Advertisement

World Journal of Pediatrics

, Volume 15, Issue 3, pp 219–225 | Cite as

Progress in treatment and newborn screening for Duchenne muscular dystrophy and spinal muscular atrophy

  • Qing Ke
  • Zheng-Yan Zhao
  • Jerry R. Mendell
  • Mei Baker
  • Veronica Wiley
  • Jennifer M. Kwon
  • Lindsay N. Alfano
  • Anne M. Connolly
  • Catherine Jay
  • Hanna Polari
  • Emma Ciafaloni
  • Ming Qi
  • Robert C. Griggs
  • Michele A. GatheridgeEmail author
Review Article
  • 286 Downloads

Abstract

Background

Advances in treatment for Duchenne muscular dystrophy (DMD) and spinal muscular atrophy (SMA) hold promise for children with these disorders. Accurate genetic diagnosis, early in the disease process, will allow these treatments to be most effective. Newborn screening (NBS) for SMA has been recommended in the United States, and a pilot DMD NBS program is underway in Hangzhou, China.

Data sources

A PubMed search, limited to the past 5 years, was conducted to identify: (1) therapeutic advancements for DMD/SMA approved by the United States Food and Drug Administration or the European Medicine Agency and (2) The status of NBS for DMD/SMA.

Results

We review the current state of approved treatments for DMD/SMA. We present recommendations regarding the future of NBS for these diseases, with a focus on the outcomes and challenges of SMA NBS in New York, USA, and the DMD NBS pilot program in Hangzhou, China.

Conclusions

Approved treatments for DMD and SMA may change the natural history of these diseases. Long-term studies of these treatments are underway. To avoid the known diagnostic delay associated with these disorders and provide optimal effectiveness of these treatments, early identification of patients through NBS will be necessary. Establishing comprehensive follow-up plans for positively identified patients will need to be in place for NBS programs to be successful.

Keywords

Duchene muscular dystrophy Spinal muscular atrophy Newborn screening Neuromuscular disorders Neurology 

Notes

Author contributions

QK: acquisition of data and interpretation of data; drafting/revising the article critically for important intellectual content; final approval of the version to be published; ZZ, JRM, MB, VW, JMK, LNA, AMC, CJ, HP, EC, QM: revising the article critically for important intellectual contact; final approval of the version to be published; RCG: conceptualization, acquisition of data and interpretation of data; drafting/revising the article critically for important intellectual contact; final approval of the version to be published; MAG: acquisition of data and interpretation of data; drafting/revising the article critically for important intellectual contact; final approval of the version to be published.

Funding

There was no funding associated with this manuscript.

Compliance with ethical standards

Ethical approval

Ethical approval was not obtained since this is a literature review article.

Conflict of interest

Q. Ke, Z. Zhao, M. Baker, V. Wiley, J. M. Kwon, L. N. Alfano, C. Jay, E. Ciafaloni, M. Qi, M. A. Gatheridge: no financial benefits have been received or will be received from any party related directly or indirectly to the subject of this article; J. R. Mendell: Dr. Mendell is a Consultant for Sarepta Therapeutics, Avexis (Novartis) therapeutics, and Exonics. He receives consulting fees but no salary. He is reimbursed for presenting clinical trials that pertain to the products sponsored by these companies. He also serves on the Scientific Advisory Boards of the companies. He has no interests from or investments in products that he tests in clinical trials; A. M. Connolly: Dr. Connolly is site principal investigator for multiple studies funded by industry (Sarepta, Avexis, Biogen, PTC Therapeutics, Pfizer, BMS, Fibrogen, Italafarma and NS Pharma). In the last 2 years, Dr. Connolly has served on advisory boards for Sarepta, Avexis, Genetech-Roche, Acceleron, Astelles, Mallincrodt, and SMA Foundation. She is also on the DMSB for Catabasis. Dr. Connolly does not have stock in any company; H. Polari: employee of PerkinElmer Inc; R. C. Griggs: Dr. Griggs has received a research grant support from Marathon, PTC and Sarepta Pharmaceuticals for work related to Duchenne muscular dystrophy. He is also supported by the U.S. National Institutes of Health, the Muscular Dystrophy Association and the Parent Project for Muscular Dystrophy for research on Duchenne muscular dystrophy. He consults for Solid Bioscience.

