[en] Duchenne muscular dystrophy is an X-linked disease caused by the absence of functional dystrophin in the muscle cells. Major advances have led to the development of gene therapies, tools that induce exon skipping, and other therapeutic approaches, including treatments targeting molecular pathways downstream of the absence of functional dystrophin. However, glucocorticoids remain the only treatment unequivocally shown to slow disease progression, despite the adverse effects associated with their long-term use. Besides glucocorticoids, which are standard care, five compounds have received regulatory approval in some but not all jurisdictions, with further efficacy results being awaited. Several compounds with promising results in early-phase clinical trials have not met their efficacy endpoints in late-phase trials, but the clinical development of many other compounds is ongoing. The current landscape is complicated by the number of compounds in various stages of development, their various mechanisms of action, and their genotype-specific applicability. The difficulties of clinical development that arise from both the rarity and variability of Duchenne muscular dystrophy might be overcome in the future by use of sensitive biomarkers, natural history data, and ameliorated trial designs.
Disciplines :
Neurology Pediatrics
Author, co-author :
Markati, Theodora; MDUK Oxford Neuromuscular Centre, Department of Paediatrics, University of Oxford, Oxford, United Kingdom
Oskoui, Maryam; Department of Pediatrics and Department of Neurology Neurosurgery, McGill University, Montreal, Canada ; Centre for Outcomes Research and Evaluation, Research Institute of the McGill University Health Centre, Montreal, Canada
Farrar, Michelle A; Discipline of Paediatrics, School of Clinical Medicine, UNSW Medicine and Health, UNSW Sydney, Sydney, Australia ; Department of Neurology, Sydney Children's Hospital, Randwick, Australia
Duong, Tina; Department of Neurology and Neurological Sciences, Stanford University, Stanford, United States
Goemans, Nathalie; Department of Pediatric Neurology, University Hospitals Leuven, Leuven, Belgium
Servais, Laurent ; Centre Hospitalier Universitaire de Liège - CHU > > Service de pédiatrie ; MDUK Oxford Neuromuscular Centre, Department of Paediatrics, University of Oxford, Oxford, United Kingdom
Language :
English
Title :
Emerging therapies for Duchenne muscular dystrophy
We thank Andrea Quaiattini, assistant librarian at the Schulich Library of Physical Sciences, Life Sciences, and Engineering, McGill University, for assistance in creating and running the literature search strategy.TM is an Onassis Foundation Scholar (Scholarship ID: F ZQ 040-1/2020-2021). MO serves as a methodologist for the American Academy of Neurology and a volunteer member of the Medical and Scientific Advisory Board for Muscular Dystrophy Canada; and is a clinical research scholar supported by the Fonds de recherche du Québec Santé. MAF received grant support from the National Health and Medical Research Council of Australia (APP1194940). NG has participated on data safety monitoring or advisory boards of Pfizer, Wave Life Sciences, Sarepta Therapeutics, Pliant Therapeutics, and Santhera Pharmaceuticals. LS has participated on data safety monitoring or advisory boards of FibroGen, Santhera Pharmaceuticals, RegenexBio, and Catabasis Pharmaceuticals, and is supported by a grant from Muscular Dystrophy UK. TD has received payment for lectures from Sarepta Therapeutics. NG has received payment for lectures from Sarepta Therapeutics and Santhera Pharmaceuticals. TD has received consulting fees from Pfizer, Edgewise Therapeutics, Dyne Therapeutics, Solid Biosciences, and ATOM International. MAF has received consulting fees from Pfizer. LS has received consulting fees from Sarepta, Pfizer, and F Hoffmann La Roche. TD is a member of TreatNMD Advisory Committee for Therapeutics (TACT), Treat-NMD Duchenne muscular dystrophy database committee, CureDuchenne, and Parent Project Muscular Dystrophy. LS is executive secretary of the World Muscle Society.
Mah, JK, Korngut, L, Dykeman, J, A systematic review and meta-analysis on the epidemiology of Duchenne and Becker muscular dystrophy. Neuromuscul Disord 6 (2014), 482–491.
