Experience with nusinersen as a pathogenetic therapy in adult patients with spinal muscular atrophy 5q in the Republic of Bashkortostan

Background. Spinal muscular atrophy (SMA) affects 1 in 11,000 people. Until 2016, this was considered an incurable disease, but after the approval of nusinersen, the situation has changed. The efficacy of nusinersen therapy is also known in adult patients, although research is limited due to the majority of studies in infants and children. Nusinersen has been included in the list of “Vital and Essential Medicines” since 2021.

Aim. To analyze the experience of using nusinersen as a pathogenetic therapy for patients over 18 years of age with SMA 5q in the Republic of Bashkortostan.

Materials and methods. We examined eight patients receiving pathogenetic therapy with nusinersen (SMA type 2 – 34.5 %, SMA type 3 – 65.5 %). The Hammersmith Functional Motor Scale Expanded (HFMSE) and the Revised Upper Limb Module (RULM) were used for evaluating the effectiveness of therapy.

Results. The median increase on the HFMSE scale was +2 points (7.5, with the initial 5.5) and on the RULM scale – +4.5 points (17 points, with the initial 12.5). Clinically, this was expressed in an increase in muscle strength, an increase in daily activity; a decrease in bulbar, respiratory and vegetative disorders can also be noted. Subjectively, positive dynamics was noted in the increase in working capacity, improvement of the emotional background.

Conclusion. The use of the drug nusinersen in adult patients with SMA 5q in some cases provides clinical improvement. The presence of an “overall response” is defined as clinically significant change in one assessed measure of motor function. 

1. Mercuri E., Bertini E., Iannaccone S.T. Childhood spinal muscular atrophy: controversies and challenges. Lancet Neurol 2012;11(5):443–52. DOI: 10.1016/S1474-4422(12)70061-3

2. Sansone V.A., Coratti G., Pera M.C. et al. Sometimes they come back: new and old spinal muscular atrophy adults in the era of nusinersen. Eur J Neurol 2021;28(2):602–8. DOI: 10.1111/ene.14567

3. Lefebvre S., Bürglen L, Reboullet S. et al. Identification and characterization of a spinal muscular atrophy-determining gene. Cell 1995;80(1):155–65. DOI: 10.1016/0092-8674(95)90460-3

4. D'Amico A., Mercuri E., Tiziano F.D., Bertini E. Spinal muscular atrophy. Orphanet J Rare Dis 2011;6:71. DOI: 10.1186/1750-1172-6-71

5. Park J.M., Min Y.S., Park D., Park J.S. Effect of nusinersen in a late onset spinal muscular atrophy patient for 14 months: A case report. Medicine (Baltimore) 2021;100(1):e24236. DOI: 10.1097/MD.0000000000024236

6. Finkel R.S., Mercuri E., Darras B.T. et al. Nusinersen versus sham control in infantile-onset spinal muscular atrophy. N Engl J Med 2017;377(18):1723–32. DOI: 10.1056/NEJMoa1702752

7. Mercuri E., Darras B.T., Chiriboga C.A. et al. Nusinersen versus sham control in later-onset spinal muscular atrophy. N Engl J Med 2018;378(7):625–35. DOI: 10.1056/NEJMoa1710504

8. Chiriboga C.A., Swoboda K.J., Darras B.T. et al. Results from a phase 1 study of nusinersen (ISIS-SMN(Rx)) in children with spinal muscular atrophy. Neurology 2016;86(10):890–7. DOI: 10.1212/WNL.0000000000002445

9. Finkel R.S., Chiriboga C.A., Vajsar J. et al. Treatment of infantileonset spinal muscular atrophy with nusinersen: a phase 2, openlabel, dose-escalation study. Lancet 2016;388(10063):3017–26. DOI: 10.1016/S0140-6736(16)31408-8

10. Coratti G., Cutrona C., Pera M.C. et al. Motor function in type 2 and 3 SMA patients treated with nusinersen: a critical review and meta-analysis. Orphanet J Rare Dis 2021;16(1):430. DOI: 10.1186/s13023-021-02065-z

11. Freigang M., Wurster C.D., Hagenacker T. et al. Serum creatine kinase and creatinine in adult spinal muscular atrophy under nusinersen treatment. Ann Clin Transl Neurol 2021;8(5):1049–63. DOI: 10.1002/acn3.51340

