Recent Updates in Duchenne Muscular Dystrophy Treatment
The most significant recent advances in DMD treatment include FDA-approved exon-skipping antisense oligonucleotides (eteplirsen for exon 51, golodirsen for exon 53), gene replacement therapy with micro-dystrophin, and refined cardiac management protocols emphasizing early ACE inhibitor/beta-blocker initiation with cardiac MRI surveillance. 1, 2, 3, 4
Genetic-Based Therapies
Exon-Skipping Antisense Oligonucleotides
FDA-approved exon-skipping therapies now provide mutation-specific treatment options for approximately 13% of DMD patients amenable to exon 51 skipping and 8% amenable to exon 53 skipping. 2, 3, 5
Eteplirsen (EXONDYS 51) is approved for patients with confirmed DMD gene mutations amenable to exon 51 skipping, dosed at 30 mg/kg once weekly as an intravenous infusion over 35-60 minutes via 0.2 micron in-line filter 2
Golodirsen (VYONDYS 53) is approved for exon 53 skipping at the same dosing regimen (30 mg/kg weekly IV), but requires baseline monitoring of serum cystatin C, urine dipstick, and urine protein-to-creatinine ratio before initiation due to potential kidney toxicity 3
Both therapies received accelerated FDA approval based on increased dystrophin production in skeletal muscle, though continued approval depends on verification of clinical benefit in confirmatory trials 2, 3
Common adverse reactions include balance disorder and vomiting for eteplirsen (≥35% incidence), and headache, pyrexia, fall, abdominal pain, and nasopharyngitis for golodirsen (≥20% incidence) 2, 3
A critical caveat: hypersensitivity reactions including bronchospasm, chest pain, anaphylaxis, and urticaria can occur with both agents, requiring immediate medical intervention and consideration of slowing/interrupting infusion. 2, 3
Gene Replacement Therapy
Micro-dystrophin gene therapy using adeno-associated virus vectors represents the newest therapeutic class, with recent FDA approval of Elevidys marking a paradigm shift toward gene transfer approaches 6, 4
Gene therapy aims to deliver a truncated but functional dystrophin gene to restore protein expression throughout affected muscles 7, 4
Multiple gene therapy candidates are advancing through Phase I trials, though safety and efficacy profiles are still being established at this early developmental stage 6
Emerging Gene Editing Approaches
- CRISPR-based gene editing technologies are under investigation to permanently correct DMD mutations, though these remain in preclinical and early clinical development 7, 4
Pharmacological Management Updates
Glucocorticoid Therapy
Prednisone/prednisolone at 0.75 mg/kg daily or deflazacort at 0.9 mg/kg daily remain the only medications proven to slow decline in muscle strength and function, and should be initiated early to prevent faster disease progression. 1
Close monitoring for glucocorticoid side effects is mandatory, including weight gain, behavioral changes, bone health deterioration, and growth suppression 1
Delaying glucocorticoid initiation accelerates disease progression—early implementation is critical 1
Cardiac Management Advances
Updated cardiac surveillance protocols now emphasize cardiac MRI (CMR) as the preferred imaging modality over echocardiography alone, with recommendations for CMR inclusion in all Phase II/III muscle therapy trials. 8
Echocardiogram should be performed at diagnosis or by age 6 years, with follow-up at least every 24 months 1
Early intervention with ACE inhibitors and beta-blockers is recommended at first signs of cardiac dysfunction, before overt cardiomyopathy develops 1
Mineralocorticoid receptor antagonists are now included in medical management recommendations alongside ACE inhibitors and angiotensin receptor blockers 8
Cardiac surveillance using CMR provides superior detection of early myocardial changes compared to echocardiography, allowing earlier therapeutic intervention 8
A major pitfall: cardiomyopathy remains underdiagnosed and undertreated in DMD patients despite broader appreciation of its impact on mortality—aggressive cardiac management is essential. 8
Multidisciplinary Care Coordination
Functional Monitoring
Muscle strength assessment using manual muscle testing and quantitative myometry every 6 months during ambulatory phase 1
Timed function tests including 10-meter walk, timed Gowers' maneuver, 4-stair climb, rise from chair, and 6-minute walk test 1
Range of motion monitoring with goniometry focusing on hip, knee, ankle joints, iliotibial band, hamstrings, and gastrocnemius 1
Orthopedic Interventions
Ankle-foot orthoses should be prescribed when ankle dorsiflexion weakness develops to prolong ambulation 1
Surgical intervention for iliotibial band lengthening or Achilles tendon release when contractures limit function 1
Psychosocial Support
Comprehensive neuropsychological assessment at diagnosis and before school entry to establish baseline cognitive function 1
Regular screening for depression, anxiety, obsessive-compulsive disorder, and attention-deficit hyperactivity disorder 1
Selective serotonin reuptake inhibitors for moderate to severe depression, anxiety, or OCD 1
Stimulants for ADHD following standard guidelines with cardiac monitoring 1
Mood stabilizers for aggression and emotional dysregulation 1
Care Coordination Infrastructure
Designated care coordinator with sufficient DMD clinical training to serve as family's point of contact, schedule appointments, and facilitate communication between clinicians 1
Transition planning for adolescents moving to adult care, encouraging self-advocacy and developing educational/vocational opportunities 1
Research Infrastructure Developments
International collaborative efforts are establishing standardized biorepositories, registries, and consensus-based protocols to accelerate DMD research and improve data collection across clinical trials. 8
Development of registries to assist with standardized data collection and follow-up 8
Creation of biorepositories to centrally store DNA, cell, and tissue specimens 8
Refinement of standard operating procedures for DMD animal models using state-of-the-art cardiac imaging protocols 8
Critical Gaps and Future Directions
Optimal timing and strategies for early cardiac intervention to prevent disease progression remain under investigation 8
Risk stratification methods for arrhythmia complications and sudden cardiac death need refinement 8
The relationship between early pulmonary intervention and cardiac disease progression requires further study 8
Genotype-phenotype correlations using advanced sequencing combined with detailed cardiac phenotyping are being explored 8
Cardiac monitoring protocols for female carriers need standardization 8
The convergence of mutation-specific genetic therapies, improved cardiac surveillance with CMR, and coordinated multidisciplinary care represents a transformative shift in DMD management, with the potential to significantly improve survival and quality of life. 1, 4