Thangarajh, M, Hendriksen, J, McDermott, MP, et al. Relationships between DMD mutations and neurodevelopment in dystrophinopathy. Neurology 93 (2019), e1597–e1604.
Birnkrant, DJ, Bushby, K, Bann, CM, et al. Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and neuromuscular, rehabilitation, endocrine, and gastrointestinal and nutritional management. Lancet Neurol 17 (2018), 251–267.
Birnkrant, DJ, Bushby, K, Bann, CM, et al. Diagnosis and management of Duchenne muscular dystrophy, part 2: respiratory, cardiac, bone health, and orthopaedic management. Lancet Neurol 17 (2018), 347–361.
Birnkrant, DJ, Bushby, K, Bann, CM, 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 17 (2018), 445–455.
Mendell, JR, Sahenk, Z, Lehman, K, et al. Assessment of systemic delivery of rAAVrh74.MHCK7.micro-dystrophin in children with Duchenne muscular dystrophy: a nonrandomized controlled trial. JAMA Neurol 77 (2020), 1122–1131.
Bushby, K, Finkel, R, Wong, B, et al. Ataluren treatment of patients with nonsense mutation dystrophinopathy. Muscle Nerve 50 (2014), 477–487.
McDonald, CM, Campbell, C, Torricelli, RE, et al. Ataluren in patients with nonsense mutation Duchenne muscular dystrophy (ACT DMD): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet 390 (2017), 1489–1498.
Campbell, C, Barohn, RJ, Bertini, E, et al. Meta-analyses of ataluren randomized controlled trials in nonsense mutation Duchenne muscular dystrophy. J Comp Eff Res 9 (2020), 973–984.
Kong, R, O'Mara, E, Luo, X, Trifillis, P, Werner, C, McIntosh, J, A phase 2 trial of the safety and pharmacokinetics of ataluren in patients aged >=2 to <5 years with nonsense mutation Duchenne muscular dystrophy. Neuromuscul Disord 28:suppl 1 (2018), S12–S13.
Muntoni, F, Desguerre, I, Guglieri, M, et al. Ataluren use in patients with nonsense mutation Duchenne muscular dystrophy: patient demographics and characteristics from the STRIDE Registry. J Comp Eff Res 8 (2019), 1187–1200.
Mercuri, E, Muntoni, F, Osorio, AN, et al. Safety and effectiveness of ataluren: comparison of results from the STRIDE Registry and CINRG DMD Natural History Study. J Comp Eff Res 9 (2020), 341–360.
Charleston, JS, Schnell, FJ, Dworzak, J, et al. Eteplirsen treatment for Duchenne muscular dystrophy: exon skipping and dystrophin production. Neurology 90 (2018), e2146–e2154.
Mendell, JR, Goemans, N, Lowes, LP, et al. Longitudinal effect of eteplirsen versus historical control on ambulation in Duchenne muscular dystrophy. Ann Neurol 79 (2016), 257–271.
Mendell, JR, Khan, N, Sha, N, et al. Comparison of long-term ambulatory function in patients with Duchenne muscular dystrophy treated with eteplirsen and matched natural history controls. J Neuromuscul Dis 8 (2021), 469–479.
McDonald, CM, Shieh, PB, Abdel-Hamid, HZ, et al. Open-label evaluation of eteplirsen in patients with Duchenne muscular dystrophy amenable to exon 51 skipping: PROMOVI trial. J Neuromuscul Dis 8 (2021), 989–1001.
Wagner, KR, Kuntz, NL, Koenig, E, 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 64 (2021), 285–292.
Frank, DE, Schnell, FJ, Akana, C, et al. Increased dystrophin production with golodirsen in patients with Duchenne muscular dystrophy. Neurology 94 (2020), e2270–e2282.
Scaglioni, D, Catapano, F, Ellis, M, et al. The administration of antisense oligonucleotide golodirsen reduces pathological regeneration in patients with Duchenne muscular dystrophy. Acta Neuropathol Commun, 9, 2021, 7.
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 32 (2022), 29–39.
Clemens, PR, Rao, VK, Connolly, AM, 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 77 (2020), 982–991.