12. Stolte B., Nonnemacher M., Kizina K. al. Nusinersen treatment in adult patients with spinal muscular atrophy: a safety analysis of laboratory parameters. J Neurol 2021;268(12):4667–79. DOI: 10.1007/s00415-021-10569-8

13. Hagenacker T., Wurster C.D., Günther R. et al. Nusinersen in adults with 5q spinal muscular atrophy: a non-interventional, multicentre, observational cohort study. Lancet Neurol 2020;19(4):317–25. DOI: 10.1016/S1474-4422(20)30037-5

14. Maggi L., Bello L., Bonanno S. et al. Nusinersen safety and effects on motor function in adult spinal muscular atrophy type 2 and 3. J Neurol Neurosurg Psychiatry 2020;91(11):1166–74. DOI: 10.1136/jnnp-2020-323822

15. Stolte B., Totzeck A., Kizina K. al. Feasibility and safety of intrathecal treatment with nusinersen in adult patients with spinal muscular atrophy. Ther Adv Neurol Dis 2018;11;175628641880324. DOI: 10.1177/1756286418803246

16. Walter M.C., Wenninger S., Thiele S. et al. Safety and treatment effects of nusinersen in longstanding adult 5q-SMA type 3 – a prospective observational study. J Neuromuscul Dis 2019;6(4):453–65. DOI: 10.3233/JND-190416

17. Wurster C.D., Winter B., Wollinsky K. et al. Intrathecal administration of nusinersen in adolescent and adult SMA type 2 and 3 patients. J Neurol 2019;266(1):183–94. DOI: 10.1007/s00415-018-9124-0

18. Yeo C.J.J., Simeone S.D., Townsend E.L. et al. Prospective cohort study of nusinersen treatment in adults with spinal muscular atrophy. J Neuromuscul Dis 2020;7(3):257–68. DOI: 10.3233/JND-190453

19. Schneider C., Wassermann M.K., Grether N.B. et al. Motor unit number estimation in adult patients with spinal muscular atrophy treated with nusinersen. Eur J Neurol 2021;28(9):3022–9. DOI: 10.1111/ene.15005

20. Darras B.T., Farrar M.A., Mercuri E. et al. An integrated safety analysis of infants and children with symptomatic spinal muscular atrophy (SMA) treated with nusinersen in seven clinical trials. CNS Drugs 2019;33(9):919–32. DOI: 10.1007/s40263-019-00656-w

21. Szabó L., Gergely A., Jakus R. et al. Efficacy of nusinersen in type 1, 2 and 3 spinal muscular atrophy: Real world data from Hungarian patients. Eur J Paediatr Neurol 2020;27:37–42. DOI: 10.1016/j.ejpn.2020.05.002

22. Bennett C.F., Swayze E.E. RNA targeting therapeutics: molecular mechanisms of antisense oligonucleotides as a therapeutic platform. Ann Rev Pharmacol Toxicol 2010;50:259–93. DOI: 10.1146/annurev.pharmtox.010909.105654

23. State register of medicines. Available at: https://grls.rosminzdrav.ru/. (In Russ.)

24. Clinical guidelines for the treatment of the disease “Proximal spinal muscular atrophy 5q”. Available at: https://cr.minzdrav.gov.ru/recomend/593_2. (In Russ.)

25. Hammersmith Function Motor Function Scale Expanded (HFMSE). Available at: https://ormiz.ru/adm/files/janssen/HFMSE.pdf. (In Russ.)

26. Revised Upper Limb Motor Function Module (RULM) for use in SMA. Available at: https://ormiz.ru/adm/files/janssen/RULM.pdf. (In Russ.)

27. Moshe-Lilie O., Visser A., Chahin N. et al. Nusinersen in adult patients with spinal muscular atrophy: observations from a single center. Neurology 2020;95(4):413–6. DOI: 10.1212/WNL.0000000000009914

28. Milella G.,Introna A., D'Errico E. et al. Cerebrospinal fluid and clinical profiles in adult type 2–3 spinal muscular atrophy patients treated with nusinersen: an 18-month single-centre experience. Clin Drug Investig 2021;41(9):775–84. DOI: 10.1007/s40261-021-01071-0