SMN protein. Nusinersen is the first new oligonudeotide-based drug targeting the central nervous system for the treatment of SMA. This review of nusinersen will discuss its action mechanism, cellular uptake, trafficking mechanisms, and administration approaches to cross the blood-brain barrier. Furthermore, nusinersen clinical trials will be assessed in terms of pharmacokinetics, tolerability and safety, the clinical outcomes of multiple intrathecal doses, and a discussion on the primary and secondary endpoints.

引用

页码：273 / 283

页数：11

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