Komaki, H, Takeshima, Y, Matsumura, T, et al. Viltolarsen in Japanese Duchenne muscular dystrophy patients: a phase 1/2 study. Ann Clin Transl Neurol 7 (2020), 2393–2408.
Taylor, M, Jefferies, J, Byrne, B, et al. Cardiac and skeletal muscle effects in the randomized HOPE-Duchenne trial. Neurology 92 (2019), e866–e878.
Wang, D, Tai, PWL, Gao, G, Adeno-associated virus vector as a platform for gene therapy delivery. Nat Rev Drug Discov 18 (2019), 358–378.
Kuzmin, DA, Shutova, MV, Johnston, NR, et al. The clinical landscape for AAV gene therapies. Nat Rev Drug Discov 20 (2021), 173–174.
Davies, KE, Guiraud, S, Micro-dystrophin genes bring hope of an effective therapy for Duchenne muscular dystrophy. Mol Ther 27 (2019), 486–488.
Mendell, JR, Campbell, K, Rodino-Klapac, L, et al. Dystrophin immunity in Duchenne's muscular dystrophy. N Engl J Med 363 (2010), 1429–1437.
The Pfizer DMD gene therapy team. Pfizer's statement to the community. https://www.parentprojectmd.org/wp-content/uploads/2021/12/DMD-Study-1001-Update_Letter-to-the-Community.pdf, December, 2021. (Accessed 12 January 2022)
Belluscio B, Beaverson K, Garnier N, et al. Safety and efficacy of PF-06939926 gene therapy in boys with Duchenne muscular dystrophy: update on data from the phase 1B study. Muscular Dystrophy Association (MDA) Conference; March 15–18, 2021 (poster 77).
Wexler, M, Phase 3 trial of Pfizer's gene therapy expected to open in US in June. https://musculardystrophynews.com/2022/05/03/phase-3-trial-of-pfizers-gene-therapy-expected-to-open-in-us-in-june/, May 3, 2022. (Accessed 9 May 2022)
Wexler, M, FDA puts 2nd clinical hold on IGNITE DMD trial of gene therapy SGT-001 due to patient reaction. https://musculardystrophynews.com/2019/11/13/ignite-dmd-gene-therapy-sgt-001-trial-2nd-fda-clinical-hold/, Nov 13, 2019. (Accessed 12 January 2022)
Muntoni, F, Domingos, J, Manzur, AY, et al. Categorising trajectories and individual item changes of the North Star Ambulatory Assessment in patients with Duchenne muscular dystrophy. PLoS ONE Electron Resour, 14, 2019, e0221097.
Mendell JR, Shieh PB, Sahenk Z. 1A Phase 2 clinical trial evaluating the safety and efficacy of SRP-9001 for treating patients with Duchenne muscular dystrophy. World Muscle Society Congress; Sept 20–24, 2021 (abstr EP.254a).
Bladen, CL, Salgado, D, Monges, S, et al. The TREAT-NMD DMD global database: analysis of more than 7,000 Duchenne muscular dystrophy mutations. Hum Mutat 36 (2015), 395–402.
Bello, L, Morgenroth, LP, Gordish-Dressman, H, et al. DMD genotypes and loss of ambulation in the CINRG Duchenne Natural History Study. Neurology 87 (2016), 401–409.
Aartsma-Rus, A, Ginjaar, IB, Bushby, K, The importance of genetic diagnosis for Duchenne muscular dystrophy. J Med Genet 53 (2016), 145–151.
Welch, EM, Barton, ER, Zhuo, J, et al. PTC124 targets genetic disorders caused by nonsense mutations. Nature 447 (2007), 87–91.
Rinaldi, C., Wood, M., Antisense oligonucleotides: the next frontier for treatment of neurological disorders. Nat Rev Neurol 14 (2018), 9–21.
Niks, EH, Aartsma-Rus, A, Exon skipping: a first in class strategy for Duchenne muscular dystrophy. Expert Opin Biol Ther 17 (2017), 225–236.
