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Evolving Therapeutic Options for the Treatment of Duchenne Muscular Dystrophy

  • Current Perspectives
  • Published:
Neurotherapeutics

Abstract

Duchenne muscular dystrophy (DMD) is the most common childhood form of muscular dystrophy. It is caused by mutations in the DMD gene, leading to reduced or absent expression of the dystrophin protein. Clinically, this results in loss of ambulation, cardiomyopathy, respiratory failure, and eventually death. In the past decades, the use of corticosteroids has slowed down the disease progression. More recently, the development of genetically mediated therapies has emerged as the most promising treatment for DMD. These strategies include exon skipping with antisense oligonucleotides, gene replacement therapy with adeno-associated virus, and gene editing with CRISPR (clustered regularly interspaced short palindromic repeats) technology. In this review, we highlight the most up-to-date therapeutic progresses in the field, with emphasis on past and recent experiences, as well as the latest clinical results of DMD micro-dystrophin gene therapy. Additionally, we discuss the lessons learned along the way and the challenges encountered, all of which have helped advance the field, with the potential to finally alleviate such a devastating disease.

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References

  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(3):304–13.

  2. Mendell JR, Lloyd-Puryear M. Report of MDA muscle disease symposium on newborn screening for Duchenne muscular dystrophy. Muscle Nerve. 2013;48(1):21–6.

    Article  PubMed  Google Scholar 

  3. Manzur AY, Kuntzer T, Pike M, Swan A. Glucocorticoid corticosteroids for Duchenne muscular dystrophy. Cochrane Database Syst Rev. 2008;(1):CD003725.

  4. Mendell JR, Province MA, Moxley RT, Griggs RC, Brooke MH, Fenichel GM, et al. Clinical investigation of Duchenne muscular dystrophy. A methodology for therapeutic trials based on natural history controls. Arch Neurol. 1987;44(8):808–11.

  5. McDonald CM, Henricson EK, Abresch RT, Duong T, Joyce NC, Hu F, et al. Long-term effects of glucocorticoids on function, quality of life, and survival in patients with Duchenne muscular dystrophy: a prospective cohort study. Lancet Lond Engl. 2018;391(10119):451–61.

    Article  CAS  Google Scholar 

  6. Drachman DB, Toyka KV, Myer E. Prednisone in Duchenne muscular dystrophy. Lancet Lond Engl. 1974;2(7894):1409–12.

    Article  CAS  Google Scholar 

  7. Kissel JT, Lynn DJ, Rammohan KW, Klein JP, Griggs RC, Moxley RT, et al. Mononuclear cell analysis of muscle biopsies in prednisone- and azathioprine-treated Duchenne muscular dystrophy. Neurology. 1993;43(3 Pt 1):532–6.

    Article  CAS  PubMed  Google Scholar 

  8. Peverelli, Lorenzo et al. Histologic muscular history in steroid-treated and untreated patients with Duchenne dystrophy. Neurology. 2015; 85:1886–1893.

  9. Silversides CK, Webb GD, Harris VA, Biggar DW. Effects of deflazacort on left ventricular function in patients with Duchenne muscular dystrophy. Am J Cardiol. 2003;91(6):769–72.

    Article  CAS  PubMed  Google Scholar 

  10. Markham LW, Spicer RL, Khoury PR, Wong BL, Mathews KD, Cripe LH. Steroid therapy and cardiac function in Duchenne muscular dystrophy. Pediatr Cardiol. 2005;26(6):768–71.

    Article  CAS  PubMed  Google Scholar 

  11. Schram G, Fournier A, Leduc H, Dahdah N, Therien J, Vanasse M, 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.

    Article  PubMed  Google Scholar 

  12. Van Ruiten HJA, Marini Bettolo C, Cheetham T, Eagle M, Lochmuller H, Straub V, et al. Why are some patients with Duchenne muscular dystrophy dying young: an analysis of causes of death in North East England. Eur J Paediatr Neurol EJPN Off J Eur Paediatr Neurol Soc. 2016;20(6):904–9.

    Article  Google Scholar 

  13. Siegel IM, Miller JE, Ray RD. Failure of corticosteroid in the treatment of Duchenne (pseudo-hypertrophic) muscular dystrophy. Report of a clinically matched three year double-blind study. IMJ Ill Med J. 1974;145(1):32–33 passim.

