MicroRNAs (miRs) are small non-coding regulatory RNAs. They interact with target messenger RNA transcripts, repress their expression and often induce their destruction. They play an important role in the in normal physiology yet have also been shown to play a role in the pathogenesis of numerous diseases. NAFLD is a complex disease which progresses from simple steatosis (fat accumulation in hepatocytes) to nonalcoholic steato-hepatitis (NASH), which entails extensive inflammation and fibrosis. NASH can progress further to cirrhosis (liver failure) and is a major cause of liver translplantation in Europe and the US. In addition, NAFLD is a major risk factor for hepatocellular carcinoma. In our laboratory we have found a that targeting a specific microRNA can treat a mouse model of NAFLD and restore their liver to normal. We have carried out numerous trials in our mouse model and shown started to identify the dosage, timing and delivery method for longer term treatments. In the course of this grant we have also carried out experiments to better understand the mechanism of action of the treatment as this is an requirement for FDA approval.
