Oral administration of erythromycin decreases RNA toxicity in myotonic dystrophy.

ABSTRACT:

Objective

Myotonic dystrophy type 1 (DM1) is caused by the expansion of a CTG repeat in the 3' untranslated region of DMPK. The transcripts containing an expanded CUG repeat (CUG (exp)) result in a toxic gain-of-function by forming ribonuclear foci that sequester the alternative splicing factor muscleblind-like 1 (MBNL1). Although several small molecules reportedly ameliorate RNA toxicity, none are ready for clinical use because of the lack of safety data. Here, we undertook a drug-repositioning screen to identify a safe and effective small molecule for upcoming clinical trials of DM1.

Methods

We examined the potency of small molecules in inhibiting the interaction between CUG (exp) and MBNL1 by in vitro sequestration and fluorescent titration assays. We studied the effect o

SUBMITTER: Nakamori M 

PROVIDER: S-EPMC4704483 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature