The Impact of microRNAs on Dystrophin Rescue and Disease Progression in Duchenne Muscular Dystrophy
Technical Report,01 Sep 2017,31 Aug 2018
Childrens Research Institute Washington United States
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Dystrophin protein is absent in patients with DMD, whereas it is variable in molecular weight and abundance in patients with Becker Muscular Dystrophy BMD. After treating DMD patients with exon skipping drugs to restore dystrophin, the amount of rescued dystrophin in muscle is variable, mirroring what is observed in BMD muscle. To move DMD exon skipping therapies forward, it is imperative that we understand this variability. We recently showed that the pro-inflammatory microRNA, miR-146a, prevents dystrophin production and is much higher in dystrophic versus healthy muscle. In dystrophic mice, we also found miR-146a levels to coincide with worsening of disease state. Treating dystrophic mice with anti-inflammatory drugs that inhibit NF B-driven inflammation reduces miR-146a and improves disease progression. These data suggests a model where the pro-inflammatory state in dystrophic muscle activatesmiR-146a, exacerbating DMD disease and leading to progressive pathology.
- Biomedical Instrumentation and Bioengineering