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Drugs. 2017 Mar;77(4):473-479. doi: 10.1007/s40265-017-0711-7.
Spinal muscular atrophy (SMA) is a rare autosomal recessive disorder characterized by muscle atrophy and weakness resulting from motor neuron degeneration in the spinal cord and brainstem. It is most commonly caused by insufficient levels of survival motor neuron (SMN) protein (which is critical for motor neuron maintenance) secondary to deletions or mutations in the SMN1 gene. Nusinersen (SPINRAZA™) is a modified antisense oligonucleotide that binds to a specific sequence in the intron, downstream of exon 7 on the pre-messenger ribonucleic acid (pre-mRNA) of the SMN2 gene. This modulates the splicing of the SMN2 mRNA transcript to include exon 7, thereby increasing the production of full-length SMN protein. Nusinersen is approved in the USA for intrathecal use in paediatric and adult patients with SMA. Regulatory assessments for nusinersen as a treatment for SMA are underway in the EU and several other countries. This article summarizes the milestones in the development of nusinersen leading to this first approval for SMA in paediatric and adult patients.
脊髓性肌萎缩症（SMA）是一种罕见的常染色体隐性遗传病，其特征是由于脊髓和脑干中的运动神经元退化导致肌肉萎缩和无力。它最常见的原因是运动神经元存活（SMN）蛋白水平不足（这对于运动神经元的维持至关重要），这是由于 SMN1 基因的缺失或突变所致。Nusinersen（SPINRAZA™）是一种经过修饰的反义寡核苷酸，与 SMN2 基因前信使 RNA（pre-mRNA）上 7 号外显子下游的内含子中的特定序列结合。这调节了 SMN2 mRNA 转录本的剪接，包括 7 号外显子，从而增加全长 SMN 蛋白的产生。Nusinersen 在美国被批准用于鞘内注射治疗 SMA 的儿科和成年患者。在欧盟和其他几个国家，正在对 nusinersen 作为 SMA 治疗药物的监管评估进行中。本文总结了 nusinersen 开发过程中的重要里程碑，最终导致了儿科和成年 SMA 患者的首次批准。
