Консенсус по концепции современной эффективной терапии мышечной дистрофии Дюшенна

Мышечная дистрофия Дюшенна – генетическое орфанное нервно‑мышечное заболевание, обусловленное мутацией гена DMD, кодирующего белок дистрофин. В результате развивающегося и прогрессирующего повреждения и атрофии мышц дети теряют способность ходить, у них развиваются респираторные и кардиологические нарушения. При условии ранней диагностики медицинская помощь, направленная на максимально продолжительное сохранение амбулаторности пациента, при терапии глюкокортикостероидами и реабилитационных мероприятиях для предупреждения сердечно‑легочных осложнений и остеопороза существенно меняет траекторию развития заболевания. Эффективность новых препаратов генной таргетной терапии миодистрофии Дюшенна, частично восстанавливающих синтез полноразмерного или редуцированного дистрофина, зависит от их своевременного и адекватного использования в сочетании с комплексной медицинской помощью, рекомендованной для данной нозологии.

1. Ryder S., Leadley R.M., Armstrong N. et al. The burden, epidemiology, costs and treatment for Duchenne muscular dystrophy: an evidence review. Orphanet J Rare Dis 2017;(12):79. DOI: 10.1186/s13023-017-0631-3

2. Birnkrant D.J., Bushby K., Bann C.M., Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and neuromuscular, rehabilitation, endocrine, and gastrointestinal and nutritional management. 2018. Lancet Neurol 2018;17(3):251–67. DOI: 10.1016/S1474-4422(18)30024-3

3. Koenig M., Hofman E.P., Bertelson C.J. et al. Complete cloning of the Duchenne muscular dystrophy (DMD) cDNA and preliminary genomic organization of the DMD gene in normal and afected individuals. Cell 1987;50:509–17. DOI: 10.1016/0092-8674(87)90504-6

4. Crisafulli S., Sultana J., Fontana A. et al. Global epidemiology of Duchenne muscular dystrophy: an updated systematic review and meta-analysis. Orphanet J Rare Dis 2020;15(1):141. DOI: 10.1186/s13023-020-01430-8

5. Romitti P.A., Da P., Zhu Y. et al. Prevalence of Duchenne and Becker muscular dystrophies in the United States. Pediatrics 2015;135(3):513–21. DOI: 10.1542/peds.2014-2044

6. Ricci G., Bello L., Torri F. et al. Therapeutic opportunities and clinical outcome measures in Duchenne muscular dystrophy. Neurol Sci 2022;1–9. DOI:10.1007/s10072-022-06085-w

7. Blake D.J., Weir A., Newey S.E., Davies K.E. Function and genetics of dystrophin and dystrophin-related proteins in muscle. Physiol Rev 2002;82:291–329. DOI: 10.1152/physrev.00028.2001

8. Doorenweerd N., Mahfouz A., van Putten M. et al. Timing and localization of human dystrophin isoform expression provide insights into the cognitive phenotype of Duchenne muscular dystrophy [published correction appears in Sci Rep 2018;8(1):4058]. Sci Rep 2017;7(1):12575. DOI: 10.1038/s41598-017-12981-5

9. Ferizovic N., Summers J., Ortiz de Zarate I.B. Prognostic indicators of disease progression in Duchenne muscular dystrophy: A literature review and evidence synthesis. PLoS One 2022;17(3):e0265879. DOI: 10.1371/journal.pone.0265879

10. Birnkrant D.J., Bushby K., Bann C.M. et al. Diagnosis and management of Duchenne muscular dystrophy, part 2: respiratory, cardiac, bone health, and orthopaedic management. Lancet Neurol 2018;S1474-4422(18)30025-5.