  14. Brooke MH, Fenichel GM, Griggs RC, Mendell JR, Moxley RT, Miller JP, et al. Clinical investigation of Duchenne muscular dystrophy. Interesting results in a trial of prednisone. Arch Neurol. 1987;44(8):812–7.

  15. Mendell JR, Moxley RT, Griggs RC, Brooke MH, Fenichel GM, Miller JP, et al. Randomized, double-blind six-month trial of prednisone in Duchenne’s muscular dystrophy. N Engl J Med. 1989;320(24):1592–7.

    Article  CAS  PubMed  Google Scholar 

  16. Griggs RC, Moxley RT, Mendell JR, Fenichel GM, Brooke MH, Pestronk A, et al. Duchenne dystrophy: randomized, controlled trial of prednisone (18 months) and azathioprine (12 months). Neurology. 1993;43(3 Pt 1):520–7.

    Article  CAS  PubMed  Google Scholar 

  17. Connolly AM, Schierbecker J, Renna R, Florence J. High dose weekly oral prednisone improves strength in boys with Duchenne muscular dystrophy. Neuromuscul Disord NMD. 2002;12(10):917–25.

    Article  PubMed  Google Scholar 

  18. 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(5):444–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Mesa LE, Dubrovsky AL, Corderi J, Marco P, Flores D. Steroids in Duchenne muscular dystrophy–deflazacort trial. Neuromuscul Disord NMD. 1991;1(4):261–6.

    Article  CAS  PubMed  Google Scholar 

  20. Angelini C, Pegoraro E, Turella E, Intino MT, Pini A, Costa C. Deflazacort in Duchenne dystrophy: study of long-term effect. Muscle Nerve. 1994;17(4):386–91.

    Article  CAS  PubMed  Google Scholar 

  21. Biggar WD, Harris VA, Eliasoph L, Alman B. Long-term benefits of deflazacort treatment for boys with Duchenne muscular dystrophy in their second decade. Neuromuscul Disord NMD. 2006;16(4):249–55.

    Article  CAS  PubMed  Google Scholar 

  22. Bonifati MD, Ruzza G, Bonometto P, Berardinelli A, Gorni K, Orcesi S, et al. A multicenter, double-blind, randomized trial of deflazacort versus prednisone in Duchenne muscular dystrophy. Muscle Nerve. 2000;23(9):1344–7.

    Article  CAS  PubMed  Google Scholar 

  23. Houde S, Filiatrault M, Fournier A, Dubé J, D’Arcy S, Bérubé D, et al. Deflazacort use in Duchenne muscular dystrophy: an 8-year follow-up. Pediatr Neurol. 2008;38(3):200–6.

    Article  PubMed  Google Scholar 

  24. Bello L, Gordish-Dressman H, Morgenroth LP, Henricson EK, Duong T, Hoffman EP, et al. Prednisone/prednisolone and deflazacort regimens in the CINRG Duchenne Natural History Study. Neurology. 2015;85(12):1048–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. 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(1):27–31.

    Article  CAS  PubMed  Google Scholar 

  26. 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(20):2123–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Clark AR, Belvisi MG. Maps and legends: the quest for dissociated ligands of the glucocorticoid receptor. Pharmacol Ther. 2012;134(1):54–67.

