Michigan-based medical researchers have created an innovative peptide therapy for NAFLD that have demonstrated remarkable results. The scientists created DT-109, a glycine-based tripeptide that was evaluated in non-human primates and mice.
The medicine worked well in both instances to reverse fat accumulation and stop liver scarring. The Laboratory Animal Center at Xi’an Jiaotong University Health Science Center and the Institute of Cardiovascular Sciences at Peking University Health Science Center were part of the multinational team that worked on the project. The study was published in Cell Metabolism.
What is NAFLD
Up to 32% of persons globally are afflicted by nonalcoholic fatty liver disease. The hallmark of NAFLD is the buildup of fat in the liver, which can result in inflammation and scarring. The severe variant of NAFLD, nonalcoholic steatohepatitis (NASH), is thought to impact 6.5% of the world’s population and can result in irreversible liver damage. NASH was previously untreatable, but a group of researchers at Michigan Medicine have created a promising new chemical that could change that.
NAFLD and NASH
The prevalence of NAFLD is rising globally at a similar rate to the obesity pandemic. The illness is closely related to the metabolic syndrome, which also includes insulin resistance, hypertension, and obesity. NAFLD can develop into NASH, a more serious type of the condition linked to liver inflammation and scarring.
There are presently no approved therapies for NASH-related cirrhosis, which is one of the most frequent causes of liver transplantation. For those with NAFLD and NASH, lifestyle modifications, including diet and exercise, are advised, but they can be challenging to maintain and do not necessarily undo the damage already done to the liver.
Currently, there are no approved drugs to treat NASH. This is partially a result of the disease’s complexity and the fact that it frequently affects people who already have a number of medical ailments. Additionally, it has been challenging to create and test prospective treatments due to a lack of adequate animal models for NASH.
Study at Michigan Medical School
Based on the researchers’ discovery that NAFLD and NASH are brought on by poor glycine metabolism, the peptide DT-109 was created. Hundreds of drugs have effectively treated NASH in mice, but according to Chen, mouse NASH models are only partially accurate in simulating the human disease and are therefore difficult to translate to the clinic.
One of the first to achieve the feat is the study team’s non-human primate model for NASH, which was validated utilizing multiomics profiling experiments.
Researchers discovered that administering DT-109 to non-human primates and mice reverses fat accumulation and stops the advancement of fibrosis via promoting fatty acid breakdown and antioxidant production.
Lithocholic acid, a hazardous secondary bile acid intimately associated with NAFLD, was also prevented from being produced by the medication.
Researchers and physicians attempting to create efficient treatments for NASH have made considerable strides thanks to the efficacy of the DT-109 peptide in non-human primate models. The substance has demonstrated promising benefits in reversing fat accumulation and avoiding liver scarring, which are two essential characteristics of NASH.
The research team ran a number of tests to see how well DT-109 treated NASH in non-human primate models. After administering the substance to the animals for a number of weeks, the livers were examined for indications of fat accumulation, inflammation, and scarring.
According to the study’s findings, both mice and non-human primates were able to reverse the harm done by NASH when treated with DT-109. The substance inhibited the development of scar tissue, which can result in long-term liver damage, and decreased the accumulation of fat in the liver.
The study team also discovered that DT-109 stimulates the liver’s production of antioxidants and the breakdown of fatty acids. These procedures aid in the breakdown of extra fat that builds up in the liver and assist to avoid the formation of scar tissue.
What lies Ahead
As a result of this important development in preclinical models, Jifeng Zhang, Ph.D., co-corresponding author and research associate professor of cardiovascular medicine at Michigan Medicine, said, “We can now consider evaluating DT-109 as a potential drug candidate for the treatment of NASH in future clinical trials.” The need for an efficient treatment is greater than ever, as NASH affects millions of people.
The usefulness of DT-109 in treating NASH in people will be examined in the near future through clinical trials, according to the researchers. DT-109 might be the first drug for this ailment to be authorized if the studies are successful.