Hammond, SM, Aartsma-Rus, A, Alves, S, et al. Delivery of oligonucleotide-based therapeutics: challenges and opportunities. EMBO Mol Med, 13, 2021, e13243.
Roberts, TC, Langer, R, Wood, MJA, Advances in oligonucleotide drug delivery. Nat Rev Drug Discov 19 (2020), 673–694.
Aartsma-Rus, A, Arechavala-Gomeza, V, Why dystrophin quantification is key in the eteplirsen saga. Nat Rev Neurol 14 (2018), 454–456.
Sarepta Therapeutics. Sarepta Therapeutics reports positive clinical results from phase 2 MOMENTUM study of SRP-5051 in patients with Duchenne muscular dystrophy amenable to skipping exon 51. https://investorrelations.sarepta.com/news-releases/news-release-details/sarepta-therapeutics-reports-positive-clinical-results-phase-2, March 5, 2021. (Accessed 12 January 2022)
Goemans, N, Mercuri, E, Belousova, E, et al. A randomized placebo-controlled phase 3 trial of an antisense oligonucleotide, drisapersen, in Duchenne muscular dystrophy. Neuromuscul Disord 28 (2018), 4–15.
Goemans, NM, Tulinius, M, van den Hauwe, M, et al. Long-term efficacy, safety, and pharmacokinetics of drisapersen in Duchenne muscular dystrophy: results from an open-label extension study. PLoS ONE Electron Resour, 11, 2016, e0161955.
McDonald, CM, Wong, B, Flanigan, KM, et al. Placebo-controlled phase 2 trial of drisapersen for Duchenne muscular dystrophy. Ann Clin Transl Neurol 5 (2018), 913–926.
Wexler, M, Wave Life Sciences discontinues development of suvodirsen for DMD. https://musculardystrophynews.com/2019/12/17/wave-life-sciences-discontinues-suvodirsen-development-for-dmd/, Dec 17, 2019. (Accessed 12 January 2022)
Brogna, C, Coratti, G, Pane, M, et al. Long-term natural history data in Duchenne muscular dystrophy ambulant patients with mutations amenable to skip exons 44, 45, 51 and 53. PLoS One, 14, 2019, e0218683.
Sampaolesi, M, Blot, S, D'Antona, G, et al. Mesoangioblast stem cells ameliorate muscle function in dystrophic dogs. Nature 444 (2006), 574–579.
Cossu, G, Previtali, SC, Napolitano, S, et al. Intra-arterial transplantation of HLA-matched donor mesoangioblasts in Duchenne muscular dystrophy. EMBO Mol Med 7 (2015), 1513–1528.
McDonald, CM, Marbán, E, Hendrix, S, et al. Repeated intravenous cardiosphere-derived cell therapy in late-stage Duchenne muscular dystrophy (HOPE-2): a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Lancet 399 (2022), 1049–1058.
Barthélémy, F, Wein, N, Personalized gene and cell therapy for Duchenne muscular dystrophy. Neuromuscul Disord 28 (2018), 803–824.
Young, CS, Hicks, MR, Ermolova, NV, et al. A single CRISPR-Cas9 deletion strategy that targets the majority of dmd patients restores dystrophin function in hiPSC-derived muscle cells. Cell Stem Cell 18 (2016), 533–540.
Guiraud, S, Roblin, D, Kay Davies, E, The potential of utrophin modulators for the treatment of Duchenne muscular dystrophy. Expert Opin Orphan Drugs 6 (2018), 179–192.
Tinsley, J, Deconinck, N, Fisher, R, et al. Expression of full-length utrophin prevents muscular dystrophy in mdx mice. Nat Med 4 (1998), 1441–1444.
Gilbert, R, Nalbantoglu, J, Petrof, BJ, et al. Adenovirus-mediated utrophin gene transfer mitigates the dystrophic phenotype of mdx mouse muscles. Hum Gene Ther 10 (1999), 1299–1310.
Muntoni, F, Tejura, B, Spinty, S, et al. A phase 1b trial to assess the pharmacokinetics of ezutromid in pediatric Duchenne muscular dystrophy patients on a balanced diet. Clin Pharmacol Drug Dev 8 (2019), 922–933.
