The Impact of microRNAs on Dystrophin Rescue and Disease Progression in Duchenne Muscular Dystrophy
Abstract
Previously, we discovered that a small, non-coding RNA, called microRNA 146a (miR-146a), is significantly higher in DMD muscle than in healthy muscle. miR-146a increases as DMD disease worsens and its expression is tightly linked with inflammation. We also found that miR-146a directly blocks dystrophin protein production and its high expression in DMD muscle prevents successful exon skipping dystrophin rescue. Worked proposed in this application test the hypothesis that miR-146a is detrimental to DMD disease course and that blocking miR-146a in combination with exon skipping will improve the amount of rescued dystrophin. We found that inhibiting miR-146ain combination with exon skipping increases dystrophin rescue in the muscle of mdx mice. Further, we found that mdx mice with genetic deletion of miR-146a show significant improvement in muscle function and pathology as compared with mdx mice. This suggest that miR-146a inhibition alone may improve patient outcomes and miR-146a inhibition in combination with exon skipping can improve overall dystrophin rescue.
Document Details
- Document Type
- Technical Report
- Publication Date
- Dec 01, 2019
- Accession Number
- AD1106615
Entities
People
- Alyson A Fiorillo