Identification of enzymatically modified isoquercitrin as a therapeutic lead for myotonic dystrophy type 1.

ABSTRACT: Myotonic dystrophy type 1 (DM1) is a complex multisystemic disease caused by a CTG repeat expansion in the DMPK gene for which there are no approved disease-modifying treatments. Transcription of the expanded allele produces toxic gain-of-function CUG-expansion RNA that sequesters the MBNL family of alternative splicing regulators into ribonuclear foci, leading to pathogenic mis-splicing. In this study, using our previously established HeLa DM1 repeat selective screening platform, we identified the natural flavonoid quercetin as a selective modulator of toxic CUG RNA levels. Quercetin treatment selectively reduced DMPK levels and rescued MBNL-dependent mis-splicing in DM1 patient-derived myotubes. To overcome the limited bioavailability of quercetin in vivo, we evaluat

SUBMITTER: Mishra SK 

PROVIDER: S-EPMC12910114 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature