New use for a drug: treating the most common liver disease worldwide

A drug that lowers blood lipids could help treat the world’s most common liver disease.

This has been determined by a study led by the University of Barcelona (UB). The authors of the study propose using the drug known as pemafibrate to treat liver disease associated with metabolic disorders, the most common liver pathology in the world, affecting one in four people. This drug has been marketed for some time in Japan for another use: it improves blood lipid levels in patients with hyperlipidemia, a very common disorder in diabetics. However, it could now help combat this serious liver disease, which to date still has no specific treatment.

The research, carried out using laboratory animal models, was conducted by a team led by Professor Juan Carlos Laguna, from the Faculty of Pharmacy and Food Sciences, the Institute of Biomedicine of the UB (IBUB) and the Biomedical Research Network Centre for the Pathophysiology of Obesity and Nutrition (CIBEROBN), in Spain. The work was carried out in collaboration with the research group of Professor Conxita Amat, from the Department of Biochemistry and Physiology of the same faculty, and the Institute for Research in Nutrition and Food Safety (INSA) of the University of Barcelona, ​​based on the Torribera de la Alimentación Campus. The first author of the study is Roger Bentanachs, from the UB and the IBUB.

Repurposing drugs: a new life for medicines

Metabolic-associated liver disease (MASLD) is a disease previously known as non-alcoholic fatty liver disease. It is a multisystem disorder with a very heterogeneous origin and a diverse course that can lead to cirrhosis, liver cancer or liver failure. It does not usually present clear symptoms and the first stages can last for decades.

Today, pemafibrate is used to treat disorders of cholesterol and triglyceride levels in the blood (dyslipidemia). According to the new study, it could also open a new therapeutic avenue to combat MASLD in the context of drug repurposing, i.e. the use of known and approved drugs in clinical practice to treat other pathologies. This strategy makes it possible to fully exploit the therapeutic potential of drugs and thus reduce the time and economic costs of bringing another drug to market to treat diseases without effective therapy.

Finding a new use for drugs already approved by health authorities and used against a disease against another disease is a fast and effective way of finding new treatments for an illness. (Photo: Amazings / NCYT)

“The common pathological manifestation of MASLD is fatty liver disease (SLD). Although it can be reversed with lifestyle changes, diet and exercise, in practice it is difficult to control and there are no specific drugs to treat it,” explains Professor Juan Carlos Laguna.

In an experimental model of SLD in female rats, pemafibrate prevents the onset of hepatic steatosis, increases fatty acid catabolism and cholesterol elimination in the liver, and shows a good safety profile. Since the preclinical study was carried out with female specimens, the conclusions of the work could also help to identify differences in the physiology of chronic diseases based on sex and, thus, reduce gender bias in biomedical research.

«Pemafibrate is a new modulator of the transcriptional activity of the nuclear receptor PPAR-alpha (peroxisomal proliferator-activated receptor alpha), which increases the hepatic oxidation of fatty acids, which are necessary for the synthesis of triglycerides and cholesterol esters —which accumulate pathologically in the liver in LDS— and also for the synthesis of bile acids, which promotes the elimination of cholesterol from the body,» explains the researcher.

These results suggest that pemafibrate is a good candidate for therapeutic repurposing to treat LDS. “As far as we know, this drug has not been used in the context of pharmacological repurposing, apart from some exploratory clinical studies on its effects on liver pathologies. Now, what we want is 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),” concludes Laguna.

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The study is titled “Pemafibrate abrogates SLD in a rat experimental dietary model, inducing a shift in fecal bile acids and microbiota composition.” It has been published in the academic journal Biomedicine & Pharmacotherapy. (Source: University of Barcelona)