Muntoni, F, Layton, G, Bhattacharya, I, et al. Ezutromid significantly reduced muscle damage whilst maintaining utrophin in patients with Duchenne muscular dystrophy after 24 weeks of treatment. Neurology 90 (2018), e2185–e2186.
Soblechero-Martín, P, López-Martínez, A, Puente-Ovejero, L, Vallejo-Illarramendi, A, Arechavala-Gomeza, V, Utrophin modulator drugs as potential therapies for Duchenne and Becker muscular dystrophies. Neuropathol Appl Neurobiol 47 (2021), 711–723.
Wilkinson, IVL, Perkins, KJ, Dugdale, H, et al. Chemical proteomics and phenotypic profiling identifies the aryl hydrocarbon receptor as a molecular target of the utrophin modulator ezutromid. Angew Chem Int Ed Engl 59 (2019), 2420–2428.
Chicoine, LG, Rodino-Klapac, LR, Shao, G, et al. Vascular delivery of rAAVrh74.MCK.GALGT2 to the gastrocnemius muscle of the rhesus macaque stimulates the expression of dystrophin and laminin α2 surrogates. Mol Ther 22 (2014), 713–724.
McDonald, CM, 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 61 (2020), 26–35.
Mavroudis, PD, van den Anker, J, Conklin, LS, et al. Population pharmacokinetics of vamorolone (VBP15) in healthy men and boys with Duchenne muscular dystrophy. J Clin Pharmacol 59 (2019), 979–988.
Li, X, Conklin, LS, van den Anker, J, Hoffman, EP, Clemens, PR, Jusko, WJ, Exposure-response analysis of vamorolone (VBP15) in boys with Duchenne muscular dystrophy. J Clin Pharmacol 60 (2020), 1385–1396.
Conklin, LS, Damsker, JM, Hoffman, EP, et al. Phase IIa trial in Duchenne muscular dystrophy shows vamorolone is a first-in-class dissociative steroidal anti-inflammatory drug. Pharmacol Res 136 (2018), 140–150.
Hoffman, EP, Schwartz, BD, Mengle-Gaw, LJ, et al. Vamorolone trial in Duchenne muscular dystrophy shows dose-related improvement of muscle function. Neurology 93 (2019), e1312–e1323.
Smith, EC, Conklin, LS, Hoffman, EP, 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 Public Libr Sci, 17, 2020, e1003222.
Vita, GL, Sframeli, M, Licata, N, et al. A phase 1/2 study of flavocoxid, an oral NF-kappaB inhibitor, in Duchenne muscular dystrophy. Brain Sci, 11, 2021, 115.
Hafner, P, Bonati, U, Klein, A, et al. Effect of combination l-citrulline and metformin treatment on motor function in patients with Duchenne muscular dystrophy: a randomized clinical trial. JAMA Netw Open, 2, 2019, e1914171.
Hafner, P, Bonati, U, Erne, B, et al. Improved muscle function in Duchenne muscular dystrophy through l-arginine and metformin: an investigator-initiated, open-label, single-center, proof-of-concept-study. PLoS ONE Electron Resour, 11, 2016, e0147634.
Salehi, F, Zeinaloo, A, Riasi, HR, Shamloo, AS, Effectiveness of coenzyme Q10 on echocardiographic parameters of patients with Duchenne muscular dystrophy. Electron Physician Electron Resour 9 (2017), 3896–3904.
Previtali, SC, Gidaro, T, Díaz-Manera, J, et al. Rimeporide as a first-in-class NHE-1 inhibitor: results of a phase Ib trial in young patients with Duchenne muscular dystrophy. Pharmacol Res, 159, 2020, 104999.
Bettica, P, Petrini, S, D'Oria, V, et al. Histological effects of givinostat in boys with Duchenne muscular dystrophy. Neuromuscul Disord 26 (2016), 643–649.
Tsabari, R, Simchovitz, E, Lavi, E, et al. Safety and clinical outcome of tamoxifen in Duchenne muscular dystrophy. Neuromuscul Disord 31 (2021), 803–813.
