01At a glance
02What it is
Duchenne muscular dystrophy is the most common childhood muscular dystrophy, an X-linked disorder caused by dystrophin deficiency. Boys develop progressive muscle weakness from early childhood, losing ambulation in their teens and dying from respiratory or cardiac failure in young adulthood. Gene therapy and exon-skipping are the leading disease-modifying approaches.
03What goes wrong
Loss-of-function. Mutations in DMD abolish dystrophin, a large cytoskeletal protein that links the muscle fibre cytoskeleton to the extracellular matrix. Without dystrophin, muscle membranes are fragile and progressively degenerate, replaced by fibrosis and fat. This is a pure loss-of-function disease.
04How NIGHTINGALE routes it
Recommended modality: gene therapy (micro-dystrophin) + exon skipping
NOT eligible. DMD is a loss-of-function disease — dystrophin is absent, not accumulated. Degrading any residual/truncated dystrophin would worsen the disease. Correct routes are dystrophin restoration: gene therapy (micro-dystrophin), exon skipping (to restore reading frame), and stop-codon readthrough.
05Treatment today
Deflazacort (Emflaza)
2017-02-09Corticosteroid that slows muscle degeneration by reducing inflammation; prolongs ambulation by several years. Does NOT restore dystrophin.
06In the pipeline
- Gene therapy: delandistrogene moxeparvovec (Elevidys) — AAV micro-dystrophin (FDA accelerated approval 2023)
- Exon-skipping ASOs: eteplirsen (exon 51), golodirsen (53), casimersen (45), viltolarsen (53)
- Stop-codon readthrough: ataluren (translarna) — conditional approval in EU
- Utrophin upregulation (compensatory dystrophin homologue)
Key reference: PMID 3282674 · PubMed
07Verification
Every line below is the registry's own verification record — what was checked, against which source, and what is still open.
- uniprot: P11532 = DMD (Dystrophin), 3685 aa — VERIFIED via UniProt REST API (live)
- gene mutation: DMD gene loss-of-function mutations (out-of-frame deletions/duplications/nonsense) — VERIFIED (Nature Reviews Disease Primers 2021)
- inheritance: X-linked recessive — VERIFIED (OMIM 310200; Orphanet)
- orpha code: 98896 = Duchenne muscular dystrophy (Active) — VERIFIED via Orphanet API (live, 2026-07-02)
- drug mw: 441.5 Da, CID 189821, C25H31NO6 — VERIFIED via PubChem REST API (live)
- fda date: Deflazacort 2017-02-09; Elevidys (gene therapy) 2023 — commonly cited; exact NDA not re-verified this session
08Sources
| Fact | Source | Accession | Retrieved |
|---|---|---|---|
| Gene/protein identity | UniProt | P11532 (DMD, Dystrophin, 3685 aa) | 2026-10-04 |
| Disease classification & definition | Orphanet | ORPHAcode 98896 (Duchenne muscular dystrophy) | 2026-10-04 |
| Inheritance & genetics | OMIM | 310200 (Duchenne Muscular Dystrophy) | 2026-10-04 |
| Drug molecular weight | PubChem | CID 189821 (deflazacort, 441.5 Da, C25H31NO6) | 2026-10-04 |
| Disease mechanism | Nature Reviews Disease Primers 2021 | Duchenne muscular dystrophy (s41572-021-00248-3) | 2026-10-04 |
Corrections carried into registry v2 (3)
- VERIFIED (2026-10-04): built fresh. ORPHAcode 98896 confirmed live via Orphanet API.
- CLARIFIED: deflazacort is SYMPTOMATIC (anti-inflammatory), not disease-modifying — the disease-modifying route is gene therapy / exon skipping, now correctly listed as investigational.
- CLARIFIED: DMD is pure loss-of-function — NOT AUTOTAC eligible. Prior data marked DMD 'CLIN-RDY' without explaining the mechanism-gate decision.