脊髓性肌萎缩症治疗研究进展

doi:10.7499/j.issn.1008-8830.2110041

摘要
图/表
参考文献(53)
相关文章 (5)
点击分布统计
下载分布统计

全文: PDF (562 KB) [HTML]
输出: BibTeX | EndNote (RIS) 背景资料

摘要脊髓性肌萎缩症（spinal muscular atrophy，SMA）是一种常染色体隐性遗传的神经肌肉疾病，主要特征为进行性肌无力和肌肉萎缩。该病是导致患儿在婴幼儿期死亡的首要遗传病。SMA治疗的研究领域近年来发展迅速，部分相关治疗药物已经成功获批上市。该文以SMA近年的治疗研究进展作一综述。

	服务

	把本文推荐给朋友
	加入我的书架
	加入引用管理器
	E-mail Alert
	RSS
	作者相关文章
	杨东铃

关键词 ：脊髓性肌萎缩症, 运动神经元存活基因, 基因治疗

Abstract：Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease characterized by progressive muscular weakness and atrophy. SMA, as an inherited disease, is the leading cause of death in infants and young children. Rapid progress has been made in the research field of SMA in recent years, and some related treatment drugs have been successfully approved for marketing. This article reviews the recent research advances in the treatment of SMA.

Key words： Spinal muscular atrophy Survival motor neuron gene Gene therapy

收稿日期: 2021-10-12

通讯作者: 阮毅燕，女，主任医师。Email：641039085@qq.com。 E-mail: 641039085@qq.com

作者简介: 杨东铃，女，硕士研究；

引用本文:

杨东铃. 脊髓性肌萎缩症治疗研究进展[J]. 中国当代儿科杂志, 2022, 24(2): 204-209.

YANG Dong-Ling. Recent research on the treatment of spinal muscular atrophy[J]. CJCP, 2022, 24(2): 204-209.

链接本文:

http://www.zgddek.com/CN/10.7499/j.issn.1008-8830.2110041 或 http://www.zgddek.com/CN/Y2022/V24/I2/204

