{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T17:03:36Z","timestamp":1784653416873,"version":"3.55.0"},"reference-count":15,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>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\u2014and with these data could not\u2014test 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\u201351% 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.<\/jats:p>","DOI":"10.3390\/genes17070826","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T16:19:27Z","timestamp":1784564367000},"page":"826","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Recalibrating Therapeutic Priorities for Duchenne Muscular Dystrophy: A Critical Synthesis of Approved and Emerging Strategies Through the Lens of an Underrepresented Population"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7770-8427","authenticated-orcid":false,"given":"Saken","family":"Khaidarov","sequence":"first","affiliation":[{"name":"Department of Molecular Biology and Medical Genetics, Asfendiyarov Kazakh National Medical University, Zheltoksan Street 37A, Almaty 050004, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0186-978X","authenticated-orcid":false,"given":"Aizhan","family":"Moldakaryzova","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Medical Genetics, Asfendiyarov Kazakh National Medical University, Zheltoksan Street 37A, Almaty 050004, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dias","family":"Dautov","sequence":"additional","affiliation":[{"name":"Centre for Orphan Diseases with Neurological Manifestations, Republican Children\u2019s Clinical Hospital \u201cAksai\u201d, Almaty 050067, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nurgul","family":"Sagatbayeva","sequence":"additional","affiliation":[{"name":"Department of Propaedeutics of Childhood Diseases, Children\u2019s City Clinical Hospital No. 2, Asfendiyarov Kazakh National Medical University, Tole-Bi Street 94, Almaty 050012, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Banu","family":"Yeszhan","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Physiology and Sports Medicine, Kazakh Academy of Sport and Tourism, Abay 85, Almaty 050022, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2555-8644","authenticated-orcid":false,"given":"Bayan","family":"Nurgaliyeva","sequence":"additional","affiliation":[{"name":"Department of Propaedeutics of Internal Medicine, Kazakh National Medical University Named After S.D. Asfendiyarov, Tole-Bi Street 94, Almaty 050012, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-7612-5428","authenticated-orcid":false,"given":"Saltanat","family":"Kenbayeva","sequence":"additional","affiliation":[{"name":"Department of Normal Anatomy, Asfendiyarov Kazakh National Medical University, Almaty 050000, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gulban","family":"Abdullayeva","sequence":"additional","affiliation":[{"name":"Department of Propaedeutics of Childhood Diseases, Children\u2019s City Clinical Hospital No. 2, Asfendiyarov Kazakh National Medical University, Tole-Bi Street 94, Almaty 050012, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marat","family":"Rabandiyarov","sequence":"additional","affiliation":[{"name":"Department of Propaedeutics of Childhood Diseases, Children\u2019s City Clinical Hospital No. 2, Asfendiyarov Kazakh National Medical University, Tole-Bi Street 94, Almaty 050012, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karlygash N.","family":"Tazhibayeva","sequence":"additional","affiliation":[{"name":"Department of Surgery, Faculty of Medicine and Health, Al-Farabi Kazakh National University, Al-Farabi Street 71, Almaty 050040, Kazakhstan"},{"name":"Almaty Regional Multidisciplinary Clinic, Ministry of Health of the Republic of Kazakhstan, Al-Farabi Street 71, Almaty 050040, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4662-0817","authenticated-orcid":false,"given":"Assel","family":"Sadykova","sequence":"additional","affiliation":[{"name":"Department of General Medical Practice, School of Medicine and Healthcare, Al-Farabi University, Al-Farabi Street 71, Almaty 050040, Kazakhstan"},{"name":"National Scientific Centre of Phthisiopulmonology, Ministry of Health of The Republic of Kazakhstan 5 Bekkhozhin street, Almaty 050010, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aibek","family":"Yermekbay","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Resuscitation, Asfendiyarov Kazakh National Medical University, Tole-Bi Street 94, Almaty 050012, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5081-1264","authenticated-orcid":false,"given":"Askar","family":"Aidarov","sequence":"additional","affiliation":[{"name":"Department of Oncology, Kazakh-Russian Medical University, Almaty 050012, Kazakhstan"},{"name":"Department of Oncology, Asfendiyarov Kazakh National Medical University, Tole-Bi Street 94, Almaty 050012, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daulet","family":"Aidarov","sequence":"additional","affiliation":[{"name":"Department of Oncology, Kazakh-Russian Medical University, Almaty 050012, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aray","family":"Aidarova","sequence":"additional","affiliation":[{"name":"Department of Public Health, Kazakh-Russian Medical University, Abylay Khan Avenue 51\/53, Almaty 050040, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saniyam","family":"Kurbaniyazova","sequence":"additional","affiliation":[{"name":"Department of Normal Anatomy, Asfendiyarov Kazakh National Medical University, Almaty 050000, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nazym","family":"Abiyrova","sequence":"additional","affiliation":[{"name":"Department of Normal Anatomy, Asfendiyarov Kazakh National Medical University, Almaty 050000, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2112-4208","authenticated-orcid":false,"given":"Mukhit","family":"Kulmaganbetov","sequence":"additional","affiliation":[{"name":"Centre for Eye and Vision Research, Room 901\u2013903, 17W, Hong Kong Science Park, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/0888-7543(88)90113-9","article-title":"An explanation for the phenotypic differences between patients bearing partial deletions of the DMD locus","volume":"2","author":"Monaco","year":"1988","journal-title":"Genomics"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1089\/nat.2017.0682","article-title":"Development of exon skipping therapies for Duchenne muscular dystrophy: A critical review and a perspective on the outstanding issues","volume":"27","author":"Straub","year":"2017","journal-title":"Nucleic Acid. 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Mutat."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/17\/7\/826\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T16:21:37Z","timestamp":1784650897000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/17\/7\/826"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,20]]},"references-count":15,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["genes17070826"],"URL":"https:\/\/doi.org\/10.3390\/genes17070826","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,20]]}}}