DT-109 Reverses MASH in Animals by Repairing Gut
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- DT-109, a glycine-based tripeptide developed at Michigan Medicine, reversed severe MASH in mice and nonhuman primates by reducing overgrowth of the ammonia-producing bacterium Clostridium perfringens and repairing the gut epithelial barrier, preventing harmful microbial products from reaching the liver.
- MASH affects roughly 7% of people worldwide and can progress to cirrhosis, liver cancer, and liver failure, with limited effective treatment options currently available.
- Lead researcher Eugene Chen, M.D., Ph.D., senior author of the study published in The Journal of Clinical Investigation, said the compound shows clear evidence of protecting the gut barrier and 'has great potential as a treatment for MASH.'
- Nonhuman primate results were especially encouraging because their liver biology and gut microbiota more closely resemble humans, showing reduced liver inflammation and significantly improved MASH severity.
- Earlier studies showed DT-109 can reduce atherosclerosis plaque formation and prevent vascular calcification, and researchers believe it could eventually be explored as a treatment for inflammatory bowel disease and other conditions linked to intestinal barrier breakdown.
- The University of Michigan has patented DT-109 and licensed it to Diapin Therapeutics, which supplied the compound for the study and continues developing it; several researchers including Chen hold ownership interests in the company.
- Co-author Elliot Tapper, M.D., Academic Director of Hepatology at Michigan Medicine, said patients with MASH need 'a safe and effective therapy capable of improving their liver and heart health,' calling the research a promising therapeutic avenue for a condition that remains difficult to treat.
Why it matters: Roughly 7% of the global population lives with MASH, a progressive fatty liver disease that can lead to cirrhosis, liver cancer, and liver failure with limited treatment options — so a compound that works upstream in the gut-liver axis rather than only on the liver itself represents a mechanistic shift. DT-109 has now shown benefits across two animal species including nonhuman primates, bringing it closer to human clinical trials, while the Michigan team's earlier work suggests potential dual liver and cardiovascular benefit.
