Department of Function, ShiJiaZhuang Traditional Chinese Medical Hospital, ShiJiaZhuang, HeBei, China.
Yonsei Med J. 2020 Apr;61(4):273-283. doi: 10.3349/ymj.2020.61.4.273.
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 oligonucleotide-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.
运动神经元存活（SMN）蛋白减少导致脊髓性肌萎缩症（SMA），这是一种常染色体隐性神经肌肉疾病。nusinersen 是一种反义寡核苷酸药物，已获 FDA 批准，其特异性结合 SMN2 外显子 7 中的抑制物，从而增强外显子 7 的包含，并增加功能性 SMN 蛋白的产生。nusinersen 是第一个针对中枢神经系统治疗 SMA 的新型基于寡核苷酸的药物。本文将对 nusinersen 的作用机制、细胞摄取、转运机制和穿越血脑屏障的给药途径进行综述。此外，还将从药代动力学、耐受性和安全性、多次鞘内给药的临床结果以及对主要和次要终点的讨论等方面评估 nusinersen 的临床试验。