11. Bianchi M.L., Morandi L., Andreucci E. et al. Low bone density and bone metabolism alterations in Duchenne muscular dystrophy: response to calcium and vitamin D treatment. Osteoporos Int 2011;(22):529–39. DOI: 10.1007/s00198-010-1275-5

12. Bian Q., McAdam L., Grynpas M. et al. Increased rates of vitamin D insufficiency in boys with Duchenne muscular dystrophy despite higher vitamin D3 supplementation. Global Pediatric Health 2019;(6):1–7. DOI: 10.1177/2333794X19835661

13. Jansen M., van Alfen N., Geurts A.C.H. et al. Assisted bicycle training delays functional deterioration in boys with Duchenne muscular dystrophy: the randomized controlled trial “No use is disuse”. Neurorehabilit Neural Rep 2013;27(9):816–27. DOI: 10.1177/1545968313496326

14. D'Amico A., Catteruccia M., Baranello G. Diagnosis of Duchenne muscular dystrophy in Italy in the last decade: Critical issues and areas for improvements. Neuromuscul Disord 2017;27(5):447–51. DOI: 10.1016/j.nmd.2017.02.006

15. Gremiakova T.A., Gremiakova O.I., Sakbaeva G.E. et al. Duchenne Muscular dystrophy diagnostic gaps in primary medical chain. 17 International Congress on Neuromuscular Diseases, Brussels, July 5–9, 2022. Abstr. eP04.01.06.

16. Bladen C.L., Salgado D., Monges S. The TREAT-NMD DMD Global Database: Analysis of more than 7,000 Duchenne muscular dystrophy mutations. Hum Mut 2015;36(4):395–402. DOI: 10.1002/humu.22758

17. Ward L.M., Konji V., Ma J. The management of osteoporsois in children. Osteoporos Int 2016;27:2147–79. DOI: 10.1007/ s00198-016-3515-9

18. Bachrach L.K. Diagnosis and treatment of pediatric osteoporosis. Curr Opin Endocrinol Diabetes Obes 2014;21:454–60. DOI: 10.1097/MED.0000000000000106

19. Sbrocchi A.M., Rauch F., Jacob P. et al. The use of intravenous bisphosphonate therapy to treat vertebral fractures due to osteoporosis among boys with Duchenne muscular dystrophy. Osteoporos Int 2012;23:2703–11. DOI: 10.1007/s00198-012-1911-3

20. Gordon K.E., Dooley J.M., Sheppard K.M. et al. Impact of bisphosphonates on survival for patients with Duchenne muscular dystrophy. Pediatrics 2011;127:e353–358. DOI: 10.1542/peds.2010-1666

21. Пигарова Е.А., Поваляева А.А., Дзеранова Л.К., Рожинская Л.Я. Роль витамина D в профилактике и лечении остеопороза – новый взгляд на известную проблему. РМЖ. Медицинское обозрение 2019;10(II):102–6

22. Carmel A.S., Shieh A., Bang H., Bockman R.S. The 25(OH)D level needed to maintain a favorable bisphosphonate response is ≥33 ng/ml. Osteoporos Int 2012;23:2479–87. DOI: 10.1007/s00198-011-1868-7

23. Peris P., Martínez-Ferrer A., Monegal A. et al. 25 hydroxyvitamin D serum levels influence adequate response to bisphosphonate treatment in postmenopausal osteoporosis. Bone 2012; 51:54–8. DOI: 10.1016/j.bone.2012.03.026

24. Srivastava T., Dai H., Haney C.J. Serum 25-hydroxyvitamin D level and acute-phase reaction following initial intravenous bisphosphonate. J Bone Miner Res 2011;26:437–8. DOI: 10.1002/jbmr.290

25. Rosen C.J., Brown S. Severe hypocalcemia after intravenous bisphosphonate therapy in occult vitamin D deficiency. N Engl J Med 2003;348:1503, 1504. DOI: 10.1056/NEJM200304103481521

26. Bertoldo F., Pancheri S., Zenari S. et al. Serum 25-hydroxyvitamin D levels modulate the acute-phase response associated with the first nitrogen-containing bisphosphonate infusion. J Bone Miner Res 2010;25:447–54. DOI: 10.1359/jbmr.09

27. Marden J.R., Freimark J., Yao Z. Real-world outcomes of long-term prednisone and deflazacort use in patients with Duchenne muscular dystrophy: experience at a single, large care center. J Comp Eff Res 2020;9(3):177–89. DOI: 10.2217/cer-2019-017

28. McDonald C.M. Long-term benefits of glucocorticoids in Duchenne muscular dystrophy – a matter of function, quality of life, and death. Available at: https://pdf.sciencedirectassets.com.

