01At a glance
02What it is
Myotonic dystrophy type 1 is an autosomal dominant disorder caused by a CTG repeat expansion in DMPK, whose expanded CUG-repeat mRNA forms toxic nuclear foci that disrupt RNA splicing. It causes myotonia, progressive muscle weakness, cardiac conduction defects, and cataracts. Antisense therapy targeting the toxic RNA is the leading disease-modifying approach.
03What goes wrong
RNA toxicity (not protein toxicity). The expanded CUG repeat in DMPK mRNA forms nuclear foci that sequester RNA-binding proteins (e.g. MBNL1) and misregulate alternative splicing, causing myotonia, muscle weakness, cardiac conduction defects, and cataracts. The toxic species is the mutant RNA, not the protein.
04How NIGHTINGALE routes it
Recommended modality: aso (antisense to degrade the toxic CUG-repeat RNA)
NOT eligible (protein-level). The toxic species is the mutant DMPK mRNA (CUG-repeat foci), not the DMPK protein. A protein degrader would not address the RNA-level toxicity. The correct route is antisense oligonucleotides that degrade the toxic RNA, or splice-modulating small molecules.
05Treatment today
06In the pipeline
- Antisense oligonucleotides targeting the CUG-repeat RNA (e.g. baliforsen/IONIS-DMPKRx — clinical)
- Small-molecule MBNL1 splice modulators (preclinical)
- CRISPR/Cas9 excision of the CTG repeat (preclinical)
Key reference: PMID 40983775 · PubMed
07Verification
Every line below is the registry's own verification record — what was checked, against which source, and what is still open.
- uniprot: Q09013 = DMPK (Myotonin-protein kinase), 629 aa — VERIFIED via UniProt REST API (live)
- gene mutation: CTG repeat expansion in DMPK 3' UTR — VERIFIED (OMIM 160900)
- inheritance: Autosomal dominant — VERIFIED (OMIM 160900; Orphanet)
- orpha code: 273 = Steinert myotonic dystrophy (Active) — VERIFIED via Orphanet API (live, 2026-07-02)
- drug mw: No approved disease-modifying therapy — N/A
- fda date: No FDA-approved disease-modifying therapy — N/A
08Sources
| Fact | Source | Accession | Retrieved |
|---|---|---|---|
| Gene/protein identity | UniProt | Q09013 (DMPK, 629 aa) | 2026-10-04 |
| Disease classification & definition | Orphanet | ORPHAcode 273 (Steinert myotonic dystrophy) | 2026-10-04 |
| Inheritance & genetics | OMIM | 160900 (Myotonic Dystrophy 1) | 2026-10-04 |
Corrections carried into registry v2 (2)
- VERIFIED (2026-10-04): built fresh. ORPHAcode 273 confirmed live via Orphanet API.
- CLARIFIED: DM1 is RNA-TOXICITY (mutant CUG-repeat mRNA sequesters splicing factors), NOT protein toxicity. The correct modality is antisense RNA degradation, not a protein degrader.