Antioxidants for Treatment of Duchenne Muscular Dystrophy: A Systematic Review and Meta-Analysis

Clinical Neurology: Meta-Analysis

Ren S.a· Yao C.a· Liu Y.b· Feng G.b· Dong X.a· Gao B.a· Qian S.c

Author affiliations

aDepartment of Pediatrics, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
bCenter for Clinical Epidemiology and Evidence-based Medicine, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China
cPediatric Intensive Care Unit, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, China

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Article / Publication Details

First-Page Preview

Abstract of Clinical Neurology: Meta-Analysis

Received: September 03, 2021
Accepted: April 29, 2022
Published online: June 13, 2022

Number of Print Pages: 12
Number of Figures: 4
Number of Tables: 1

ISSN: 0014-3022 (Print)
eISSN: 1421-9913 (Online)

For additional information: https://www.karger.com/ENE

Abstract

Introduction: Increasing evidence has shown that oxidative stress is involved in the pathogenesis of Duchenne muscular dystrophy (DMD). Oxidative stress impairs muscle function, reduces regenerative capacity, and leads to atrophy and muscle weakness. The present study aimed to evaluate the effectiveness and safety of antioxidants in treatment of DMD patients. Methods: Medline, Embase, EBSCOhost, and Cochrane Library databases were searched using relevant keywords regarding DMD and antioxidants. The risk of bias for all included studies was assessed using the Cochrane risk of bias tool. The effectiveness of antioxidants in improving pulmonary function and muscle strength in DMD patients and their rate of adverse events was evaluated by meta-analysis. Results: A total of nine eligible studies were identified. Among these, two studies involving 85 patients compared idebenone with placebo. Pooled data showed a significant improvement in pulmonary function after idebenone treatment. Flavonoids- and omega 3-based compounds (FLAVOMEGA) significantly improved muscle strength. Two studies evaluated coenzyme Q10 (CoQ10) and reported clinical improvement in physical activity. The remaining four studies evaluated pentoxifylline, superoxide dismutase, vitamin E combination with penicillamine and penicillamine alone, respectively, and found no significant differences between the intervention and placebo groups, measured by pulmonary function, muscle strength, movement function, or quality of life. Most adverse events were mild, while the rates of dropout and serious adverse events were low with respect to antioxidants. Conclusions: Idebenone appeared to be safe and effective in improving pulmonary function in DMD patients, while pentoxifylline, superoxide dismutase, penicillamine, or a combination of vitamin E with penicillamine did not show a significant therapeutic effect. CoQ10 and FLAVOMEGA might be beneficial in improving muscle strength or physical activity in DMD patients. However, additional trials with more participants are warranted in the future.

