Although alcohol is a well-known contributor to liver disease, it is not the only factor that can affect liver health.
High rates of obesity and Type 2 diabetes are closely linked to a severe form of fatty liver disease called MASH, or metabolically dysfunction-associated steatohepatitis. The condition can cause scarring of the liver, cirrhosis and significantly increase a person's risk of developing liver cancer.
"MASH is increasingly prevalent, and when you look at the causes of liver cancer in the U.S., it is now equal to alcohol," said Christian Bréchot, MD, PhD, professor in the Morsani College of Medicine, senior associate dean for research in global affairs and associate vice president for international partnerships and innovation. "This is a huge concern in the U.S. because cases have increased significantly due to poor diet, weight increases and the rise of Type 2 diabetes."
Researchers at the University of South Florida were awarded a new $1.8 million grant from the Florida Cancer Innovation Fund to support a 12-month preclinical study focused on ALF5755, a leading drug candidate being developed to prevent MASH progression and reduce liver cancer risk.
Christian Bréchot, MD, PhD, professor in the Morsani College of Medicine, senior associate dean for research in global affairs and associate vice president for international partnerships and innovation. (Photo by Frederick Coleman)
The project, led by Bréchot in collaboration with the Health Aging Company, will evaluate the efficacy of ALF5755 in targeting several key drivers of MASH, including inflammation, insulin resistance and changes in the gut microbiome.
"This molecule has a combination of unique properties that could be particularly valuable in treating MASH and preventing liver cancer," Bréchot said. "It counteracts inflammation, stimulates tissue regeneration, restores insulin sensitivity, counteracts liver cancer progression and even helps restore a healthy gut microbiome."
The study will also examine how ALF5755 works in combination with GLP-1 drugs, which are growing more prevalent in treating diabetes and obesity. While GLP-1 drugs are effective for weight loss and metabolic health, they do not directly act on liver cancer or its key drivers, such as inflammation and microbiome dysfunction.
Rather than replacing those therapies, researchers see an opportunity to enhance them.
"GLP-1 receptor agonists are very effective for weight loss and diabetes, but they don't really address inflammation or liver cell regeneration," Bréchot said. "We do not see this as a replacement. But in combination, it could be much more efficient."
The effort builds on USF's sustained commitment to biomedical research and innovation, particularly through partnerships bridging academia and industry. The Healthy Aging Company, a biotech pharmaceutical research company co-founded and chaired by Bréchot, is based in the USF Research Park and collaborates closely with university scientists.
During the preclinical study, researchers will evaluate both the drug's effectiveness and potential delivery methods, including long-acting approaches that could reduce treatment frequency. If successful, the work would pave the way for future clinical trials for patients living with MASH.
"Liver disease is underappreciated because people do not have symptoms for many years," Bréchot said. "This is really a new avenue for USF and for Florida in addressing liver disease, an area with a significant unmet medical need."
