Ionis Pharmaceuticals, Carlsbad, California 92010, USA; email:
Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
Annu Rev Neurosci. 2019 Jul 8;42:385-406. doi: 10.1146/annurev-neuro-070918-050501.
Antisense oligonucleotides represent a novel therapeutic platform for the discovery of medicines that have the potential to treat most neurodegenerative diseases. Antisense drugs are currently in development for the treatment of amyotrophic lateral sclerosis, Huntington's disease, and Alzheimer's disease, and multiple research programs are underway for additional neurodegenerative diseases. One antisense drug, nusinersen, has been approved for the treatment of spinal muscular atrophy. Importantly, nusinersen improves disease symptoms when administered to symptomatic patients rather than just slowing the progression of the disease. In addition to the benefit to spinal muscular atrophy patients, there are discoveries from nusinersen that can be applied to other neurological diseases, including method of delivery, doses, tolerability of intrathecally delivered antisense drugs, and the biodistribution of intrathecal dosed antisense drugs. Based in part on the early success of nusinersen, antisense drugs hold great promise as a therapeutic platform for the treatment of neurological diseases.
反义寡核苷酸是一种新的治疗平台，可用于发现有潜力治疗大多数神经退行性疾病的药物。目前正在开发用于治疗肌萎缩侧索硬化症、亨廷顿病和阿尔茨海默病的反义药物，并且还有多个研究项目正在进行中，以针对其他神经退行性疾病。一种反义药物 nusinersen 已被批准用于治疗脊髓性肌萎缩症。重要的是，nusinersen 在给予有症状的患者时可以改善疾病症状，而不仅仅是减缓疾病的进展。除了对脊髓性肌萎缩症患者的益处外，nusinersen 还有一些发现可以应用于其他神经疾病，包括给药方法、剂量、鞘内给予反义药物的耐受性以及鞘内给予反义药物的生物分布。部分基于 nusinersen 的早期成功，反义药物作为治疗神经疾病的治疗平台具有很大的前景。
