Delpacibart Etedesiran Improves the Molecular Pathology of Myotonic Dystrophy Type 1 in the Phase 1/2 MARINA® Study - PubMed
3 hours ago
- #Myotonic Dystrophy Type 1
- #RNA Therapeutics
- #Antibody-Oligonucleotide Conjugate
- Delpacibart etedesiran (del-desiran) is an antibody-oligonucleotide conjugate (AOC™) designed to target DMPK mRNA in Myotonic Dystrophy Type 1 (DM1).
- DM1 is caused by CTG repeat expansions in the DMPK gene, leading to CUG-repeat RNA toxicity and misregulated splicing via Muscleblind-like (MBNL) protein sequestration.
- Del-desiran reduced mutant DMPK mRNA, increased functional MBNL levels, and corrected mis-splicing in a dose-dependent manner in preclinical and clinical studies.
- The Phase 1/2 MARINA® study demonstrated del-desiran's pharmacodynamic activity in DM1 patients, aligning with results from patient-derived myotubes and Cynomolgus monkeys.
- The AOC™ platform shows potential for broader applications in treating neuromuscular diseases.