The Treatment of Duchenne Muscular Dystrophy: From Supportive Care to Gene Therapy Innovations

Duchenne Muscular Dystrophy (DMD) is a severe, progressive genetic disorder that primarily affects young boys, leading to muscle weakness, loss of ambulation, and ultimately respiratory and cardiac failure. Caused by mutations in the dystrophin gene on the X chromosome, DMD results in the absence or dysfunction of dystrophin, a protein essential for maintaining muscle cell integrity. Affecting approximately 1 in 5,000 male births worldwide, the condition typically manifests in early childhood with symptoms like delayed walking, frequent falls, and difficulty rising from the floor. Without intervention, most individuals lose the ability to walk by their early teens and face a shortened lifespan, often into the late 20s or early 30s due to complications. While there is no cure, treatments have evolved significantly over the past decade, shifting from purely symptomatic management to targeted molecular therapies. This essay explores the current landscape of DMD treatments, including supportive care, pharmacological interventions, gene therapies, and emerging approaches, highlighting advancements as of 2025.

Historically, DMD treatment focused on supportive measures to improve quality of life and delay progression. Multidisciplinary care remains the cornerstone, involving a team of specialists such as neurologists, cardiologists, pulmonologists, physical therapists, and nutritionists. Physical and occupational therapy help maintain mobility, prevent contractures, and promote independence through exercises, orthotics, and assistive devices like wheelchairs. Respiratory support, including non-invasive ventilation like BiPAP machines, addresses weakening diaphragm muscles, while cardiac monitoring and medications like ACE inhibitors or beta-blockers manage cardiomyopathy, a common cause of mortality in DMD. Nutritional interventions, such as high-calorie diets or gastrostomy tubes, combat weight loss from swallowing difficulties. These supportive strategies, while not altering the disease's genetic basis, can extend ambulation by 1-3 years and improve survival rates.

Pharmacological treatments have advanced with corticosteroids as the first-line option since the 1990s. Drugs like prednisone and deflazacort reduce inflammation, stabilize muscle membranes, and slow muscle degeneration, potentially delaying loss of ambulation by 2-5 years. However, long-term use is associated with side effects including weight gain, osteoporosis, and behavioral changes. In response, vamorolone (Agamree), a novel steroid analogue, was approved by the FDA in 2023 and by Health Canada in October 2025, offering similar efficacy with reduced adverse effects on bone health and growth. Clinical trials showed vamorolone preserves muscle strength comparable to traditional steroids but with fewer instances of stunted growth, making it a preferred choice for younger patients.

A major breakthrough in DMD treatment came with the advent of targeted therapies addressing the underlying genetic defect. Exon skipping drugs represent a personalized approach for patients with specific amenable mutations, which account for about 30-40% of cases. These antisense oligonucleotides "skip" faulty exons during mRNA processing, allowing production of a truncated but functional dystrophin protein, akin to the milder Becker muscular dystrophy. FDA-approved options include eteplirsen (Exondys 51) for exon 51 mutations (2016), golodirsen (Vyondys 53) and viltolarsen (Viltepso) for exon 53 (2019 and 2020), and casimersen (Amondys 45) for exon 45 (2021). Administered via weekly intravenous infusions, these therapies have demonstrated modest increases in dystrophin levels (1-5%) and stabilized motor function in trials, though long-term benefits vary. Critics note the high cost—over $300,000 annually per patient—and the need for mutation-specific matching, limiting accessibility.

Gene therapy has revolutionized DMD management by directly delivering functional dystrophin genes. The first approved gene therapy, delandistrogene moxeparvovec (Elevidys), received FDA accelerated approval in June 2023 for ambulatory children aged 4-5 with confirmed DMD mutations. This one-time intravenous infusion uses an adeno-associated virus (AAV) vector to introduce a "micro-dystrophin" gene—a shortened version of the massive dystrophin gene that fits within viral delivery limits. Real-world data from 2025 indicates improved muscle function and reduced creatine kinase levels in treated patients, with sustained benefits observed up to two years post-treatment. However, challenges include immune responses to the AAV vector, potential liver toxicity, and exclusion of patients with pre-existing antibodies to the virus, affecting about 20-30% of candidates. In 2025, the FDA expanded Elevidys' label based on ongoing trials, and real-world experience reports highlight its role in slowing progression, though not reversing damage.

Beyond gene replacement, other molecular therapies have gained traction. Givinostat (Duvyzat), a histone deacetylase inhibitor, was approved by the FDA in 2024 to reduce inflammation and fibrosis while promoting muscle regeneration. Taken orally twice daily, it complements steroids and has shown in phase 3 trials to improve upper limb function and delay functional decline in ambulatory boys. Emerging in 2025, delpacibart zotadirsen (del-zota), an antibody-oligonucleotide conjugate, received FDA Breakthrough Therapy designation for enhanced exon skipping efficiency, potentially benefiting a broader mutation spectrum.

Looking ahead, emerging therapies promise to address DMD's root causes more comprehensively. Next-generation gene therapies aim to overcome current limitations, such as developing better AAV vectors for larger gene payloads or redosing capabilities. Precision BioSciences' PBGENE-DMD, highlighted in July 2025 preclinical data, uses in vivo gene editing to restore full-length dystrophin, showing improved muscle function in animal models. CRISPR-Cas9 gene editing is in early clinical stages, with trials editing out mutations directly in muscle cells, potentially applicable to 45% of patients as per a 2025 University of Alberta study. Stem cell therapies, involving transplantation of muscle progenitor cells, are advancing, with phase 1/2 trials demonstrating safety and preliminary efficacy in regenerating muscle tissue. Other pipelines include myostatin inhibitors to enhance muscle growth, utrophin upregulators as dystrophin substitutes, and anti-inflammatory agents like those from Santhera Pharmaceuticals.

Despite progress, challenges persist. High costs—Elevidys exceeds $3 million per dose—limit access, exacerbating disparities in global healthcare. Immune rejection, off-target effects in gene editing, and the need for early intervention before irreversible damage complicate therapies. Moreover, DMD's heterogeneity requires personalized approaches, and long-term data on newer treatments is still emerging. As of 2025, no therapy fully restores dystrophin or halts progression entirely, underscoring the need for combination regimens.

Duchenne Muscular Dystrophy treatment has transformed from palliative care to innovative genetic interventions, offering hope for prolonged ambulation and better quality of life. With approvals like vamorolone and givinostat, and gene therapies like Elevidys paving the way, the field is poised for further breakthroughs via CRISPR and advanced vectors. Continued research, equitable access, and multidisciplinary support are crucial to turning these advancements into widespread victories against Duchenne Muscular Dystrophy, potentially extending lives and restoring function for affected individuals.