Sienkiewicz, D, Kulak, W, Okurowska-Zawada, B, et al. Efficacy and the safety of granulocyte colony-stimulating factor treatment in patients with muscular dystrophy: a non-randomized clinical trial. Front Neurol, 8, 2017, 566.
Sienkiewicz, D, Kulak, W, Paszko-Patej, G, Okurowska-Zawada, B, Sienkiewicz, J, Kulak, P, Biochemical changes in blood of patients with duchenne muscular dystrophy treated with granulocyte-colony stimulating factor. BioMed Res Int, 2019, 2019, 4789101.
McDonald, CM, Henricson, EK, Abresch, RT, 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 391 (2018), 451–461.
McDonald, CM, 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 61 (2020), 26–35.
Connolly, AM, Zaidman, CM, Golumbek, PT, et al. Twice-weekly glucocorticosteroids in infants and young boys with Duchenne muscular dystrophy. Muscle Nerve 59 (2019), 650–657.
Ricotti, V, Ridout, DA, 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 84 (2013), 698–705.
Santhera Pharmaceuticals Holding. Santhera and ReveraGen announce positive and statistically highly significant topline results with vamorolone in pivotal VISION-DMD study. https://www.globenewswire.com/news-release/2021/06/01/2239124/0/en/Santhera-and-ReveraGenAnnounce-Positive-and-Statistically-Highly-Significant-Topline-Results-with-Vamorolone-in-Pivotal-VISION-DMD-Study.html, June 1, 2021. (Accessed 12 January 2022)
Finkel, RS, McDonald, CM, Sweeney, HL, et al. A randomized, double-blind, placebo-controlled, global phase 3 study of edasalonexent in pediatric patients with Duchenne muscular dystrophy: results of the PolarisDMD trial. Neuromuscul Dis 8 (2021), 769–784.
Nio, Y, Tanaka, M, Hirozane, Y, et al. Phosphodiesterase 4 inhibitor and phosphodiesterase 5 inhibitor combination therapy has antifibrotic and anti-inflammatory effects in mdx mice with Duchenne muscular dystrophy. FASEB J Off Publ Fed Am Soc Exp Biol 31 (2017), 5307–5320.
Percival, JM, Whitehead, NP, Adams, ME, Adamo, CM, Beavo, JA, Froehner, SC, Sildenafil reduces respiratory muscle weakness and fibrosis in the mdx mouse model of Duchenne muscular dystrophy. J Pathol 228 (2012), 77–87.
Victor, RG, Sweeney, HL, Finkel, R, et al. A phase 3 randomized placebo-controlled trial of tadalafil for Duchenne muscular dystrophy. Neurology 89 (2017), 1811–1820.
Leung, DG, Herzka, DA, Thompson, WR, et al. Sildenafil does not improve cardiomyopathy in Duchenne/Becker muscular dystrophy. Ann Neurol 76 (2014), 541–549.
Allen, DG, Whitehead, NP, Froehner, SC, Absence of dystrophin disrupts skeletal muscle signaling: roles of Ca2+, reactive oxygen species, and nitric oxide in the development of muscular dystrophy. Physiol Rev 96 (2016), 253–305.
Servais, L, Straathof, CSM, Schara, U, et al. Long-term data with idebenone on respiratory function outcomes in patients with Duchenne muscular dystrophy. Neuromuscul Disord 30 (2020), 5–16.
McDonald, CM, Meier, T, Voit, T, et al. Idebenone reduces respiratory complications in patients with Duchenne muscular dystrophy. Neuromuscul Disord 26 (2016), 473–480.
Buyse, GM, Voit, T, Schara, U, et al. Efficacy of idebenone on respiratory function in patients with Duchenne muscular dystrophy not using glucocorticoids (DELOS): a double-blind randomised placebo-controlled phase 3 trial. Lancet 385 (2015), 1748–1757.
Chahine, M, Bkaily, G, Nader, M, et al. NHE-1-dependent intracellular sodium overload in hypertrophic hereditary cardiomyopathy: prevention by NHE-1 inhibitor. J Mol Cell Cardiol 38 (2005), 571–582.