References

  1. 1.
    Mendell JR, Shilling C, Leslie ND, Flanigan KM, al-Dahhak R, Gastier-Foster J, et al. Evidence-based path to newborn screening for Duchenne muscular dystrophy. Ann Neurol. 2012;71:304–13.CrossRefGoogle Scholar
  2. 2.
    Sugarman EA, Nagan N, Zhu H, Akmaev VR, Zhou Z, Rohlfs EM, et al. Pan-ethnic carrier screening and prenatal diagnosis for spinal muscular atrophy: clinical laboratory analysis of > 72,400 specimens. Eur J Hum Genet. 2012;20:27–32.CrossRefGoogle Scholar
  3. 3.
    Gregoretti C, Ottonello G, Chiarini Testa MB, Mastella C, Rava L, Bignamini E, et al. Survival of patients with spinal muscular atrophy type 1. Pediatrics. 2013;131:e1509–14.CrossRefGoogle Scholar
  4. 4.
    United States Food and Drug Administration. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm521263.htm (2016). Accessed 8 Jan 2019.
  5. 5.
    United States Food and Drug Administration. https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm534611.htm (2016). Accessed 8 Jan 2019.
  6. 6.
    Ottesen EW. ISS-N1 makes the First FDA-approved Drug for Spinal Muscular Atrophy. Transl Neurosci. 2017;8:1–6.CrossRefGoogle Scholar
  7. 7.
    Mendell JM. Precision genetic medicine for neuromuscular diseases. In: Proceedings of the world muscle society congress; 2018 Oct 3–6; Mendoza, Argentina.Google Scholar
  8. 8.
    Mendell JM. Molecularly-based treatments for DMD. In: Proceedings of the fourth Qianjiang inherited birth defect (SMA/DMD) forum 2018 March 16; Hangzhou, China.Google Scholar
  9. 9.
    Matthews E, Brassington R, Kuntzer T, Jichi F, Manzur AY. Corticosteroids for the treatment of Duchenne muscular dystrophy. Cochrane Database Syst Rev. 2016;2016:CD003725.Google Scholar
  10. 10.
    Griggs RC, Herr BE, Reha A, Elfring G, Atkinson L, Cwik V, et al. Corticosteroids in Duchenne muscular dystrophy: major variations in practice. Muscle Nerve. 2013;48:27–31.CrossRefGoogle Scholar
  11. 11.
    Koeks Z, Bladen CL, Salgado D, van Zwet E, Pogoryelova O, McMacken G, et al. Clinical outcomes in duchenne muscular dystrophy: a study of 5345 patients from the TREAT-NMD DMD global database. J Neuromuscul Dis. 2017;4:293–306.CrossRefGoogle Scholar
  12. 12.
    Griggs RC, Miller JP, Greenberg CR, Fehlings DL, Pestronk A, Mendell JR, et al. Efficacy and safety of deflazacort vs prednisone and placebo for Duchenne muscular dystrophy. Neurology. 2016;87:2123–31.CrossRefGoogle Scholar
  13. 13.
    Gloss D, Moxley RT 3rd, 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;86:465–72.CrossRefGoogle Scholar
  14. 14.
    Connolly AM, Florence JM, Zaidman CM, Golumbek PT, Mendell JR, Flanigan KM, et al. Clinical trial readiness in non-ambulatory boys and men with duchenne muscular dystrophy: MDA-DMD network follow-up. Muscle Nerve. 2016;54:681–9.CrossRefGoogle Scholar
  15. 15.
    Connolly AM, Malkus EC, Mendell JR, Flanigan KM, Miller JP, Schierbecker JR, et al. Outcome reliability in non-ambulatory boys/men with Duchenne muscular dystrophy. Muscle Nerve. 2015;51:522–32.CrossRefGoogle Scholar
  16. 16.
    Connolly AM, Schierbecker J, Renna R, Florence J. High dose weekly oral prednisone improves strength in boys with Duchenne muscular dystrophy. Neuromuscul Disord. 2002;12:917–25.CrossRefGoogle Scholar
  17. 17.
    Escolar DM, Hache LP, Clemens PR, Cnaan A, McDonald CM, Viswanathan V, et al. Randomized, blinded trial of weekend vs daily prednisone in Duchenne muscular dystrophy. Neurology. 2011;77:444–52.CrossRefGoogle Scholar
  18. 18.
    Guglieri M, Bushby K, McDermott MP, Hart KA, Tawil R, Martens WB, et al. Developing standardized corticosteroid treatment for Duchenne muscular dystrophy. Contemp Clin Trials. 2017;58:34–9.CrossRefGoogle Scholar
  19. 19.
    Connolly A. Care of the boy with DMD in an era of molecularly-based treatments. In: Proceedings of the fourth Qianjiang inherited birth defect (SMA/DMD) forum; 2018, Mar 15–17; Hangzhou, China; 2018.Google Scholar
  20. 20.
    Connolly AM, Zaidman CM, Golumbek PT, Cradock MM, Flanigan KM, Kuntz NL, et al. Twice weekly glucocorticosteroids in infants and young boys with duchenne muscular dystrophy. Muscle Nerve. 2019.  https://doi.org/10.1002/mus.26441.Google Scholar
  21. 21.
