NIH R01 · 2025
Small molecule therapeutics for myotonic dystrophy type 1
Summary Myotonic dystrophy 1 (DM1) is an autosomal dominant disorder resulting from the expansion of a CTG repeat tract in the 3’ untranslated region of the DMPK gene. The primary therapeutic target in DM1 is the mutant DMPK RNA encoding expanded CUG repeats (CUGexp), which forms toxic intra-nuclear aggregates or CUGexp foci in patient cells. We have developed an RNA-based screening strategy to identify small molecules that selectively modulate the DMPK CUGexp RNA without affecting the normal DMPK transcript. In a pilot screen of 2,500 compounds we identified a prototype small molecule MDI16, which effectively reverses critical DM1 pathological features in both patient cells and in the…
From the public funding record at NIH RePORTER. Describes the funded project, not the reviews below.