Bell, EL, Shine, RW, Dwyer, P, et al. PPARδ modulation rescues mitochondrial fatty acid oxidation defects in the mdx model of muscular dystrophy. Mitochondrion 46 (2019), 51–58.
Wagner, KR, Liu, X, Chang, X, Allen, RE, Muscle regeneration in the prolonged absence of myostatin. Proc Natl Acad Sci USA 102 (2005), 2519–2524.
Wagner, KR, Wong, BL, Byrne, BJ, et al. A randomised, placebo-controlled, double-blind, phase 1B/2 study of the novel anti-myostatin adnectin BMS-986089/RG6206 in ambulatory boys with Duchenne muscular dystrophy. Dev Med Child Neurol, 59(suppl 4), 2017, 33.
Wagner, KR, Abdel-Hamid, HZ, Mah, JK, et al. Randomized phase 2 trial and open-label extension of domagrozumab in Duchenne muscular dystrophy. Neuromuscul Disord 30 (2020), 492–502.
Campbell, C, McMillan, HJ, Mah, JK, et al. Myostatin inhibitor ACE-031 treatment of ambulatory boys with Duchenne muscular dystrophy: results of a randomized, placebo-controlled clinical trial. Muscle Nerve 55 (2017), 458–464.
Wagner, KR, The elusive promise of myostatin inhibition for muscular dystrophy. Curr Opin Neurol 33 (2020), 621–628.
Rybalka, E, Timpani, CA, Debruin, DA, Bagaric, RM, Campelj, DG, Hayes, A, The failed clinical story of myostatin inhibitors against Duchenne muscular dystrophy: exploring the biology behind the battle. Cells, 9, 2020, 2657.
Consalvi, S, Mozzetta, C, Bettica, P, et al. Preclinical Studies in the mdx mouse model of Duchenne muscular dystrophy with the histone deacetylase inhibitor givinostat. Mol Med 19 (2013), 79–87.
Italfarmaco Group. Italfarmaco Group announces positive topline data from phase 3 trial showing beneficial effect of givinostat in patients with Duchenne muscular dystrophy. https://www.businesswire.com/news/home/20220625005001/en/Italfarmaco-Group-Announces-Positive-Topline-Data-from-Phase-3-Trial-Showing-Beneficial-Effect-of-Givinostat-in-Patients-with-Duchenne-Muscular-Dystrophy, June 25, 2022. (Accessed 26 June 2022)
Kota, J, Handy, CR, Haidet, AM, et al. Follistatin gene delivery enhances muscle growth and strength in nonhuman primates. Sci Transl Med, 1, 2009, 6ra15.
Zhu, J, Li, Y, Lu, A, et al. Follistatin improves skeletal muscle healing after injury and disease through an interaction with muscle regeneration, angiogenesis, and fibrosis. Am J Pathol 179 (2011), 915–930.
Mendell, JR, Sahenk, Z, Malik, V, et al. A phase 1/2a follistatin gene therapy trial for Becker muscular dystrophy. Mol Ther 23 (2015), 192–201.
Sun, G, Haginoya, K, Wu, Y, et al. Connective tissue growth factor is overexpressed in muscles of human muscular dystrophy. J Neurol Sci 267 (2008), 48–56.
Dorchies, OM, Reutenauer-Patte, J, Dahmane, E, et al. The anticancer drug tamoxifen counteracts the pathology in a mouse model of Duchenne muscular dystrophy. Am J Pathol 182 (2013), 485–504.
Le Guiner, C, Servais, L, Montus, M, et al. Long-term microdystrophin gene therapy is effective in a canine model of Duchenne muscular dystrophy. Nat Commun, 8, 2017, 16105.
Pagliarulo, N, Fourth trial volunteer dies in Astellas gene therapy study. https://www.biopharmadive.com/news/astellas-gene-therapy-trial-death-fourth-audentes/606508/, Sept 14, 2021. (Accessed 12 January 2022)
Chand, DH, Zaidman, C, Arya, K, et al. Thrombotic microangiopathy following onasemnogene abeparvovec for spinal muscular atrophy: a case series. J Pediatr 231 (2021), 265–268.