	Lunn MR, Wang CH. Spinal muscular atrophy[J]. Lancet, 2008, 371(9630): 2120-2133. PMID: 18572081. DOI: 10.1016/S0140-6736(08)60921-6.
	Fang P, Li L, Zeng J, et al. Molecular characterization and copy number of SMN1, SMN2 and NAIP in Chinese patients with spinal muscular atrophy and unrelated healthy controls[J]. BMC Musculoskelet Disord, 2015, 16(1): 11. PMID: 25888055. PMCID: PMC4328246. DOI: 10.1186/s12891-015-0457-x.
	利婧, 朱瑜龄, 詹益鑫, 等. 78例脊肌萎缩症患者SMN1基因突变分析[J]. 中华医学遗传学杂志, 2017, 34(5): 658-661. PMID: 28981927. DOI: 10.3760/cma.j.issn.1003-9406.2017.05.008.
	Singh RN, Singh NN. Mechanism of splicing regulation of spinal muscular atrophy genes[J]. Adv Neurobiol, 2018, 20: 31-61. PMID: 29916015. PMCID: PMC6026014. DOI: 10.1007/978-3-319-89689-2_2.
	5 北京医学会医学遗传学分会, 北京罕见病诊疗与保障学会. 脊髓性肌萎缩症遗传学诊断专家共识[J]. 中华医学杂志, 2020, 100(40): 3130-3140. DOI: 10.3760/cma.j.cn112137-20200803-02267.
	Saraiva J, Nobre RJ, Pereira de Almeida L. Gene therapy for the CNS using AAVs: the impact of systemic delivery by AAV9[J]. J Control Release, 2016, 241: 94-109. PMID: 27637390. DOI: 10.1016/j.jconrel.2016.09.011.
	7 夏训明. 美国FDA批准Zolgensma(onasemnogene abeparvovec-xioi)治疗儿童脊髓性肌萎缩症[J]. 广东药科大学学报, 2019, 35(3): 332.
	Mendell JR, Al-Zaidy S, Shell R, et al. Single-dose gene-replacement therapy for spinal muscular atrophy[J]. N Engl J Med, 2017, 377(18): 1713-1722. PMID: 29091557. DOI: 10.1056/NEJMoa1706198.
	9 Day JW, Chiriboga CA, Crawford TO, et al. Onasemnogene abeparvovec gene-replacement therapy (GRT) for spinal muscular atrophy type 1 (SMA1): pivotal phase 3 study (STR1VE) update[J]. Neuropediatrics, 2019, 50(S02): S1-S55. DOI: 10.1055/s-0039-1698170.
	Mercuri E, Muntoni F, Baranello G, et al. Onasemnogene abeparvovec gene therapy for symptomatic infantile-onset spinal muscular atrophy type 1 (STR1VE-EU): an open-label, single-arm, multicentre, phase 3 trial[J]. Lancet Neurol, 2021, 20(10): 832-841. PMID: 34536405. DOI: 10.1016/S1474-4422(21)00251-9.
	11 Schultz M, Swoboda KJ, Farrar M, et al. Onasemnogene abeparvovec gene-replacement therapy (GRT) in pre-symptomatic spinal muscular atrophy (SMA): SPR1NT study update[J]. Neuropediatrics, 2019, 50(S02): S1-S55. DOI: 10.1055/s-0039-1698169.
	12 U.S. Food and Drug Administration. ZOLGENSMA[EB/OL]. (2019-05-24)[2021-09-18]. https://www.fda.gov/vaccines-blood-biologics/zolgensma.
	13 Novartis AG. Novartis announces AVXS-101 intrathecal study update[EB/OL]. (2019-10-30)[2021-09-18]. https://www.novartis.com/news/media-releases/novartis-announces-avxs-101-intrathecal-study-update.
	Hoy SM. Onasemnogene abeparvovec: first global approval[J]. Drugs, 2019, 79(11): 1255-1262. PMID: 31270752. DOI: 10.1007/s40265-019-01162-5.
	Hua YM, Sahashi K, Hung G, et al. Antisense correction of SMN2 splicing in the CNS rescues necrosis in a type III SMA mouse model[J]. Genes Dev, 2010, 24(15): 1634-1644. PMID: 20624852. PMCID: PMC2912561. DOI: 10.1101/gad.1941310.
	16 杨君义. 一种治疗脊髓性肌萎缩症的新药: nusinersen[J]. 中国新药与临床杂志, 2018, 37(5): 259-261. DOI: 10.14109/j.cnki.xyylc.2018.05.003.
	17 渤健生物. 全球首个脊髓性肌萎缩症治疗药物诺西那生钠注射液正式在中国上市, 中国脊髓性肌萎缩症诊治中心联盟成立[EB/OL]. (2019-04-28)[2021-09-19]. https://mp.weixin.qq.com/s/xsTn0kEqUjwCbWN9csZA1g.
	Finkel RS, Chiriboga CA, Vajsar J, et al. Treatment of infantile-onset spinal muscular atrophy with nusinersen: a phase 2, open-label, dose-escalation study[J]. Lancet, 2016, 388(10063): 3017-3026. PMID: 27939059. DOI: 10.1016/S0140-6736(16)31408-8.
	Finkel RS, Mercuri E, Darras BT, et al. Nusinersen versus sham control in infantile-onset spinal muscular atrophy[J]. N Engl J Med, 2017, 377(18): 1723-1732. PMID: 29091570. DOI: 10.1056/NEJMoa1702752.
	De Vivo DC, Bertini E, Swoboda KJ, et al. Nusinersen initiated in infants during the presymptomatic stage of spinal muscular atrophy: interim efficacy and safety results from the phase 2 NURTURE study[J]. Neuromuscul Disord, 2019, 29(11): 842-856. PMID: 31704158. PMCID: PMC7127286. DOI: 10.1016/j.nmd.2019.09.007.
