Repeat length as a key determinant for disease severity and antisense oligonucleotide activity in myotonic dystrophy type 1.

ABSTRACT: Myotonic dystrophy type 1 (DM1) is caused by a (CTG) _n expansion in the DMPK gene, leading to a multisystemic manifestation and broad disease presentation. Although the DM1 phenotype and onset correlate with expansion length, understanding DM1 etiology and developing effective therapies remains challenging. Here, we investigated the contribution of repeat length on aberrant splicing and response to antisense oligonucleotides (ASOs). In primary DM1 myoblasts bearing repeat lengths of 800, 1,200, or >3,000, DMPK downregulation was achieved by blocking and gapmer ASOs, though splicing correction was inefficient. Further analyses revealed profound differences in DMPK mRNA levels. To exclude such confounding effects, we generated an isogenic myoblast panel

SUBMITTER: El Boujnouni N 

PROVIDER: S-EPMC12221585 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature