Spinal muscular atrophy type 1: current status of the issue

Abstract

The development of medical technologies has led to an increase in the survival of patients with spinal muscular atrophy (SMA). In turn, these drugs have a high cost, which limits their availability for children with SMA. This fact posed new challenges for the science community. Currently, clinical trials of the effectiveness of drugs for the treatment of various types of spinal muscular atrophy are underway. Clinical forms of SMA are grouped into 5 subtypes depending on the severity of the disease and the age of onset of the disease. Type 1 spinal muscular atrophy, or Werdnig-Hoffmann disease, is the most common, accounting for 60% of all cases of the disease. The first positive results of clinical trials of two potentially new and effective drugs − Zolgensma and Risdiplam were published recently. Despite this, the inaccessibility of treatment of spinal muscular atrophy creates a serious interdisciplinary problem at the state level, including medical and social rehabilitation, which is important to understand when planning medical care.

Keywords

SMA / spinal muscular atrophy / treatment / diagnosis / medical and social rehabilitation / Spinraza / Zolgensma / Risdiplam

References

[1] Dangouloff T, Servais L. Clinical evidence supporting early treatment in spinal muscular atrophy: current perspectives. Ther Clin Risk Manag. 2019;15:1153-1161. https://doi.org/10.2147/TCRM.S172291.

[2] Darras BT. Spinal muscular atrophies. Pediatr Clin North Am. 2015;62(3):743-766. https://doi.org/10.1016/j.pcl.2015.03.010.

[3] Farrar MA, Kiernan MC. The genetics of spinal muscular atrophy: progress and challenges. Neurotherapeutics. 2014;12(2):290-302. https://doi.org/10.1007/s13311-014-0314-x.

[4] Verhaart IE, Robertson A, Wilson IJ, et al. Prevalence, incidence and carrier frequency of 5q-linked spinal muscular atrophya literature review. Orphanet J Rare Dis. 2017;12(1):124. https://doi.org/10.1186/s13023-017-0671-8.

[5] Rao VK, Kapp D, Schroth M. Gene therapy for spinal muscular atrophy: an emerging treatment option for a devastating disease. J Manage Care Spec Pharm. 2018;24(12a Suppl):3-16. https://doi.org/10.18553/jmcp.2018.24.12-a.s3.

[6] Селиверстов Ю.А., Клюшников С.А., Иллариошкин С.Н. Спинальные мышечные атрофии: понятие, дифференциальная диагностика, перспективы лечения // Нервные болезни. ― 2015. ― №3. ― С. 9−17. [Seliverstov YuA, Klyushnikov SA, Illarioshkin SN. Spinal’nye myshechnye atrofii: ponyatie, differentsial’naya diagnostika, perspektivy lecheniya. Nervnye bolezni. 2015;(3):9-17. (In Russ.)]

[7] Kolb SJ, Kissel JT. Spinal muscular atrophy. Neurol Clin. 2015;33(4):831-846. https://doi.org/10.1016/j.ncl.2015.07.004.

[8] Finkel RS, McDermott MP, Kaufmann P, et al. Observational study of spinal muscular atrophy type I and implications for clinical trials. Neurology. 2014;83(9):810-817. https://doi.org/10.1212/WNL.0000000000000741.

[9] Thomas NH, Dubowitz V. The natural history of type I (severe) spinal muscular atrophy. Neuromuscul Disord. 1994;4(5-6):497-502. https://doi.org/10.1016/0960-8966(94)90090-6.

[10] Zerres K, Rudnik-Schoneborn S. Natural history in proximal spinal muscular atrophy. Clinical analysis of 445 patients and suggestions for a modification of existing classifications. Arch Neurol. 1995;52(5):518-523. https://doi.org/10.1001/archneur.1995.00540290108025.

[11] Mercuri E, Finkel RS, Muntoni F, et al.; SMA Care Group. Diagnosis and management of spinal muscular atrophy: part 1: recommendations for diagnosis, rehabilitation, orthopedic and nutritional care. Neuromuscul Disord. 2018;28(2):103-115. https://doi.org/10.1016/j.nmd.2017.11.005.

[12] Cuscó I, Barceló MJ, Rojas-García R, et al. SMN2 copy number predicts acute or chronic spinal muscular atrophy but does not account for intrafamilial variability in siblings. J Neurol. 2006;253:21-25. https://doi.org/10.1007/s00415-005-0912-y.

[13] Prior TW, Krainer AR, Hua Y, et al. A positive modifier of spinal muscular atrophy in the SMN2 gene. Am J Hum Genet. 2009;85(3):408-413. https://doi.org/10.1016/j.ajhg.2009.08.002.

[14] Wang CH, Finkel RS, Bertini ES, et al. Consensus statement for standard of care in spinal muscular atrophy. J Child Neurol. 2007;22(8):1027-1049. https://doi.org/10.1177/0883073807305788.

[15] Schorling DC, Pechmann A, Kirschner J. Advances in treatment of spinal muscular atrophy—new phenotypes, new challenges, new implications for care. J Neuromuscul Dis. 2020;7(1):1-13. https://doi.org/10.3233/JND-190424.

[16] Finkel RS, Mercuri E, Meyer OH, et al. Diagnosis and management of spinal muscular atrophy: Part 2: Pulmonary and acute caremedications, supplements and immunizations; other organ systems; and ethics. Neuromuscul Disord. 2018;28(3):197-207. https://doi.org/10.1016/j.nmd.2017.11.004.

[17] Lefebvre S, Burlet P, Liu Q, et al. Correlation between severity and SMN protein level in spinal muscular atrophy. Nat Genet. 1997;16(3):265-269. https://doi.org/10.1038/ng0797-265.

[18] Hua Y, Sahashi K, Hung G, et al. Antisense correction of SMN2 splicing in the CNS rescues necrosis in a type III SMA mouse model. Genes Dev. 2010;24(15):1634-1644. https://doi.org/10.1101/gad.1941310.

[19] Bennett CF, Baker BF, Pham N, et al. Pharmacology of antisense drugs. Annu Rev Pharmacol Toxicol. 2017;57:81-105. https://doi.org/10.1146/annurev-pharmtox-010716-104846.

[20] Li Q. Nusinersen as a therapeutic agent for spinal muscular atrophy. Yonsei Med J. 2020;61(4):273-283. https://doi.org/10.3349/ymj.2020.61.4.273.

[21] Клинические исследования и лекарства [интернет]. ― СМАСемьи, 2020. [SMAFamily. Clinical trials and treatment. (In Russ.)]. Доступно по: https://f-sma.ru/. Ссылка активна на 03.03.2020.

[22] Study of Nusinersen (BIIB058) in participants with spinal muscular atrophy (DEVOTE). ClinicalTrials.gov; 2020. Available at: https://clinicaltrials.gov/ct2/show/NCT04089566.

RIGHTS & PERMISSIONS

Eco-Vector