Imagine a groundbreaking drug that could not only halt but also reverse the damage caused by metabolic liver disease and fibrosis. This is the exciting prospect revealed by researchers at McMaster University, who are conducting preclinical studies on a novel drug candidate developed by Espervita Therapeutics. This promising treatment could potentially prevent liver fibrosis—a serious condition characterized by the accumulation of scar tissue in the liver that often leads to cancer.
Recent findings, published in the esteemed journal Cell Metabolism, highlight a significant step towards addressing the urgent need for effective treatments for the millions suffering from liver disease, particularly in Canada where no approved medications currently exist for this condition.
So, what exactly is liver fibrosis? It typically arises as a severe manifestation of a disease known as metabolic dysfunction-associated steatohepatitis (MASH), which frequently affects individuals with obesity or metabolic disorders like type 2 diabetes. Beyond its links to cancer, liver fibrosis can also increase the risk of heart attacks and strokes, and in the most severe cases, may necessitate a liver transplant. Alarmingly, despite the seriousness of these outcomes, options for treating MASH and related liver conditions remain frustratingly limited.
Greg Steinberg, a professor in the Department of Medicine at McMaster and the lead author of this research, states, "Currently, we have no drugs approved in Canada to treat MASH. Patients are mainly advised to follow a Mediterranean diet along with some lifestyle changes, but there are no specific medical treatments available here."
He adds that while two therapies have recently gained approval in the United States and Europe, they have shown efficacy in reducing fibrosis in only about one-third of patients.
While existing treatments may slow the progression of liver disease, they generally fail to reverse the fibrosis-related damage that has already occurred. However, early preclinical data suggests that the new drug candidate being studied in Steinberg's lab—developed in collaboration with Espervita Therapeutics—could change that narrative.
The research team, which includes experts from the United States, France, and Australia, has demonstrated the powerful healing properties of this novel small-molecule therapy in various disease models. The drug, EVT0185, has been associated with several beneficial effects, including better blood sugar control, reduced cholesterol levels, and the elimination of fat buildup that contributes to liver fibrosis.
Originally identified as a potential treatment for liver cancer due to its impressive anti-tumor activity published in Nature, EVT0185 is now being recognized for its potential role in treating MASH as well. Steinberg notes, "There is a pressing need for agents that can reduce liver fibrosis while simultaneously improving blood glucose and cholesterol levels. This drug addresses a significant therapeutic gap and could fundamentally reshape our approach to treating severe liver disease, ultimately preventing complications such as liver cancer, diabetes, and heart disease."
This innovative compound works by targeting two critical enzymes involved in fat synthesis and burning, ACLY and ACSS2. Steinberg describes its action as creating a "carbon release valve" in the body, effectively preventing harmful substances from accumulating in the liver and bloodstream, directing them to be eliminated through urine instead.
Looking ahead, this promising small molecule is set to enter clinical trials by 2027, contingent on completing additional preclinical studies and toxicology assessments. The research received support from multiple institutions, including Espervita Therapeutics, the Canadian Institutes of Health Research, MITACS, and McMaster University.