    Article  CAS  PubMed  Google Scholar 

  28. Hoffman EP, Riddle V, Siegler MA, Dickerson D, Backonja M, Kramer WG, et al. Phase 1 trial of vamorolone, a first-in-class steroid, shows improvements in side effects via biomarkers bridged to clinical outcomes. Steroids. 2018;134:43–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Conklin LS, Damsker JM, Hoffman EP, Jusko WJ, Mavroudis PD, Schwartz BD, et al. Phase IIa trial in Duchenne muscular dystrophy shows vamorolone is a first-in-class dissociative steroidal anti-inflammatory drug. Pharmacol Res. 2018;136:140–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Hoffman EP, Schwartz BD, Mengle-Gaw LJ, Smith EC, Castro D, Mah JK, et al. Vamorolone trial in Duchenne muscular dystrophy shows dose-related improvement of muscle function. Neurology. 2019;93(13):e1312–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Smith EC, Conklin LS, Hoffman EP, Clemens PR, Mah JK, Finkel RS, et al. Efficacy and safety of vamorolone in Duchenne muscular dystrophy: an 18-month interim analysis of a non-randomized open-label extension study. PLoS Med. 2020;17(9): e1003222.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Mah JK, Clemens PR, Guglieri M, Smith EC, Finkel RS, Tulinius M, et al. Efficacy and safety of vamorolone in Duchenne muscular dystrophy: a 30-month nonrandomized controlled open-label extension trial. JAMA Netw Open. 2022;5(1): e2144178.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Guglieri M, Clemens PR, Perlman SJ, Smith EC, Horrocks I, Finkel RS, et al. Efficacy and safety of vamorolone vs placebo and prednisone among boys with Duchenne muscular dystrophy: a randomized clinical trial. JAMA Neurol. 2022;79(10):1005–14.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Klein CJ, Coovert DD, Bulman DE, Ray PN, Mendell JR, Burghes AH. Somatic reversion/suppression in Duchenne muscular dystrophy (DMD): evidence supporting a frame-restoring mechanism in rare dystrophin-positive fibers. Am J Hum Genet. 1992;50(5):950–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Lu QL, Morris GE, Wilton SD, Ly T, Artem’yeva OV, Strong P, et al. Massive idiosyncratic exon skipping corrects the nonsense mutation in dystrophic mouse muscle and produces functional revertant fibers by clonal expansion. J Cell Biol. 2000;148(5):985–96.

  36. Amanat M, Nemeth CL, Fine AS, Leung DG, Fatemi A. Antisense oligonucleotide therapy for the nervous system: from bench to bedside with emphasis on pediatric neurology. Pharmaceutics. 2022;14(11):2389.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Aartsma-Rus A, Fokkema I, Verschuuren J, Ginjaar I, van Deutekom J, van Ommen GJ, et al. Theoretic applicability of antisense-mediated exon skipping for Duchenne muscular dystrophy mutations. Hum Mutat. 2009;30(3):293–9.

    Article  PubMed  Google Scholar 

  38. Muntoni F, Torelli S, Ferlini A. Dystrophin and mutations: one gene, several proteins, multiple phenotypes. Lancet Neurol. 2003;2(12):731–40.

    Article  CAS  PubMed  Google Scholar 

  39. 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(10):918–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. 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(5):637–47.

    Article  CAS  PubMed  Google Scholar 

  41. 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(2):257–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Kinane TB, Mayer OH, Duda PW, Lowes LP, Moody SL, Mendell JR. Long-term pulmonary function in Duchenne muscular dystrophy: comparison of eteplirsen-treated patients to natural history. J Neuromuscul Dis. 2018;5(1):47–58.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Mitelman O, Abdel-Hamid HZ, Byrne BJ, Connolly AM, Heydemann P, Proud C, et al. A combined prospective and retrospective comparison of long-term functional outcomes suggests delayed loss of ambulation and pulmonary decline with long-term eteplirsen treatment. J Neuromuscul Dis. 2022;9(1):39–52.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Alfano LN, Charleston JS, Connolly AM, Cripe L, Donoghue C, Dracker R, et al. Long-term treatment with eteplirsen in nonambulatory patients with Duchenne muscular dystrophy. Medicine (Baltimore). 2019;98(26): e15858.

    Article  PubMed  Google Scholar 

  45. McDonald CM, Shieh PB, Abdel-Hamid HZ, Connolly AM, Ciafaloni E, Wagner KR, et al. Open-label evaluation of eteplirsen in patients with Duchenne muscular dystrophy amenable to exon 51 skipping: PROMOVI trial. J Neuromuscul Dis. 2021;8(6):989–1001.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Frank DE, Schnell FJ, Akana C, El-Husayni SH, Desjardins CA, Morgan J, et al. Increased dystrophin production with golodirsen in patients with Duchenne muscular dystrophy. Neurology. 2020;94(21):e2270–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Servais L, Mercuri E, Straub V, Guglieri M, Seferian AM, Scoto M, 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Scaglioni D, Catapano F, Ellis M, Torelli S, Chambers D, Feng L, et al. The administration of antisense oligonucleotide golodirsen reduces pathological regeneration in patients with Duchenne muscular dystrophy. Acta Neuropathol Commun. 2021;9(1):7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Wagner KR, Kuntz NL, Koenig E, East L, Upadhyay S, Han B, et al. Safety, tolerability, and pharmacokinetics of casimersen in patients with Duchenne muscular dystrophy amenable to exon 45 skipping: a randomized, double-blind, placebo-controlled, dose-titration trial. Muscle Nerve. 2021;64(3):285–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Clemens PR, Rao VK, Connolly AM, Harper AD, Mah JK, Smith EC, 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.