Dangouloff, T, Servais, L, Clinical evidence supporting early treatment of patients with spinal muscular atrophy: current perspectives. Ther Clin Risk Manag 15 (2019), 1153–1161.
Sturdy, S, Miller, F, Hogarth, S, et al. Half a century of Wilson & Jungner: reflections on the governance of population screening. Wellcome Open Res, 5, 2020, 158.
Beckers, P, Caberg, J-H, Dideberg, V, et al. Newborn screening of Duchenne muscular dystrophy specifically targeting deletions amenable to exon-skipping therapy. Sci Rep, 11, 2021, 3011.
Peccate, C, Mollard, A, Le Hir, M, et al. Antisense pre-treatment increases gene therapy efficacy in dystrophic muscles. Hum Mol Genet 25 (2016), 3555–3563.
Markati, T, De Waele, L, Schara-Schmidt, U, et al. Lessons learned from discontinued clinical developments in Duchenne muscular dystrophy. Front Pharmacol, 12, 2021, 735912.
Aartsma-Rus, A, Goemans, N, A sequel to the eteplirsen saga: eteplirsen is approved in the United States but was not approved in Europe. Nucleic Acid Ther 29 (2019), 13–15.
Waddell, LB, Bryen, SJ, Cummings, BB, et al. WGS and RNA studies diagnose noncoding DMD variants in males with high creatine kinase. Neurol Genet, 7, 2021, e554.
de Feraudy, Y, Ben Yaou, R, Wahbi, K, et al. Very low residual dystrophin quantity is associated with milder dystrophinopathy. Ann Neurol 89 (2021), 280–292.
Ropars, J, Gravot, F, Ben Salem, D, Rousseau, F, Brochard, S, Pons, C, Muscle MRI: a biomarker of disease severity in Duchenne muscular dystrophy? A systematic review. Neurology 94 (2020), 117–133.
Servais, L, Yen, K, Guridi, M, et al. Stride velocity 95th centile: insights into gaining regulatory qualification of the first wearable-derived digital endpoint for use in Duchenne muscular dystrophy trials. Neuromuscul Disord 9 (2022), 335–346.
Poleur, M, Ulinici, A, Daron, A, et al. Normative data on spontaneous stride velocity, stride length, and walking activity in a non-controlled environment. Orphanet J Rare Dis, 16, 2021, 318.
Spitali, P, Zaharieva, I, Bohringer, S, et al. TCTEX1D1 is a genetic modifier of disease progression in Duchenne muscular dystrophy. Eur J Hum Genet EJHG 28 (2020), 815–825.
Weiss, RB, Vieland, VJ, Dunn, DM, Kaminoh, Y, Flanigan, KM, United Dystrophinopathy Project. Long-range genomic regulators of THBS1 and LTBP4 modify disease severity in Duchenne muscular dystrophy. Ann Neurol 84 (2018), 234–245.
Muntoni, F, Domingos, J, Manzur, AY, et al. Categorising trajectories and individual item changes of the North Star Ambulatory Assessment in patients with Duchenne muscular dystrophy. PloS One, 14, 2019, e0221097.
Goemans, N, Signorovitch, J, Sajeev, G, et al. Suitability of external controls for drug evaluation in Duchenne muscular dystrophy. Neurology 95 (2020), e1381–e1391.
Fouarge, E, Monseur, A, Boulanger, B, et al. Hierarchical Bayesian modelling of disease progression to inform clinical trial design in centronuclear myopathy. Orphanet J Rare Dis, 16, 2021, 3.
Mareedu, S, Million, ED, Duan, D, Babu, GJ, Abnormal calcium handling in Duchenne muscular dystrophy: mechanisms and potential therapies. Front Physiol, 12, 2021, 647010.
Fallon, JR, McNally, EM, Non-glycanated biglycan and LTBP4: leveraging the extracellular matrix for Duchenne muscular dystrophy therapeutics. Matrix Biol 68–69 (2018), 616–627.
