First drug against fatty liver successfully tested in primates

To combat the nonalcoholic fatty liver disease (NAFLD) or hepatic steatosis, the causes and risk factors that lead to its appearance are treated, such as obesity, diabetes or high triglyceride levels, among others, but patients could soon have an effective therapeutic alternative, a drug that is has been successfully tested in non-human primates and that it could become the first treatment of non-alcoholic fatty liver.

NAFLD is characterized by the accumulation of fat in the liver which can be complicated, and even lead to the development of cirrhosis or liver carcinoma, and which is estimated to affect 6.5% of the world population. The new drug is a compound of amino acids –DT-109a glycine-based tripeptide – which has been developed by scientists at Michigan Medicine (USA) to treat the severe form of fatty liver disease: the nonalcoholic steatohepatitis –which is known as NASH–, and which has managed to reverse the accumulation of fat and prevent scarring from forming in the liver of mice and primates with the disease.

The success of the experimental drug DT-109 in non-human primates brings us closer than ever to treating millions of people with non-alcoholic steatohepatitis

“For years, scientists have been trying to develop a drug to treat this serious liver disease, but many attempts have failed to show improvement or have raised safety concerns in clinical trials,” said Dr. Dr. Eugene Chen, lead author of the study. “Non-alcoholic steatohepatitis is increasing at an astonishing rate, and the successful treatment of non-human primates with our drug candidate, DT-109, brings us closer than ever to treating millions of people with this condition.”

A medicine that reverses the symptoms of NAFLD and NASH

Although fatty liver disease can be treated with physical exercise and a proper diet, the damage that NASH causes to the liver is more permanent and has become the main cause of chronic liver diseasewhile NASH-related cirrhosis is already one of the most common reasons for liver transplantation.

Chen and his team developed DT-109 to treat NASH in non-human primates after finding that the poor glycine metabolism it was a cause of nonalcoholic fatty liver disease and NASH. The researchers found that, in both non-human primates and mice, DT-109 treatment reversed fat accumulation and prevented fibrosis progression by stimulating fatty acid breakdown and antioxidant formation. The drug also inhibited the production of lithocholic acid, a toxic secondary bile acid implicated in nonalcoholic fatty liver disease.

“With this important advance in preclinical models, we can now consider the evaluation of DT-109 as potential drug candidate for the treatment of NASH in future clinical trials”, stated Jifeng Zhang, co-author and Research Associate Professor of Cardiovascular Medicine at Michigan Medicine. “With millions of people living with NASH, the need for effective treatment is more pressing than ever.” The results of the study have been published in Cell Metabolism.


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