    Kinali M, Arechavala-Gomeza V, Feng L, Cirak S, Hunt D, Adkin C, et al. Local restoration of dystrophin expression with the morpholino oligomer AVI-4658 in Duchenne muscular dystrophy: a single-blind, placebo-controlled, dose-escalation, proof-of-concept study. Lancet Neurol. 2009;8:918–28.CrossRefGoogle Scholar
  22. 22.
    Mendell JR, Rodino-Klapac LR, Sahenk Z, Roush K, Bird L, Lowes LP, et al. Eteplirsen for the treatment of Duchenne muscular dystrophy. Ann Neurol. 2013;74:637–47.CrossRefGoogle Scholar
  23. 23.
    Mendell JR, Goemans N, Lowes LP, Alfano LN, Berry K, Shao J, et al. Longitudinal effect of eteplirsen versus historical control on ambulation in Duchenne muscular dystrophy. Ann Neurol. 2016;79:257–71.CrossRefGoogle Scholar
  24. 24.
    Dent KM, Dunn DM, von Niederhausern AC, Aoyagi AT, Kerr L, Bromberg MB, et al. Improved molecular diagnosis of dystrophinopathies in an unselected clinical cohort. Am J Med Genet A. 2005;134:295–8.CrossRefGoogle Scholar
  25. 25.
    Bushby K, Finkel R, Wong B, Barohn R, Campbell C, Comi GP, et al. Ataluren treatment of patients with nonsense mutation dystrophinopathy. Muscle Nerve. 2014;50:477–87.CrossRefGoogle Scholar
  26. 26.
    McDonald CM, Campbell C, Torricelli RE, Finkel RS, Flanigan KM, Goemans N, et al. Ataluren in patients with nonsense mutation Duchenne muscular dystrophy (ACT DMD): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017;390:1489–98.CrossRefGoogle Scholar
  27. 27.
    European Medical Agencies. Tranlarna (ataluren): an overview of Translarna and why it is authorised in the EU. https://www.ema.europa.eu/en/medicines/human/EPAR/translarna (2018). Accessed 8 Jan 2019.
  28. 28.
    Mendell JR, Campbell K, Rodino-Klapac L, Sahenk Z, Shilling C, Lewis S, et al. Dystrophin immunity in Duchenne’s muscular dystrophy. N Engl J Med. 2010;363:1429–37.CrossRefGoogle Scholar
  29. 29.
    Salva MZ, Himeda CL, Tai PW, Nishiuchi E, Gregorevic P, Allen JM, et al. Design of tissue-specific regulatory cassettes for high-level rAAV-mediated expression in skeletal and cardiac muscle. Mol Ther. 2007;15:320–9.CrossRefGoogle Scholar
  30. 30.
    Inacio P. Sarepta’s gene therapy improves muscle function in 4 boys with DMD, phase 1/2 trial shows. https://musculardystrophynews.com/2018/10/12/sarepta-dmd-gene-therapy-improves-muscle-function-4-boys-trial/ (2018). Accessed 8 Jan 2019.
  31. 31.
    Lefebvre S, Burglen L, Reboullet S, Clermont O, Burlet P, Viollet L, et al. Identification and characterization of a spinal muscular atrophy-determining gene. Cell. 1995;80:155–65.CrossRefGoogle Scholar
  32. 32.
    Parente V, Corti S. Advances in spinal muscular atrophy therapeutics. Ther Adv Neurol Disord. 2018;11:1756285618754501.CrossRefGoogle Scholar
  33. 33.
    Finkel RS, Mercuri E, Darras BT, Connolly AM, Kuntz NL, Kirschner J, et al. Nusinersen versus sham control in infantile-onset spinal muscular atrophy. N Engl J Med. 2017;377:1723–32.CrossRefGoogle Scholar
  34. 34.
    Biogen. New data presented at MDA clinical conference show benefit in motor function for infants, teens, and young adults treated with Spinraza (Nusinersen). http://investors.biogen.com/news-releases/news-release-details/new-data-presented-mda-clinical-conference-show-benefit-motor (2018). Accessed 8 Jan 2019.
  35. 35.
    Dominguez E, Marais T, Chatauret N, Benkhelifa-Ziyyat S, Duque S, Ravassard P, et al. Intravenous scAAV9 delivery of a codon-optimized SMN1 sequence rescues SMA mice. Hum Mol Genet. 2011;20:681–93.CrossRefGoogle Scholar
  36. 36.
    Valori CF, Ning K, Wyles M, Mead RJ, Grierson AJ, Shaw PJ, et al. Systemic delivery of scAAV9 expressing SMN prolongs survival in a model of spinal muscular atrophy. Sci Transl Med. 2010;2:35ra42.CrossRefGoogle Scholar
  37. 37.
    Mendell JR, Al-Zaidy S, Shell R, Arnold WD, Rodino-Klapac LR, Prior TW, et al. Single-dose gene-replacement therapy for spinal muscular atrophy. N Engl J Med. 2017;377:1713–22.CrossRefGoogle Scholar
  38. 38.
    Al-Zaidy S, Pickard AS, Kotha K, Alfano LN, Lowes L, Paul G, et al. Health outcomes in spinal muscular atrophy type 1 following AVXS-101 gene replacement therapy. Pediatr Pulmonol. 2019;54:179–85.Google Scholar
  39. 39.