29. Matthews E., Brassington R., Kuntzer T. et al. Corticosteroids for the treatment of Duchenne muscular dystrophy. Cochrane Database Syst Rev 2016;(5):CD003725. DOI: 10.1002/14651858.CD003725.pub4

30. Henricson E.K., Abresch R.T., Cnaan A. et al. The cooperative international neuromuscular research group Duchenne natural history study: Glucocorticoid treatment preserves clinically meaningful functional milestones and reduces rate of disease progression as measured by manual muscle testing and other commonly used clinical trial outcome measures. Muscle Nerve 2013;48(1):55–67. DOI: 10.1002/mus.23808

31. Schram G., Fournier A., Leduc H. et al. All-cause mortality and cardiovascular outcomes with prophylactic steroid therapy in Duchenne muscular dystrophy. J Am Coll Cardiol 2013;61(9):948–54. DOI: 10.1016/j.jacc.2012.12.008

32. Gloss D., Moxley R.T., Ashwal S., Oskoui M. Practice guideline update summary: Corticosteroid treatment of Duchenne muscular dystrophy: Report of the Guideline Development Subcommittee of the American Academy of Neurology. Neurology 2016;86(5):465–72. DOI: 10.1212/WNL.000000000000233

33. McDonald C.M., Henricson E.K., Abresch R.T. et al. The 6-minute walk test and other endpoints in Duchenne muscular dystrophy: longitudinal natural history observations over 48 weeks from a multicenter study. Muscle Nerve 2013;48(3):343–56. DOI: 10.1002/mus.23902

34. McDonald C.M., Sajeev G., Yao Z. et al. Deflazacort vs prednisone treatment for Duchenne muscular dystrophy: A meta-analysis of disease progression rates in recent multicenter clinical trials. Muscle Nerve 2020;61(1):26–35. DOI: 10.1002/mus.26736

35. Manzur A.Y., Kuntzer T., Pike M., Swan A. Glucocorticoid corticosteroids for Duchenne muscular dystrophy. Cochrane Database Syst Rev 2008;(1):CD003725. DOI: 10.1002/14651858.CD003725.pub3

36. Connolly A.M., Zaidman C.M., Golumbek P.T. Twice-weekly glucocorticosteroids in infants and young boys with Duchenne muscular dystrophy. Muscle Nerve 2019;59(6):650–7. DOI: 10.1002/mus.26441

37. Beenakker E.A., Fock J.M., Van Tol M.J. et al. Intermittent prednisone therapy in Duchenne muscular dystrophy: A randomized controlled trial. Arch Neurol 2005;62(1):128–32. DOI: 10.1001/archneur.62.1.128

38. Ricotti V., Ridout D. A., Scott E. et al. Long-term benefits and adverse effects of intermittent versus daily glucocorticoids in boys with Duchenne muscular dystrophy. J Neurol Neurosurg Psychiatry 2013;84(6):698–705. DOI: 10.1136/jnnp-2012-303902

39. Quattrocelli M., Zelikovich A. S., Jiang Z. et al. Pulsed glucocorticoids enhance dystrophic muscle performance through epigeneticmetabolic reprogramming. JCI Insight 2019;4(24):e132402. DOI: 10.1172/jci.insight.132402

40. Quattrocellia M., Zelikovicha A.S., Salamonea I.M. et al. Mechanisms and clinical applications of glucocorticoid steroids in muscular dystrophy. J Neuromusc Disord 2021;8:39–52. DOI: 10.3233/JND-200556

41. Ten Dam K., de Groot I. J., Noordam C. et al. Normal height and weight in a series of ambulant Duchenne muscular dystrophy patients using the 10 day on/10 day off prednisone regimen. Neuromuscul Disord 2012;22(6):500–4. DOI: 10.1016/j.nmd.2012.01.005

42. Crabtree N.J., Adams J.E., Padidela R. et al. Growth, bone health & ambulatory status of boys with DMD treated with daily vs. intermittent oral glucocorticoid regimen. Bone 2018;116:181–6. DOI: 10.1016/j.bone.2018.07.019

