Consensus concept of modern effective therapy for Duchenne muscular dystrophy

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Abstract

Duchenne muscular dystrophy is a genetic orphan neuromuscular disease caused by a mutation in the DMD gene encoding the protein dystrophin. As a result of developing and progressive muscle damage and atrophy, children lose the ability to walk, develop respiratory and cardiac disorders. The core elements of good care standards are early diagnosis, prevention and treatment of osteoporosis, daily physical therapy, regular rehabilitation, glucocorticosteroids, and control of heart and lung function. The clinical effect of new targeted pathogenetic therapies for Duchenne muscular dystrophy, restoring synthesis of full or truncated dystrophin, depend on their appropriate combination with existing standards of care.

About the authors

T. A. Gremyakova

Charitable Foundation “Gordey”; Central Clinical Hospital with a Polyclinic of the President Administration

Email: tag@dmd-russia.ru

Tatyana Andreevna Gremyakova

29 Sokolovo-Meshcherskaya St., Moscow 125466

15 Marshala Timoshenko St., Moscow 121359

Russian Federation

S. B. Artemyeva

Yu. E. Veltishchev Research Clinical Institute of Pediatrics

Email: fake@neicon.ru

2 Taldomskaya St., Moscow 125412

Russian Federation

E. N. Baybarina

V. I. Kulakov Scientific Center for Obstetrics, Gynecology and Perinatology

Email: fake@neicon.ru

4 Akademika Oparina St., Moscow 117198

Russian Federation

N. D. Vashakmadze

Central Clinical Hospital of the Russian Academy of Sciences

Email: fake@neicon.ru

1A Litovskiy Bulvar, Moscow 117593

Russian Federation

V. I. Guzeva

Saint-Petersburg State Pediatric Medical University

Email: fake@neicon.ru

2 Litovskaya St., Saint Petersburg 194100

Russian Federation

E. V. Gusakova

Central State Medical Academy of the President Administration

Email: fake@neicon.ru

Build. 1A, 19 Marshala Timoshenko St., Moscow 121359

Russian Federation

L. M. Kuzenkova

National Medical Research Center for Children’s Health

Email: fake@neicon.ru

Build. 1, 2 Lomonosovskiy Prospect, Moscow 119991

Russian Federation

A. E. Lavrova

Volga Research Medical University, Institute of Pediatrics University Clinic

Email: fake@neicon.ru

22 Semachko St., Nizhny Novgorod 603155

Russian Federation

O. A. Lvova

Children’s City Hospital No. 9; Ural State University named after B. N. Yeltsin

Email: fake@neicon.ru

51 Reshetskaya St., Yekaterinburg 620050

19 Mira St., Yekaterinburg 620002

Russian Federation

S. V. Mikhaylova

Russian Children’s Clinical Hospital

Email: fake@neicon.ru

117 Leninskiy Prospekt, Moscow 119571

Russian Federation

L. P. Nazarenko

Research Institute of Medical Genetics, Tomsk National Research Medical Center

Email: fake@neicon.ru

10 Naberezhnaya reki Ushayki, Tomsk 634050

Russian Federation

S. S. Nikitin

N. P. Bochkov Medical Genetic Research Center

Email: fake@neicon.ru

1 Moskvorechye St., Moscow 115522

Russian Federation

A. V. Polyakov

N. P. Bochkov Medical Genetic Research Center

Email: fake@neicon.ru

1 Moskvorechye St., Moscow 115522

Russian Federation

E. L. Dadali

N. P. Bochkov Medical Genetic Research Center

Email: fake@neicon.ru

1 Moskvorechye St., Moscow 115522

Russian Federation

A. G. Rumyantsev

N. I. Pirogov Russian National Research Medical University of the Ministry of Health of Russia

Email: fake@neicon.ru

1 Ostrovityanova St., Moscow 117997

Russian Federation

G. E. Sakbaeva

Central Clinical Hospital with a Polyclinic of the President Administration

Email: fake@neicon.ru

15 Marshala Timoshenko St., Moscow 121359

Russian Federation

V. M. Suslov

Saint-Petersburg State Pediatric Medical University

Email: fake@neicon.ru

2 Litovskaya St., Saint Petersburg 194100

Russian Federation

O. I. Gremyakova

Charitable Foundation “Gordey”

Author for correspondence.
Email: fake@neicon.ru

29 Sokolovo-Meshcherskaya St., Moscow 125466

Russian Federation

A. A. Stepanov

Central Clinical Hospital with a Polyclinic of the President Administration

Email: fake@neicon.ru

15 Marshala Timoshenko St., Moscow 121359

Russian Federation

N. I. Shakhovskaya

Psycho-neurological Hospital for Children with CNS Lesions with Mental Disorders

Email: fake@neicon.ru

1 Ivana Susanina St., Moscow 127486

Russian Federation

References

  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. Pigarova E.A., Povalyaeva A.A., Dzeranova L.K., Rozhinskaya L.Ya. The role of vitamin D in the prevention and treatment of osteoporosis: novel insight into the known issue. RMJ. Medizinskoe obozrenie = Medical Review 2019;10(II):102–6. (In Russ.).
  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 dystro-phy 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. Gremyakova T.A., Artemyeva S.V., Vashakmadze N.D. et al. The concept of “ambulatory” and “non-ambulatory” in patients with Duchenne muscular dystrophy: definitions and criteria. Nervnomyshechnye bolezni = Neuromuscular Diseases 2022;12(2):10–8. (In Russ.). 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

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Copyright (c) 2023 Gremyakova T.A., Artemyeva S.B., Baybarina E.N., Vashakmadze N.D., Guzeva V.I., Gusakova E.V., Kuzenkova L.M., Lavrova A.E., Lvova O.A., Mikhaylova S.V., Nazarenko L.P., Nikitin S.S., Polyakov A.V., Dadali E.L., Rumyantsev A.G., Sakbaeva G.E., Suslov V.M., Gremyakova O.I., Stepanov A.A., Shakhovskaya N.I.

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