    Article  PubMed  Google Scholar 

  51. Clemens PR, Rao VK, Connolly AM, Harper AD, Mah JK, McDonald CM, et al. Efficacy and safety of viltolarsen in boys with Duchenne muscular dystrophy: results from the phase 2, open-label, 4-year extension study. J Neuromuscul Dis. 2023;

  52. Oechsel KF, Cartwright MS. Combination therapy with onasemnogene and risdiplam in spinal muscular atrophy type 1. Muscle Nerve. 2021;64(4):487–90.

    Article  PubMed  Google Scholar 

  53. Wu B, Lu P, Cloer C, Shaban M, Grewal S, Milazi S, et al. Long-term rescue of dystrophin expression and improvement in muscle pathology and function in dystrophic mdx mice by peptide-conjugated morpholino. Am J Pathol. 2012;181(2):392–400.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Welch EM, Barton ER, Zhuo J, Tomizawa Y, Friesen WJ, Trifillis P, et al. PTC124 targets genetic disorders caused by nonsense mutations. Nature. 2007;447(7140):87–91.

    Article  CAS  PubMed  Google Scholar 

  55. Finkel RS, Flanigan KM, Wong B, Bönnemann C, Sampson J, Sweeney HL, et al. Phase 2a study of ataluren-mediated dystrophin production in patients with nonsense mutation Duchenne muscular dystrophy. PLoS ONE. 2013;8(12): e81302.

    Article  PubMed  PubMed Central  Google Scholar 

  56. 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 Lond Engl. 2017;390(10101):1489–98.

    Article  CAS  Google Scholar 

  57. Mercuri E, Osorio AN, Muntoni F, Buccella F, Desguerre I, Kirschner J, et al. Safety and effectiveness of ataluren in patients with nonsense mutation DMD in the STRIDE Registry compared with the CINRG Duchenne Natural History Study (2015–2022): 2022 interim analysis. J Neurol. 2020;270(8):3896–913.

    Article  Google Scholar 

  58. Long-term outcomes of ataluren in Duchenne muscular dystrophy. Available at: https://clinicaltrials.gov/ct2/show/NCT03179631. Accessed August 23, 2020.

  59. England SB, Nicholson LV, Johnson MA, Forrest SM, Love DR, Zubrzycka-Gaarn EE, et al. Very mild muscular dystrophy associated with the deletion of 46% of dystrophin. Nature. 1990;343(6254):180–2.

    Article  CAS  PubMed  Google Scholar 

  60. Marshall E. Gene therapy death prompts review of adenovirus vector. Science. 1999;286(5448):2244–5.

    Article  CAS  PubMed  Google Scholar 

  61. Atchison RW, Casto BC, Hammon WM. Adenovirus-associated defective virus particles. Science. 1965;149(3685):754–6.

    Article  CAS  PubMed  Google Scholar 

  62. Hoggan MD, Blacklow NR, Rowe WP. Studies of small DNA viruses found in various adenovirus preparations: physical, biological, and immunological characteristics. Proc Natl Acad Sci U S A. 1966;55(6):1467–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Naso MF, Tomkowicz B, Perry WL, Strohl WR. Adeno-associated virus (AAV) as a vector for gene therapy. BioDrugs Clin Immunother Biopharm Gene Ther. 2017;31(4):317–34.

    CAS  Google Scholar 

  64. McCarty DM, Monahan PE, Samulski RJ. Self-complementary recombinant adeno-associated virus (scAAV) vectors promote efficient transduction independently of DNA synthesis. Gene Ther. 2001;8(16):1248–54.

    Article  CAS  PubMed  Google Scholar 

  65. Wang B, Li J, Xiao X. Adeno-associated virus vector carrying human minidystrophin genes effectively ameliorates muscular dystrophy in mdx mouse model. Proc Natl Acad Sci U S A. 2000;97(25):13714–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Harper SQ, Hauser MA, DelloRusso C, Duan D, Crawford RW, Phelps SF, et al. Modular flexibility of dystrophin: implications for gene therapy of Duchenne muscular dystrophy. Nat Med. 2008;8(3):253–61.