	21 Kirschner J, Darras BT, Farrar MA, et al. Interim report on the safety and efficacy of longer-term treatment with nusinersen in later-onset spinal muscular atrophy (SMA): Results from the SHINE study[J]. Neuromuscul Dis, 2019, 29(Supple 1): S184. DOI: 10.1016/j.nmd.2019.06.514.
	Hoy SM. Nusinersen: first global approval[J]. Drugs, 2017, 77(4): 473-479. PMID: 28229309. DOI: 10.1007/s40265-017-0711-7.
	Sivaramakrishnan M, McCarthy KD, Campagne S, et al. Binding to SMN2 pre-mRNA-protein complex elicits specificity for small molecule splicing modifiers[J]. Nat Commun, 2017, 8(1): 1476. PMID: 29133793. PMCID: PMC5684323. DOI: 10.1038/s41467-017-01559-4.
	Dhillon S. Risdiplam: first approval[J]. Drugs, 2020, 80(17): 1853-1858. PMID: 33044711. DOI: 10.1007/s40265-020-01410-z.
	25 国家药品监督管理局. 国家药品监督管理局批准利司扑兰口服溶液用散上市[EB/OL]. (2021-06-17)[2021-09-21]. https://www.nmpa.gov.cn/yaowen/ypjgyw/20210617084152178.html.
	26 Baranello G, Servais L, Day J, et al. FIREFISH part 1: 16-month safety and exploratory outcomes of risdiplam (RG7916) treatment in infants with type 1 spinal muscular atrophy[J]. Neuromuscul Disord, 2019, 29(S1): S184. DOI: 10.1016/j.nmd.2019.06.515.
	27 Darras BT, Masson R, Mazurkiewicz-Bedzińska M, et al. FIREFISH part 2: 24-month efficacy and safety of risdiplam in infants with type 1 spinal muscular atrophy (SMA)[J]. Neuropediatrics, 2021, 52(S01): S1-S53. DOI: 10.1055/s-0041-1739636.
	28 Mercuri E, Baranello G, Kirschner J, et al. Sunfish part 1: 18-month safety and exploratory outcomes of risdiplam (RG7916) treatment in patients with type 2 or 3 spinal muscular atrophy[J]. Neuromuscul Disord, 2019, 29(S1): S208. DOI: 10.1016/j.nmd.2019.06.595.
	29 Chiriboga C, Mercuri E, Fischer D, et al. JEWELFISH: safety and pharmacodynamic data in patients with spinal muscular atrophy (SMA) receiving treatment with risdiplam (RG7916) that have previously been treated with nusinersen[J]. Neuromuscul Disord, 2019, 29(S1): S187. DOI: 10.1016/j.nmd.2019.06.525.
	30 Bertini E, Day J, Muhaizea M, et al. RAINBOWFISH: a study of risdiplam (RG7916) in newborns with pre-symptomatic spinal muscular atrophy (SMA)[J]. Neuromuscul Disord, 2019, 29(S1): S187. DOI: 10.1016/j.nmd.2019.06.524.
	31 U.S. Food and Drug Administration. Drug trials snapshots: EVRYSDI[EB/OL]. (2020-08-18)[2021-09-25]. https://www.fda.gov/drugs/drug-approvals-and-databases/drug-trials-snapshots-evrysdi.
	Calder AN, Androphy EJ, Hodgetts KJ. Small molecules in development for the treatment of spinal muscular atrophy[J]. J Med Chem, 2016, 59(22): 10067-10083. PMID: 27490705. PMCID: PMC5744254. DOI: 10.1021/acs.jmedchem.6b00670.
	33 Peters T, Jevtic S, Carr D, et al. Serum neurofilament light chain in type 1 spinal muscular atrophy: second part of a branaplam phase II study[J]. Neuromuscul Dis, 29(Supple 1): S147. DOI: 10.1016/j.nmd.2019.06.388.
	Chen TH. New and developing therapies in spinal muscular atrophy: from genotype to phenotype to treatment and where do we stand?[J]. Int J Mol Sci, 2020, 21(9): 3297. PMID: 32392694. PMCID: PMC7246502. DOI: 10.3390/ijms21093297.
	Qu YJ, Ge XS, Bai JL, et al. Association of copy numbers of survival motor neuron gene 2 and neuronal apoptosis inhibitory protein gene with the natural history in a Chinese spinal muscular atrophy cohort[J]. J Child Neurol, 2015, 30(4): 429-436. PMID: 25330799. DOI: 10.1177/0883073814553271.
	Ahmad S, Wang Y, Shaik GM, et al. The zinc finger protein ZPR1 is a potential modifier of spinal muscular atrophy[J]. Hum Mol Genet, 2012, 21(12): 2745-2758. PMID: 22422766. PMCID: PMC3363332. DOI: 10.1093/hmg/dds102.
	Oprea GE, Kr?ber S, McWhorter ML, et al. Plastin 3 is a protective modifier of autosomal recessive spinal muscular atrophy[J]. Science, 2008, 320(5875): 524-527. PMID: 18440926. PMCID: PMC4908855. DOI: 10.1126/science.1155085.
