Common asthma drug formoterol shows potential for MASH

A common asthma drug could offer a new way to treat metabolic dysfunction-associated steatohepatitis (MASH), researchers at the Medical University of South Carolina have discovered. In a paper published in Nature partner journal (npj) Metabolic Health and Disease, they discuss the research that found that formoterol was able to reduce liver fat in mice that had MASH.

MASH is a serious liver disease that causes the liver to swell and can lead to cirrhosis, liver cancer and liver failure. It is linked to Type 2 diabetes and other metabolic conditions such as obesity and affects about 7% of the global population.

Formoterol “reversed the pathology on multiple different levels,” Joshua Lipschutz, M.D., division director of nephrology and the Arthur Williams Endowed Chair in Nephrology at the Medical University of South Carolina, said in a news release. “It looked like formoterol was rescuing the injury by increasing mitochondrial biogenesis. It kind of revs up the mitochondria so they work better.”

Formoterol is a long-acting bronchodilator (LABA) used to treat asthma and manage chronic obstructive pulmonary disease (COPD). Previous research conducted by the investigators had tested formoterol in mouse models of kidney injury to determine if the drug could improve the damage associated with diabetes. This is when they noticed that the mice that received formoterol also appeared to have less liver fat.

That finding led to the current research, in which researchers tested formoterol in mice given a high-fat diet to simulate MASH. In the study, eight-week-old mice were fed a high-fat diet, which led to liver steatosis. After 16 weeks, mice were given daily injections of formoterol for four weeks.

Researchers found that the mice given formoterol had lower body weight compared with those not given formoterol. Steatosis largely resolved in mice treated with formoterol compared with untreated mice. Formoterol mice also had lower scores on the NAFLD Activity Score, which is a tool given to assess severity and changes in fatty liver disease, as well as lower levels of liver lipids.

“We also observed decreases in multiple lipid types in formoterol-treated liver tissue compared to controls, suggesting a net improvement in hepatic lipid accumulation,” researchers wrote.

Researchers did not see a significant change in fibrosis in the mice given a high-fat diet, but they did see repression of fibrosis-relevant genes in the extracellular matrix pathway, an important pathway that supports and regulates key biological processes, including cell differentiation and death.

In addition, researchers conducted a retrospective analysis of patients who were already prescribed beta-2 agonists for respiratory conditions. They assessed a cohort of 59,644 patients with MASH from the TriNetX database. In this real-world analysis, researchers found that the use of formoterol was associated with fewer complications from advanced liver disease and significantly lower rates of several serious liver-related outcomes, including cirrhosis and all-cause mortality.

Researchers also still need to determine what would be an effective dose of formoterol for metabolic disease, whether inhaled delivery will be enough to affect the liver or kidneys in humans and how durable any benefits might be over time.

Lipschutz and his team are currently enrolling patients in a study of formoterol as a possible treatment in both diabetic kidney disease and MASH.