Breakthrough new drug effectively treats the world’s most common liver disease

A study led by the University of Barcelona proposes that the drug pemafibrate could be an effective treatment for liver disease linked to metabolic disorders. This condition, the most prevalent liver pathology globally, impacts one in four people. Pemafibrate, currently used in Japan to improve blood lipid levels in patients with hyperlipidemia, could now address this serious liver disease, which still lacks a specific treatment.

The research, conducted on laboratory animals, was published in the journal Biomedicine & Pharmacotherapy. The team was led by Professor Juan Carlos Laguna from the UB’s Faculty of Pharmacy and Food Sciences, IBUB, and CIBEROBN. Collaborating with them was Professor Conxita Amat’s group from the Department of Biochemistry and Physiology and INSA-UB at the Torribera Food Campus.

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease, is a multisystem disorder. It has a varied origin and can progress to cirrhosis, liver cancer, or liver failure, often without clear symptoms, and can last for decades in its early stages.

Currently, pemafibrate treats dyslipidemia, which involves alterations in blood cholesterol and triglyceride levels. The new research indicates it might also offer a therapeutic solution for MASLD through drug repositioning, a strategy that uses known and approved drugs for new medical conditions. This approach can maximize the therapeutic potential of drugs and reduce the time and cost of developing new treatments for diseases lacking effective therapies.

“The common pathological manifestation of MASLD is hepatic steatosis (fatty liver disease, or SLD). While lifestyle changes like diet and exercise can reverse it, controlling these changes is challenging, and there are no specific drugs for treatment. Repositioning drugs with a good safety profile is an optimal approach to discovering new treatments,” says Professor Juan Carlos Laguna.

In an experimental model of SLD in female rats, pemafibrate prevents the development of hepatic steatosis, increases fatty acid catabolism, and enhances cholesterol clearance in the liver, all while showing a good safety profile. This preclinical study could also help identify sex differences in chronic disease physiology, reducing gender bias in biomedical research.

“Pemafibrate is a new modulator of the transcriptional activity of the nuclear receptor PPAR-α. It increases hepatic oxidation of fatty acids, essential for synthesizing triglycerides and cholesterol esters, which accumulate pathologically in the liver in SLD. It also aids in the production of bile acids, facilitating cholesterol elimination from the body,” Laguna explains.

These findings suggest that pemafibrate is a strong candidate for therapeutic repositioning to treat SLD. Laguna notes, “To our knowledge, this drug has not been used in the context of pharmacological repositioning, apart from a few exploratory clinical studies on its effects in liver pathology. Now we aim to study its efficacy and safety in experimental models of more advanced liver disease, with the presence of inflammation and fibrosis in metabolic associated steatohepatitis (MASH).”

By repurposing pemafibrate, there is hope for a new and effective treatment for liver diseases linked to metabolic disorders, providing a promising outlook for those affected by this widespread condition.

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