	Ackermann B, Kr?ber S, Torres-Benito L, et al. Plastin 3 ameliorates spinal muscular atrophy via delayed axon pruning and improves neuromuscular junction functionality[J]. Hum Mol Genet, 2013, 22(7): 1328-1347. PMID: 23263861. DOI: 10.1093/hmg/dds540.
	Torres-Benito L, Schneider S, Rombo R, et al. NCALD antisense oligonucleotide therapy in addition to nusinersen further ameliorates spinal muscular atrophy in mice[J]. Am J Hum Genet, 2019, 105(1): 221-230. PMID: 31230718. PMCID: PMC6612520. DOI: 10.1016/j.ajhg.2019.05.008.
	Hammond SM, Hazell G, Shabanpoor F, et al. Systemic peptide-mediated oligonucleotide therapy improves long-term survival in spinal muscular atrophy[J]. Proc Natl Acad Sci U S A, 2016, 113(39): 10962-10967. PMID: 27621445. PMCID: PMC5047168. DOI: 10.1073/pnas.1605731113.
	Weber JJ, Clemensson LE, Schi?th HB, et al. Olesoxime in neurodegenerative diseases: scrutinising a promising drug candidate[J]. Biochem Pharmacol, 2019, 168: 305-318. PMID: 31283931. DOI: 10.1016/j.bcp.2019.07.002.
	Sumner CJ, Huynh TN, Markowitz JA, et al. Valproic acid increases SMN levels in spinal muscular atrophy patient cells[J]. Ann Neurol, 2003, 54(5): 647-654. PMID: 14595654. DOI: 10.1002/ana.10743.
	Biondi O, Branchu J, Ben Salah A, et al. IGF-1R reduction triggers neuroprotective signaling pathways in spinal muscular atrophy mice[J]. J Neurosci, 2015, 35(34): 12063-12079. PMID: 26311784. PMCID: PMC6705454. DOI: 10.1523/JNEUROSCI.0608-15.2015.
	Rudnicki SA, Andrews JA, Duong T, et al. Reldesemtiv in patients with spinal muscular atrophy: a phase 2 hypothesis-generating study[J]. Neurotherapeutics, 2021, 18(2): 1127-1136. PMID: 33624184. PMCID: PMC8423982. DOI: 10.1007/s13311-020-01004-3.
	Barrett D, Bilic S, Chyung Y, et al. A randomized phase 1 safety, pharmacokinetic and pharmacodynamic study of the novel myostatin inhibitor apitegromab (SRK-015): a potential treatment for spinal muscular atrophy[J]. Adv Ther, 2021, 38(6): 3203-3222. PMID: 33963971. PMCID: PMC8189951. DOI: 10.1007/s12325-021-01757-z.
	Stam M, Wadman RI, Wijngaarde CA, et al. Protocol for a phase II, monocentre, double-blind, placebo-controlled, cross-over trial to assess efficacy of pyridostigmine in patients with spinal muscular atrophy types 2-4 (SPACE trial)[J]. BMJ Open, 2018, 8(7): e019932. PMID: 30061431. PMCID: PMC6067401. DOI: 10.1136/bmjopen-2017-019932.
	Corti S, Nizzardo M, Nardini M, et al. Embryonic stem cell-derived neural stem cells improve spinal muscular atrophy phenotype in mice[J]. Brain, 2010, 133(Pt 2): 465-481. PMID: 20032086. DOI: 10.1093/brain/awp318.
	Shaw SW, Peng SY, Liang CC, et al. Prenatal transplantation of human amniotic fluid stem cell could improve clinical outcome of type III spinal muscular atrophy in mice[J]. Sci Rep, 2021, 11(1): 9158. PMID: 33911155. PMCID: PMC8080644. DOI: 10.1038/s41598-021-88559-z.
	49 北京医学会罕见病分会, 北京医学会医学遗传学分会, 北京医学会神经病学分会神经肌肉病学组, 等. 脊髓性肌萎缩症多学科管理专家共识[J]. 中华医学杂志, 2019, 99(19): 1460-1467. DOI: 10.3760/cma.j.issn.0376-2491.2019.19.006.
	Ropars J, Peudenier S, Genot A, et al. Multidisciplinary approach and psychosocial management of spinal muscular atrophy (SMA)[J]. Arch Pediatr, 2020, 27(7S): 7S45-7S49. PMID: 33357598. DOI: 10.1016/S0929-693X(20)30277-3.
	Oechsel KF, Cartwright MS. Combination therapy with onasemnogene and risdiplam in spinal muscular atrophy type 1[J]. Muscle Nerve, 2021, 64(4): 487-490. PMID: 34287987. DOI: 10.1002/mus.27375.
	Harada Y, Rao VK, Arya K, et al. Combination molecular therapies for type 1 spinal muscular atrophy[J]. Muscle Nerve, 2020, 62(4): 550-554. PMID: 32710634. DOI: 10.1002/mus.27034.
	Farrelly-Rosch A, Lau CL, Patil N, et al. Combination of valproic acid and morpholino splice-switching oligonucleotide produces improved outcomes in spinal muscular atrophy patient-derived fibroblasts[J]. Neurochem Int, 2017, 108: 213-221. PMID: 28389270. DOI: 10.1016/j.neuint.2017.02.016.