An experimental drug developed at Michigan Medicine has shown the ability to reverse severe fatty liver disease in animal studies. The compound, DT-109, works by restoring gut health and interrupting a harmful biological process.

An experimental drug, DT-109, developed at Michigan Medicine, has demonstrated the ability to reverse severe fatty liver disease in animal studies. The findings, published in The Journal of Clinical Investigation, suggest a new approach for treating metabolic dysfunction-associated steatohepatitis (MASH) by targeting the gut-liver connection. MASH is a serious form of fatty liver disease affecting about 7% of people globally, with limited effective treatment options.

Drug Mechanism and Animal Study Results

The investigational compound, DT-109, is a glycine-based tripeptide. Researchers found it reversed MASH in animal models by interrupting a harmful biological process linking the gut and liver. The team identified an overgrowth of the bacterium Clostridium perfringens, which generates ammonia, as a major contributor to the disease. High ammonia levels damage the intestinal barrier, allowing harmful microbial products to enter the bloodstream, reach the liver, and trigger inflammatory responses. DT-109 reduced Clostridium perfringens levels and lowered ammonia production in the intestines of both mice and nonhuman primates. This strengthened the intestinal barrier, limiting the movement of harmful substances from the gut into the body. In nonhuman primates, whose biology closely resembles humans, DT-109 reduced liver inflammation and significantly improved MASH severity.

Potential Broader Applications

Researchers believe DT-109 may have uses beyond treating fatty liver disease. Previous studies from Eugene Chen's laboratory showed the compound could reduce atherosclerosis plaques and prevent vascular calcification in nonhuman primates, suggesting its potential as a treatment for cardiovascular disease. Additionally, because intestinal barrier breakdown is linked to several digestive disorders, the team believes DT-109 could be explored for conditions like inflammatory bowel disease (IBD). Future research will focus on further testing to move DT-109 into clinical trials to evaluate its safety and effectiveness in people.