Hoth, VA partner on head-to-head study in fatty liver disease mice
Treatment with GDNF will be tested against semaglutide
Hoth Therapeutics will support a U.S. Department of Veterans Affairs (VA) study testing treatment with glial cell-derived neurotrophic factor (GDNF) against semaglutide in a mouse model of obesity and fatty liver disease. Semaglutide is sold in the U.S. as Wegovy and others.
Researchers will also test GDNF in a specialized mouse model with human liver cells to provide information on its impact on human liver enzymes and other factors.
Prior studies have suggested GDNF therapy may help normalize metabolism in conditions like fatty liver disease. Metabolism refers to the chemical processes that turn food into energy, which can then be used for cellular processes. Semaglutide, a therapy known to have significant metabolic effects, is currently approved in the U.S. for indications including obesity and type 2 diabetes.
“This landmark agreement allows a real-world, controlled comparison of GDNF’s metabolic effects alongside semaglutide — the current gold standard,” Robb Knie, Hoth’s CEO, said in a company press release.
The Foundation for Atlanta Veterans Education and Research (FAVER) is also a partner on the project, which will be conducted at the Atlanta VA Medical Center.
Semaglutide under review as potential medication for MASH
In fatty liver disease, an abnormal amount of fat accumulates in the liver. Typically, this occurs because of changes in the body’s ability to break down fats, which may be related to genetics, environmental factors, or lifestyle. In severe cases, the disease can progress to liver scarring and failure.
Obesity or being overweight are among risk factors for developing fatty liver disease, and treatment may include lifestyle changes and medications to help protect the liver.
Currently, regulatory agencies in the U.S. and Canada are reviewing semaglutide as a potential medication for metabolic dysfunction-associated steatohepatitis (MASH), a severe form of fatty liver disease associated with metabolic issues like diabetes or obesity. The therapy mimics the effects of GLP-1, a hormone that helps regulate blood sugar, appetite, digestion, and other metabolic processes.
GDNF, a protein involved in the development and survival of some nerve cells, may also be able to enhance metabolic activity and reduce the accumulation of fat in conditions like fatty liver disease. Scientists don’t entirely understand the mechanisms behind its metabolic impacts, but GDNF has shown protective effects on liver cells in various studies.
Study to examine impacts on human liver cells in mouse models
Although these studies have so far been restricted to mice, several clinical trials have tested GDNF-related therapies in people with neurological conditions, with results supporting a favorable safety profile.
Because of preclinical promise and initial evidence of clinical safety, there is interest in developing GDNF-based treatments for metabolic conditions. The partnership between Hoth, the VA, and FAVER aims to advance this research.
Investigators will directly compare GDNF to semaglutide and examine impacts on human liver cells in mouse models.
In the first part of the study, researchers will use mice fed a high-fat, high-sugar diet, which can induce obesity and fatty liver disease. The animals will receive daily injections of either GDNF, semaglutide, or a placebo, and will be monitored for changes in weight, liver cell health, and metabolic markers.
Genetically engineered mice with human liver cells will be the subjects of the second part of the study. In these animals, the team plans to administer GDNF therapy and assess changes in the activity of human liver-specific genes and metabolic processes. This may help the researchers understand how the therapy would work in humans.
Study funding will come from Hoth, which will supply GDNF, while the VA will retain the rights to the study results.
“We are proud to support the VA’s efforts in exploring bold new solutions for obesity and liver disease,” Knie said.