    Article  Google Scholar 

  67. Mendell JR, Sahenk Z, Lehman K, Nease C, Lowes LP, Miller NF, et al. Assessment of systemic delivery of rAAVrh74.MHCK7.micro-dystrophin in children with Duchenne muscular dystrophy: a nonrandomized controlled trial. JAMA Neurol. 2020;77(9):1122–31.

  68. Bönnemann CG, Belluscio BA, Braun S, et al. A collaborative analysis by clinical trial sponsors and academic experts of anti-transgene SAEs in studies of gene therapy for DMD. Presented at: ASGCT 25th Annual Meeting, May 16–19, 2022; Washington DC.

  69. 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(15):1429–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Chen G, Wei T, Yang H, Li G, Li H. CRISPR-based therapeutic gene editing for Duchenne muscular dystrophy: advances, challenges and perspectives. Cells. 2022;11(19):2964.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Bengtsson NE, Hall JK, Odom GL, Phelps MP, Andrus CR, Hawkins RD, et al. Muscle-specific CRISPR/Cas9 dystrophin gene editing ameliorates pathophysiology in a mouse model for Duchenne muscular dystrophy. Nat Commun. 2017;8:14454.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Long C, Amoasii L, Mireault AA, McAnally JR, Li H, Sanchez-Ortiz E, et al. Postnatal genome editing partially restores dystrophin expression in a mouse model of muscular dystrophy. Science. 2016;351(6271):400–3.

    Article  CAS  PubMed  Google Scholar 

  73. Amoasii L, Hildyard JCW, Li H, Sanchez-Ortiz E, Mireault A, Caballero D, et al. Gene editing restores dystrophin expression in a canine model of Duchenne muscular dystrophy. Science. 2018;362(6410):86–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Angela Lek, Brenda Wong, Allison Keeler, Meghan Blackwood, Kaiyue Ma, Shushu Huang, et al. Unexpected death of a Duchenne muscular dystrophy patient in an N-of-1 trial of rAAV9-delivered CRISPR-transactivator. medRxiv. 2023;2023.05.16.23289881

  75. Min YL, Chemello F, Li H, Rodriguez-Caycedo C, Sanchez-Ortiz E, Mireault AA, et al. Correction of three prominent mutations in mouse and human models of Duchenne muscular dystrophy by single-cut genome editing. Mol Ther J Am Soc Gene Ther. 2020;28(9):2044–55.

    Article  CAS  Google Scholar 

  76. Moretti A, Fonteyne L, Giesert F, Hoppmann P, Meier AB, Bozoglu T, et al. Somatic gene editing ameliorates skeletal and cardiac muscle failure in pig and human models of Duchenne muscular dystrophy. Nat Med. 2020;26(2):207–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. 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(18):1713–22.

    Article  CAS  PubMed  Google Scholar 

  78. Hakim CH, Wasala NB, Nelson CE, Wasala LP, Yue Y, Louderman JA, et al. AAV CRISPR editing rescues cardiac and muscle function for 18 months in dystrophic mice. JCI Insight. 2018;3(23):e124297, 124297.

  79. Min YL, Li H, Rodriguez-Caycedo C, Mireault AA, Huang J, Shelton JM, et al. CRISPR-Cas9 corrects Duchenne muscular dystrophy exon 44 deletion mutations in mice and human cells. Sci Adv. 2019;5(3):eaav4324.

  80. Ren C, Kumar S, Shaw DR, Ponnazhagan S. Genomic stability of self-complementary adeno-associated virus 2 during early stages of transduction in mouse muscle in vivo. Hum Gene Ther. 2005;16(9):1047–57.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The micro-dystrophin gene therapy clinical trials have been done with Sarepta Therapeutics as the Industry Sponsor.

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  1. Center for Gene Therapy, Department of Pediatrics, Abigail Wexner Research Institute, Nationwide Children’s Hospital, Ohio State University, Columbus, OH, 43205, USA

    Eleonora S. D’Ambrosio & Jerry R. Mendell

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D’Ambrosio, E.S., Mendell, J.R. Evolving Therapeutic Options for the Treatment of Duchenne Muscular Dystrophy. Neurotherapeutics 20, 1669–1681 (2023). https://doi.org/10.1007/s13311-023-01423-y

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