DT-109, an amino acid compound developed by Michigan Medicine, offers hope for the first-ever human treatment of Nonalcoholic Fatty Liver Disease or NASH.
A new potential drug has shown promise in treating fatty liver disease in animal models, raising hopes for the first human treatment.
Nonalcoholic steatohepatitis (NASH) is a serious liver disease that affects millions of people worldwide. According to a recent study, a recently developed amino acid compound has effectively treated nonalcoholic fatty liver disease in non-human primates, indicating progress towards a treatment for this condition.
With NASH cases rapidly increasing globally, this development brings hope for a future cure for the disease.
DT-109, a glycine-based tripeptide developed by researchers at Michigan Medicine, shows promise in treating Nonalcoholic Steatohepatitis (NASH), a severe form of fatty liver disease that affects up to 6.5% of the global population. NASH causes inflammation and scarring in the liver, leading to potentially life-threatening complications.
The study, conducted in partnership with international teams from the Laboratory Animal Center at Xi’an Jiaotong University Health Science Center and the Institute of Cardiovascular Sciences at Peking University Health Science Center, found that DT-109 successfully reversed fat buildup and prevented scarring in the livers of mice and primates with NASH. These promising results were published in Cell Metabolism.
“For years, scientists have been trying to develop a medication that treats NASH, but many attempts have failed to show an improvement or have raised safety concerns in clinical trials,” adds senior author Eugene Chen. “NASH is rising at a staggering rate, and successful treatment of non-human primates with our drug candidate, DT-109, brings us closer than ever to treating the millions of people suffering from this condition.”
Nonalcoholic Steatohepatitis (NASH) is the second stage of Nonalcoholic Fatty Liver Disease, a condition estimated to affect 32% of the global population. Although exercise and nutritional interventions may help manage fatty liver disease, NASH-related liver damage is more permanent and has become the primary cause of chronic liver disease. In fact, NASH-related cirrhosis is now one of the leading reasons for liver transplantation.
To address this pressing issue, Chen and his team developed DT-109 specifically for treating NASH in non-human primates. This was in response to reports that suggested impaired glycine metabolism as a contributing factor to nonalcoholic fatty liver disease and NASH.
While several compounds, including DT-109, have proven successful in treating NASH in mice, Chen emphasizes that mouse NASH models have limitations. As they do not fully replicate all aspects of the human disease, they are not always easily applicable in clinical settings. To address this, the research team developed a non-human primate model for NASH, confirmed by multiomics profiling studies, which is among the first of its kind.
In both non-human primates and mice, the international research collaboration found that treatment with DT-109 reversed fat buildup and prevented fibrosis progression by enhancing fatty acid degradation and antioxidant formation. Additionally, the drug suppressed the production of lithocholic acid, a harmful secondary bile acid closely linked to nonalcoholic fatty liver disease.
“With this significant breakthrough in preclinical models, we can now consider evaluating DT-109 as a potential drug candidate for the treatment of NASH in future clinical trials,” adds co-corresponding author Jifeng Zhang. “With millions of people suffering from NASH, the need for an effective treatment is more pressing than ever.”
Source: 10.1016/j.cmet.2023.03.013
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