    Novartis. Novartis announces FDA filing acceptance and priority review of AVXS-101, a one-time treatment designed to address the genetic root cause of SMA Type 1. https://www.novartis.com/news/media-releases/novartis-announces-fda-filing-acceptance-and-priority-review-avxs-101-one-time-treatment-designed-address-genetic-root-cause-sma-type-1(2018). Accessed 8 Jan 2019.
  40. 40.
    Gatheridge MA, Kwon JM, Mendell JM, Scheuerbrandt G, Moat SJ, Eyskens F, et al. Identifying non-duchenne muscular dystrophy-positive and false negative results in prior duchenne muscular dystrophy newborn screening programs: a review. JAMA Neurol. 2015;2015:1–7.Google Scholar
  41. 41.
    Laing N KB, Waddell L, Kreissl M, Douglas L, Wiley V. Newborn screening for duchenne muscular dystrophy in Australia. Abstract presented at: HGSA 2015. In: Proceedings of the human genetics society of Australasia annual scientific meeting, 8–11 Aug 2015, Perth, Australia.Google Scholar
  42. 42.
    Ke Q, Zhao ZY, Griggs R, Wiley V, Connolly A, Kwon J, et al. Newborn screening for Duchenne muscular dystrophy in China: follow-up diagnosis and subsequent treatment. World J Pediatr. 2017;13:197–201.CrossRefGoogle Scholar
  43. 43.
    Zhou Z. Updates in Zhejiang DMD NBS. In: Proceedings of the fourth Qianjiang inherited birth defect (SMA/DMD) forum; 16–17 Mar 2018; Hangzhou, China; 2018.Google Scholar
  44. 44.
    Birnkrant DJ, Bushby K, Bann CM, Alman BA, Apkon SD, Blackwell A, et al. Diagnosis and management of Duchenne muscular dystrophy, part 2: respiratory, cardiac, bone health, and orthopaedic management. Lancet Neurol. 2018;17:347–61.CrossRefGoogle Scholar
  45. 45.
    Birnkrant DJ, Bushby K, Bann CM, Apkon SD, Blackwell A, Brumbaugh D, et al. Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and neuromuscular, rehabilitation, endocrine, and gastrointestinal and nutritional management. Lancet Neurol. 2018;17:251–67.CrossRefGoogle Scholar
  46. 46.
    Birnkrant DJ, Bushby K, Bann CM, Apkon SD, Blackwell A, Colvin MK, et al. Diagnosis and management of Duchenne muscular dystrophy, part 3: primary care, emergency management, psychosocial care, and transitions of care across the lifespan. Lancet Neurol. 2018;17:445–55.CrossRefGoogle Scholar
  47. 47.
    Kwon JM, Abdel-Hamid HZ, Al-Zaidy SA, Mendell JR, Kennedy A, Kinnett K, et al. Clinical follow-up for duchenne muscular dystrophy newborn screening: a proposal. Muscle Nerve. 2016;54:186–91.CrossRefGoogle Scholar
  48. 48.
    Cure SMA. New York to implement newborn screening for sma October 1st. http://www.curesma.org/news/newyork-nbs-2018.html (2018). Accessed 8 Jan 2019.
  49. 49.
    Kraszewski JN, Kay DM, Stevens CF, Koval C, Haser B, Ortiz V, et al. Pilot study of population-based newborn screening for spinal muscular atrophy in New York state. Genet Med. 2018;20:608–13.CrossRefGoogle Scholar
  50. 50.
    Ciafaloni E, Fox DJ, Pandya S, Westfield CP, Puzhankara S, Romitti PA, et al. Delayed diagnosis in duchenne muscular dystrophy: data from the Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet). J Pediatr. 2009;155:380–5.CrossRefGoogle Scholar
  51. 51.
    Lin CW, Kalb SJ, Yeh WS. Delay in diagnosis of spinal muscular atrophy: a systematic literature review. Pediatr Neurol. 2015;53:293–300.CrossRefGoogle Scholar
  52. 52.
    Wang DN, Wang ZQ, Yan L, He J, Lin MT, Chen WJ, et al. Clinical and mutational characteristics of Duchenne muscular dystrophy patients based on a comprehensive database in South China. Neuromuscul Disord. 2017;27:715–22.CrossRefGoogle Scholar
  53. 53.
    Chung J, Smith AL, Hughes SC, Niizawa G, Abdel-Hamid HZ, Naylor EW, et al. Twenty-year follow-up of newborn screening for patients with muscular dystrophy. Muscle Nerve. 2016;53:570–8.CrossRefGoogle Scholar
  54. 54.
    Xu EX. Professor Shi-Wen Wu: One City, One Doctor-building up the national DMD registry network. Ann Transl Med. 2015;3:204.Google Scholar
  55. 55.
    Liu Y, Zhong L, Yuan S, van de Klundert J. Why patients prefer high-level healthcare facilities: a qualitative study using focus groups in rural and urban China. BMJ Glob Health. 2018;3:e000854.CrossRefGoogle Scholar
  56. 56.
    Campbell A, Uren M. “The invisibles”… Disability in China in the 21st century. Int J Spec Educ. 2011;26:12–24.Google Scholar