© 2022 S. Karger AG, Basel

References 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. 2016 Jan;96(1):253–305. Spencer MJ, Tidball JG. Do immune cells promote the pathology of dystrophin-deficient myopathies? Neuromuscul Disord. 2001 Sep;11(6–7):556–64. Evans NP, Misyak SA, Robertson JL, Bassaganya-Riera J, Grange RW. Immune-mediated mechanisms potentially regulate the disease time-course of duchenne muscular dystrophy and provide targets for therapeutic intervention. PM R. 2009 Aug;1(8):755–68. 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 Oct;50(4):477–87. 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 Sep;390(10101):1489–98. 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 Feb;79(2):257–71. 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 Mar;17(3):251–67. Leigh F, Ferlini A, Biggar D, Bushby K, Finkel R, Morgenroth LP, et al. Neurology care, diagnostics, and emerging therapies of the patient with Duchenne muscular dystrophy. Pediatrics. 2018 Oct;142(Suppl 2):S5–16. Falzarano MS, Scotton C, Passarelli C, Ferlini A. Duchenne muscular dystrophy: from diagnosis to therapy. Molecules. 2015 Oct;20(10):18168–84. Huizenga NA, Koper JW, De Lange P, Pols HA, Stolk RP, Burger H, et al. A polymorphism in the glucocorticoid receptor gene may be associated with and increased sensitivity to glucocorticoids in vivo. J Clin Endocrinol Metab. 1998 Jan;83:144–51. Whitehead NP, Yeung EW, Allen DG. Muscle damage in mdx (dystrophic) mice: role of calcium and reactive oxygen species. Clin Exp Pharmacol Physiol. 2006 Jul;33(7):657–62. McConell GK, Wadley GD. Potential role of nitric oxide in contraction-stimulated glucose uptake and mitochondrial biogenesis in skeletal muscle. Clin Exp Pharmacol Physiol. 2008 Dec;35(12):1488–92. Kim JH, Kwak HB, Thompson LV, Lawler JM. Contribution of oxidative stress to pathology in diaphragm and limb muscles with Duchenne muscular dystrophy. J Muscle Res Cell Motil. 2013 Feb;34(1):1–13. Roelofs RI, de Arango GS, Law PK, Kinsman D, Buchanan DC, Park JH. Treatment of Duchenne’s muscular dystrophy with penicillamine. Results of a double-blind trial. Arch Neurol. 1979 May;36(5):266–8. Stern LZ, Ringel SP, Ziter FA, Menander-Huber KB, Ionasescu V, Pellegrino RJ, et al. Drug trial of superoxide dismutase in Duchenne’s muscular dystrophy. Arch Neurol. 1982 Jun;39(6):342–6. Fenichel GM, Brooke MH, Griggs RC, Mendell JR, Miller JP, Moxley RT 3rd, et al. Clinical investigation in Duchenne muscular dystrophy: penicillamine and vitamin E. Muscle Nerve. 1988 Nov;11(11):1164–8. Folkers K, Simonsen R. Two successful double-blind trials with coenzyme Q10 (vitamin Q10) on muscular dystrophies and neurogenic atrophies. Biochim Biophys Acta. 1995 May;1271(1):281–6. Buyse GM, Goemans N, van den Hauwe M, Thijs D, de Groot IJ, Schara U, et al. Idebenone as a novel, therapeutic approach for Duchenne muscular dystrophy: results from a 12 month, double-blind, randomized placebo-controlled trial. Neuromuscul Disord. 2011 Jun;21(6):396–405. Escolar DM, Zimmerman A, Bertorini T, Clemens PR, Connolly AM, Mesa L, et al. Pentoxifylline as a rescue treatment for DMD: a randomized double-blind clinical trial. Neurology. 2012 Mar;78(12):904–13. Buyse GM, Voit T, Schara U, Straathof CSM, D’Angelo MG, Bernert G, 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. 2015 May;385(9979):1748–57. Sitzia C, Meregalli M, Belicchi M, Farini A, Arosio M, Bestetti D, et al. Preliminary evidences of safety and efficacy of flavonoids- and omega 3-based compound for muscular dystrophies treatment: a randomized double-blind placebo controlled pilot clinical trial. Front Neurol. 2019 Aug;10:755. Moher D, Shamseer L, Clarke M, Ghersi D, Liberati A, Petticrew M, et al. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst Rev. 2015 Jan;4(1):1. McDonald CM, Meier T, Voit T, Schara U, Straathof CS, D’Angelo MG, et al. Idebenone reduces respiratory complications in patients with Duchenne muscular dystrophy. Neuromuscul Disord. 2016 Aug;26(8):473–80. Buyse GM, Goemans N, van den Hauwe M, Meier T. Effects of glucocorticoids and idebenone on respiratory function in patients with duchenne muscular dystrophy. Pediatr Pulmonol. 2013 Sep;48(9):912–20. Buyse GM, Voit T, Schara U, Straathof CS, D’Angelo MG, Bernert G, et al. Treatment effect of idebenone on inspiratory function in patients with Duchenne muscular dystrophy. Pediatr Pulmonol. 2017 Apr;52(4):508–15. Mayer OH, Leinonen M, Rummey C, Meier T, Buyse GM. Efficacy of idebenone to preserve respiratory function above clinically meaningful thresholds for forced vital capacity (FVC) in patients with Duchenne muscular dystrophy. J Neuromuscul Dis. 2017 Sep;4(3):189–98. Servais L, Straathof CSM, Schara U, Klein A, Leinonen M, Hasham S, et al. Long-term data with idebenone on respiratory function outcomes in patients with Duchenne muscular dystrophy. Neuromuscul Disord. 2020 Jan;30(1):5–16. Burdi R, Rolland JF, Fraysse B, Litvinova K, Cozzoli A, Giannuzzi V, et al. Multiple pathological events in exercised dystrophic mdx mice are targeted by pentoxifylline: outcome of a large array of in vivo and ex vivo tests. J Appl Physiol. 2009 Apr;106(4):1311–24. Millis KK, Rabenstein DL. 1H-nuclear magnetic resonance study of the oxidation/reduction chemistry of penicillamine in intact human erythrocytes. Biochim Biophys Acta. 1990 Oct;1055(1):10–8. Spurney CF, Rocha CT, Henricson E, Florence J, Mayhew J, Gorni K, et al. CINRG pilot trial of coenzyme Q10 in steroid-treated Duchenne muscular dystrophy. Muscle Nerve. 2011 Aug;44(2):174–8. Dorchies OM, Wagner S, Vuadens O, Waldhauser K, Buetler TM, Kucera P, et al. Green tea extract and its major polyphenol (-)-epigallocatechin gallate improve muscle function in a mouse model for Duchenne muscular dystrophy. Am J Physiol Cell Physiol. 2006 Feb;290(2):C616–25. Buetler TM, Renard M, Offord EA, Schneider H, Ruegg UT. Green tea extract decreases muscle necrosis in mdx mice and protects against reactive oxygen species. Am J Clin Nutr. 2002 Apr;75(4):749–53. Hori YS, Kuno A, Hosoda R, Tanno M, Miura T, Shimamoto K, et al. Resveratrol ameliorates muscular pathology in the dystrophic mdx mouse, a model for Duchenne muscular dystrophy. J Pharmacol Exp Ther. 2011 Sep;338(3):784–94. Nakae Y, Dorchies OM, Stoward PJ, Zimmermann BF, Ritter C, Ruegg UT. Quantitative evaluation of the beneficial effects in the mdx mouse of epigallocatechin gallate, an antioxidant polyphenol from green tea. Histochem Cell Biol. 2012 Jun;137(6):811–27. Ljubicic V, Burt M, Lunde JA, Jasmin BJ. Resveratrol induces expression of the slow, oxidative phenotype in mdx mouse muscle together with enhanced activity of the SIRT1-PGC-1α axis. Am J Physiol Cell Physiol. 2014 Jul;307(1):C66–82. Article / Publication Details

First-Page Preview

Abstract of Clinical Neurology: Meta-Analysis

Received: September 03, 2021
Accepted: April 29, 2022
Published online: June 13, 2022

Number of Print Pages: 12
Number of Figures: 4
Number of Tables: 1

ISSN: 0014-3022 (Print)
eISSN: 1421-9913 (Online)

For additional information: https://www.karger.com/ENE

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