Department of neurology, Ghent University Hospital, Belgium, C.-Heymanslaan 10, 9000, Ghent, Belgium.
Acta Neurol Belg. 2019 Dec;119(4):523-533. doi: 10.1007/s13760-019-01199-z. Epub 2019 Aug 6.
Recent discovery of nusinersen, an antisense oligonucleotide drug, has provided encouragement for improving treatment of spinal muscular atrophy. No therapeutic options currently exist for this autosomal recessive motor neuron disorder. Nusinersen is developed for intrathecal use and binds to a specific sequence within the survival motor neuron 2 pre-messenger RNA, modifying the splicing process to promote expression of full-length survival motor neuron protein. We performed a MEDLINE and CENTRAL search to investigate the current evidence for treatment with nusinersen in patients with spinal muscular atrophy. Four papers were withheld, including two phase-3 randomized controlled trials, one phase-2 open-label clinical trial and one phase-1 open-label clinical trial. Outcome measures concerned improvement in motor function and milestones, as well as event-free survival and survival. Results of these trials are hopeful with significant and clinically meaningful improvement due to treatment with intrathecal nusinersen in patients with early- and later-onset spinal muscular atrophy, although this does not restore age-appropriate function. Intrathecal nusinersen has acceptable safety and tolerability. Further trials regarding long-term effects and safety aspects as well as trials including broader spinal muscular atrophy and age categories are required and ongoing.
最近发现的反义寡核苷酸药物 nusinersen，为改善脊髓性肌萎缩症的治疗提供了希望。这种常染色体隐性运动神经元疾病目前尚无治疗选择。Nusinersen 是为鞘内使用而开发的，它与生存运动神经元 2 前信使 RNA 中的特定序列结合，改变剪接过程，促进全长生存运动神经元蛋白的表达。我们进行了 MEDLINE 和 CENTRAL 检索，以调查目前使用 nusinersen 治疗脊髓性肌萎缩症患者的证据。有四篇论文被保留，包括两项 3 期随机对照试验、一项 2 期开放标签临床试验和一项 1 期开放标签临床试验。这些试验的结果令人鼓舞，鞘内注射 nusinersen 可显著改善运动功能和里程碑事件，以及无事件生存和生存。尽管这并不能恢复与年龄相适应的功能，但早期和晚期发病的脊髓性肌萎缩症患者接受鞘内 nusinersen 治疗后，确实有显著且具有临床意义的改善。鞘内 nusinersen 具有可接受的安全性和耐受性。需要并正在进行关于长期效果和安全性方面的进一步试验，以及包括更广泛的脊髓性肌萎缩症和年龄类别在内的试验。
