Study Shows Compound Significantly Prevents Progression of Diet-Induced Non-Alcoholic Fatty Liver Disease

Rom et al report that the oral administration of the simple tri-peptide, DT-109 (Patent US8664177B2), prevents both development of non-alcoholic fatty liver disease (NAFLD) and late stage fibrosis in a murine model of diet-induced non-alcoholic steatohepatitis (NASH). The study titled, ‘Glycine-based treatment ameliorates NAFLD by modulating fatty acid oxidation, glutathione synthesis, and the gut microbiome’ was published in Science Translational Medicine on 2 December 2020.

DT-109 is a 3 amino acid, orally active peptide, that stimulates release of intestinal GLP-1. Dr Eugene Chen and his team at the University of Michigan identified DT-109 as having dual glucose/lipid-lowering effects and potently lowering steatohepatitis and fibrosis in a long-term pre-clinical NASH model. Applying advanced multi-omics approaches, the team identified underlying mechanisms by which DT-109 protects against NAFLD. These included modulation of the gut microbiome, stimulation of lipid utilisation in the liver and the production of one of the most protective antioxidants, glutathione.

Dr Oren Rom, the study lead author stated: "We thought outside the box and focused on understudied aspects linking dysregulated amino acid metabolism to NAFLD. Our studies not only provided metabolic explanations for impaired glycine metabolism in NAFLD, but also identified a novel glycine-based treatment."

"This promising study shows that certain glycine-based treatments attenuate experimental NAFLD by stimulating hepatic fatty acid oxidation and glutathione synthesis and therefore warrants clinical evaluation beyond initial animal model and in-vitro data. Further studies would be well justified in clinical trials to continue to deliver on the positive outcomes thus far," said Mathew Diggle FRCPath, PhD DLSH&TM MSc - Consultant Microbiologist, Associate Professor and member of the International Working Group for Diabetic Foot Infection.

DT-109 has been licensed from the University of Michigan by Diapin Therapeutics LLC. Dr Bruce Markhan, CEO of Diapin stated: "DT-109 has been designated as a lead NASH compound and is currently being evaluated in preclinical IND enabling studies and developed in chemical manufacturing control. We see this as a breakthrough molecule for the treatment of NASH and other co-morbidities associated with metabolic syndrome."

More information online