Recalibrating Therapeutic Priorities for Duchenne Muscular Dystrophy: A Critical Synthesis of Approved and Emerging Strategies Through the Lens of an Underrepresented Population.

BACKGROUND: Duchenne muscular dystrophy (DMD) has, for the first time, several mutation-specific drugs in clinical use. Four exon-skipping antisense oligonucleotides and one adeno-associated virus (AAV) micro-dystrophin gene therapy carry US FDA approval, and one nonsense-readthrough agent (ataluren) holds a conditional European authorisation that has since been placed under review; ataluren has never been approved by the FDA. Regulatory approval, however, has not translated cleanly into demonstrable clinical benefit, and in resource-limited settings it has not translated into access at all.

METHODS: We compiled published efficacy estimates for each approved therapy: the EMBARK randomised trial for delandistrogene moxeparvovec (Elevidys), the STRIDE registry for ataluren, and the long-term extension studies of eteplirsen, golodirsen, viltolarsen and casimersen. We read these alongside mutation-spectrum and clinical data from a Kazakh DMD cohort (n = 34), one of the first Central Asian populations to be characterised systematically. Because these sources differ in design, population, endpoint and follow-up, the comparison is indirect and descriptive rather than pooled or statistical. On that basis we assembled three descriptive maps: biological versus clinical efficacy, eligibility versus access, and an order-of-magnitude estimate of cost per year of preserved ambulation.

RESULTS: Across the approved therapies, larger biological dystrophin restoration did not correspond to longer preservation of walking. We describe this as the absence of the expected positive association rather than as evidence of a negative one: the comparison rests on a small number of drugs whose values come from heterogeneous studies. We did not-and with these data could not-test it as a formal correlation. Ataluren, with roughly 2% dystrophin restoration, was associated with a longer reported delay in loss of ambulation than Elevidys, which restores 34-51% micro-dystrophin. In the Kazakh cohort, 26.5% of patients were biologically eligible for exon-skipping and 11.8% for ataluren, yet realistic access to any mutation-specific therapy was effectively zero as of April 2026. Our order-of-magnitude cost estimates ran from about $12,000 per additional year of ambulation for standard of care to about $1.3 million for AAV gene therapy, a hundredfold range that did not track clinical effect.

CONCLUSIONS: We argue that the conventional priority ordering (gene therapy first, exon-skipping second, standard care as background) does not hold up when weighed against patient-relevant outcomes and cost, and may reasonably be inverted for resource-limited systems. This is our interpretation of an indirect comparison, not an evidence-based clinical recommendation. On that reading, the highest-value investments for Central Asia are early molecular diagnosis, universal access to glucocorticoids and specialised physiotherapy, and individual-import pathways for ataluren, while AAV gene therapy is, in our view, a lower near-term priority until its durability and safety data improve.