Copyright information

© Children's Hospital, Zhejiang University School of Medicine 2019

Authors and Affiliations

  • Qing Ke
    • 1
  • Zheng-Yan Zhao
    • 2
  • Jerry R. Mendell
    • 3
  • Mei Baker
    • 4
  • Veronica Wiley
    • 5
  • Jennifer M. Kwon
    • 6
  • Lindsay N. Alfano
    • 7
  • Anne M. Connolly
    • 8
  • Catherine Jay
    • 9
  • Hanna Polari
    • 10
  • Emma Ciafaloni
    • 9
  • Ming Qi
    • 11
  • Robert C. Griggs
    • 9
  • Michele A. Gatheridge
    • 12
    Email author
  1. 1.Department of Neurology, The First Affiliated Hospital, College of MedicineZhejiang UniversityHangzhouChina
  2. 2.Children’s HospitalZhejiang University School of MedicineHangzhouChina
  3. 3.Department of Pediatrics and NeurologyNationwide Children’s HospitalColumbusUSA
  4. 4.Department of PediatricsUniversity of Wisconsin School of Medicine and Public HealthMadisonUSA
  5. 5.Disciplines of Genetic Medicine and Pediatric and Child HealthUniversity of SydneySydneyAustralia
  6. 6.Department of NeurologyUniversity of Wisconsin School of Medicine and Public HealthMadisonUSA
  7. 7.Department of PediatricsNationwide Children’s HospitalColumbusUSA
  8. 8.Department of NeurologyWashington University School of MedicineSt. LouisUSA
  9. 9.Department of NeurologyUniversity of Rochester School of Medicine and DentistryRochesterUSA
  10. 10.PerkinElmer IncTurkuFinland
  11. 11.Department of Clinical LaboratoryZhejiang University School of MedicineHangzhouChina
  12. 12.Department of NeurologyUniversity of Rochester School of Medicine and DentistryRochesterUSA

Personalised recommendations