43. Biggara W.D., Skalskyb A., McDonalds C.M. Comparing deflazacort and prednisone in Duchenne muscular dystrophy. J Neuromuscular Dis 2022;9:463–76. DOI 10.3233/JND-210776

44. Griggs R.C., Miller J.P., Greenberg C.R. et al. Efficacy and safety of deflazacort vs. prednisone and placebo for Duchenne muscular dystrophy. Neurology 2016;87(20):2123–31. DOI: 10.1212/WNL.0000000000003217

45. Kim S., Campbell K.A., Fox D.J. et al. STARnet. Corticosteroid treatments in males with Duchenne muscular dystrophy: Treatment duration and time to loss of ambulation. J Child Neurol 2015;30(10):1275–80. DOI: 10.1177/0883073814558120

46. Shieh P.B., McIntosh J., Jin F. et al. Deflazacort versus prednisone/ prednisolone for maintaining motor function and delaying loss of ambulation: A post HOC analysis from the ACT DMD trial. Muscle Nerve 2018;58(5):639–45. DOI: 10.1002/mus.26191

47. Barber B.J., Andrews J.G., Lu Z. et al. Oral corticosteroids and onset of cardiomyopathy in Duchenne muscular dystrophy. J Pediatr 2013;163(4):1080–4.e1. DOI: 10.1016/j.jpeds.2013.05.060

48. Sanchez M.J., Scott W., Pessana F. et al. Comparison of the effect of three steroid regimens on cardiac function in Duchenne muscular dystrophy. Pediatr Cardiol 2005;26(6):768–71. DOI: 10.1007/s00246-005-0909-4

49. Frank D.E., Schnell F.J., Akana C. et al. Increased dystrophin production with golodirsen in patients with Duchenne muscular dystrophy. Neurology 2020;94:e2270–e2282. DOI: 10.1212/WNL.0000000000009233

50. Mercuri E., Muntoni F., Osorio A.N.J. et al. Safety and effectiveness of ataluren: comparison of results from the STRIDE Registry and CINRG DMD Natural History Study. Comp Eff Res 2020;9(5):341–60. DOI: 10.2217/cer-2019-0171

51. Clemens P.R., Rao V.K., Connolly A.M. et al. Safety, tolerability, and efficacy of viltolarsen in boys with Duchenne muscular dystrophy amenable to exon 53 skipping a phase 2 randomized clinical trial. JAMA Neurol 2020;77(8):982–91. DOI: 10.1001/jamaneurol.2020.1264

52. Campbell C., Barohn R.J., Bertini E. Meta-analyses of ataluren randomized controlled trials in nonsense mutation Duchenne muscular dystrophy. J Comp Eff Res 2020;9(14):973–84. DOI: 10.2217/cer-2020-0095

53. Servais L., Mercuri E., Straub V. et al. Long-term safety and efficacy data of golodirsen in ambulatory patients with Duchenne muscular dystrophy amenable to exon 53 skipping: a first-in-human, multicenter, two-part, open-label, phase 1/2 trial. Nucleic Acid Ther 2022;32(1):29–39. DOI: 10.1089/nat.2021.0043

54. Rivera S.R., Jhamb S.K., Abdel-Hamid H.Z. et al. Medical management of muscle weakness in Duchenne muscular dystrophy. PLoS One 2020;15(10):e0240687. DOI: 10.1371/journal.pone.0240687

55. Mendell J.R., Goemans N., Lowes L.P. et al. Longitudinal effect of eteplirsen versus historical control on ambulation in Duchenne muscular dystrophy. Ann Neurol 2016;79(2):257–71. DOI: 10.1002/ana.24555

56. Гремякова Т.А., Артемьева С.Б., Вашакмадзе Н.Д. и др. Основополагающее значение понятий «амбулаторность» и «неам булаторность» в комплексной оценке состояния пациентов с мышечной дистрофией Дюшенна. Нервно-мышечные болезни 2022;12(2):10–8. DOI: 10.17650/2222-8721-2022-12-2-10-18 DOI: 10.17650/2222-8721-2022-12-2-10-18

57. Waldrop M.A., Flanigan K.M. Update in Duchenne and Becker muscular dystrophy. Curr Opin Neurol 2019;32(5):722–7. DOI: 10.1097/WCO.0000000000000739