pediatrics
Duchenne Muscular Dystrophy and Becker Muscular Dystrophy
Treatment
Supportive measures Sometimes corrective surgery Sometimes, for cardiomyopathy, an angiotensin-converting enzyme inhibitor and/or beta-blocker For Duchenne dystrophy,prednisoneordeflazacortand sometimes genetic therapy Treatment involves a multidisciplinary approach that includes both nonpharmacologic and pharmacologic measures, which include genetic therapies. Gentle (ie, submaximal) active exercise is encouraged for as long as possible to avoid disuse atrophy or complications of inactivity. Passive exercises may extend the period of ambulation. Orthopedic interventions should be aimed at maintaining function and preventing contractures. Ankle-foot orthoses worn during sleep may help prevent flexion contractures. Leg braces may temporarily help preserve ambulation or standing. Corrective surgery is sometimes needed, particularly for scoliosis. Obesity should be avoided; caloric requirements are likely to be less than normal because of decreased physical activity. Respiratory insufficiency may be treated with noninvasive ventilatory support (eg, Status asthmaticus ) and sometimes with mechanical ventilation. Elective tracheotomy is gaining acceptance, allowing children with Duchenne dystrophy to live into their 30s and beyond. For children with Dilated Cardiomyopathy , an angiotensin-converting enzyme inhibitor and/or a beta-blocker may help prevent or slow progression ( Investigational therapies for Duchenne dystrophy and Becker dystrophy include gene therapy, creatine, myostatin inactivation, skeletal muscle progenitors, and the antioxidant idebenone ( Treatment references ). Prenatal Genetic Counseling is indicated. ) are the mainstay of therapy for patients > age 4 years who are no longer gaining or have declining motor skills ( Treatment references ). Corticosteroids start working as early as 10 days after initiation of therapy; efficacy peaks at 3 months and persists for 6 months. Long-term use improves strength, delays the age at which ambulation is lost by 1.4 to 2.5 years, improves timed function testing (a measurement of how fast a child completes a functional task, such as walking or getting up from the floor), improves pulmonary function, reduces orthopedic complications (eg, the need for scoliosis surgery), stabilizes cardiac function (eg, delays onset of cardiomyopathy until 18 years of age), and increases survival by 5 to 15 years ( Deflazacortmay be associated with a greater risk of cataracts thanprednisone. Use ofprednisoneordeflazacortin Becker dystrophy has not been adequately studied. Genetic therapies that increase dystrophin levels are available in some countries, but they are costly and their benefit is uncertain ( Treatment references ). The use of these therapies requires careful consideration and shared-decision making. Exon-skipping medications(IVeteplirsen,golodirsen,viltolarsen, andcasimersen) use antisense oligonucleotides that work like molecular patches to the abnormaldystrophingene in which 1 or more exons are missing (the missing exons prevent the full protein from being assembled thus causing severe symptoms). These medications mask an exon so that it will be skipped and ignored during protein production, allowing for the production of a dystrophin protein that, although not normal, is functional and theoretically lessens symptoms so that patients function more like boys with the less severe Becker muscular dystrophy. gene mutation that is amenable to exon 51 skipping. The medication's approval has been criticized because it was based on a small trial that relied on a surrogate outcome (dystrophin in muscle biopsy) ( Treatment references ), and clinical benefit remains unproved. Golodirsenandviltolarsenskip exon 53. They can be used in the 8% of patients with Duchenne dystrophy who have a mutation in thedystrophingene amenable to exon 53 skipping. Clinical benefit remains unproved. Casimersenskips exon 45. It can be used in the 8% of patients with Duchenne dystrophy with a confirmed mutation amenable to exon 45 skipping. It increases dystrophin production, but clinical benefit has not been shown. Stop codon read-through medications(eg, oralataluren[PTC124]) bypass premature stop codons, allowing for the production of a functional protein. Stop codons are nonsense mutations that stop the production of a functioning protein too early, resulting in a truncated, nonfunctional protein. is available in the European Union and United Kingdom. Clinical benefit is unproved ( Treatment references ). Gene transfer via viral vectors(eg,delandistrogene moxeparvovec) use viral vectors to deliver corrective genetic material to the affected muscles. is the only agent approved for gene transfer therapy via viral vector, whereby microdystrophin transgenes can be delivered to skeletal and cardiac muscle using an adeno-associated virus capsid (AAVrh74). No functional improvement was seen in the trial ( Treatment references ), but in a subgroup analysis, some improvement in functional status was seen in the 4- to 5-year-old age group ( 1.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 Neurol17(4):347-361, 2018. doi: 10.1016/S1474-4422(18)30025-5 2.Ren S, Yao C, Liu Y, et al: Antioxidants for Treatment of Duchenne Muscular Dystrophy: A Systematic Review and Meta-Analysis.Eur Neurol85(5):377-388, 2022. doi: 10.1159/000525045 3.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.Neurology86:465–472, 2016. doi: 10.1212/WNL.0000000000002337 4.Bendicksen L, Zuckerman DM, Avorn J, et al: The Regulatory Repercussions of Approving Muscular Dystrophy Medications on the Basis of Limited Evidence.Ann Intern Med176(9):1251-1256, 2023. doi: 10.7326/M23-1073 5.Mendell JR, Goemans N, Lowes LP, et al: Longitudinal effect ofeteplirsenversus historical control on ambulation in Duchenne muscular dystrophy.Ann Neurol79(2):257-271, 2016. doi: 10.1002/ana.24555 6.McDonald CM, Campbell C, Torricelli RE, et al:Atalurenin patients with nonsense mutation Duchenne muscular dystrophy (ACT DMD): A multicentre, randomised, double-blind, placebo-controlled, phase 3 trial.Lancet390:(10101):1489–1498, 2017. doi: 10.1016/S0140-6736(17)31611-2 7.Mendell JR, Shieh PB, McDonald CM, et al: Expression of SRP-9001 dystrophin and stabilization of motor function up to 2 years post-treatment withdelandistrogene moxeparvovecgene therapy in individuals with Duchenne muscular dystrophy.Front Cell Dev Biol11:1167762, 2023. doi: 10.3389/fcell.2023.1167762 8.Elevidys.Prescribing information. Sarepta Therapeutics, Inc; 2023. Accessed January 9, 2024. 