New ways to treat a rare liver disease

The IIS Aragón participates in this study which highlights that Peroxisome proliferator-activated receptors (PPARs) are emerging as a potential therapeutic target for primary biliary cholangitis. a rare autoimmune disease that affects the liver and can progress to cirrhosis.

Peroxisome proliferator-activated receptors (PPARs) are emerging as a potential therapeutic target for primary biliary cholangitis. a rare autoimmune disease that affects the liver and can progress to cirrhosis. A study published in Trends in Molecular Medicine Led by Manuel Vázquez-Carrera, head of the Diabetes and Associated Metabolic Diseases group at CIBER (CIBERDEM) in the Faculty of Pharmacy and Food Sciences and the Institute of Biomedicine (IBUB) of the University of Barcelona and the Sant Joan de Déu Hospital, it brings together the most recent advances on the role of these receptors in the development of the disease and shows how their activation influences processes related to both liver damage and the metabolic alterations characteristic of type 2 diabetes.

La primary biliary cholangitis It occurs when the immune system attacks the small ducts that carry bile within the liver. As a result, bile accumulates, promoting inflammation and progressive damage to the organ. Although there is a first-line treatment, around 40% of patients do not respond adequately or cannot tolerate it, making it necessary to develop new therapeutic alternatives.

"The study analyzes the scientific evidence on PPAR agonists, a family of drugs that work by regulating processes essential for liver function. These include the recently approved elafibranor and seladelpar, which have expanded treatment options for people with primary biliary cholangitis." says Xavier Palomer, first author of the article and researcher in Dr. Vázquez-Carrera's group.

According to the research team, which included, among others, Sandra García-Mateo, researcher in the area of ​​Liver and Digestive Diseases of the CIBER (CIBEREHD) at the Lozano Blesa Clinical Hospital, the IIS Aragón and the University of Zaragoza, and Ricardo Rodríguez-Calvo, CIBERDEM researcher in the Lipid and Arteriosclerosis Research Unit and the Biomedical Research Institute of Catalonia South, Activation of PPAR receptors helps reduce inflammation and promotes bile acid balance. —whose accumulation is toxic to the liver— and could slow the progression of fibrosis, one of the main factors associated with the deterioration of liver function.

Beyond their role in this disease, PPAR receptors participate in biological mechanisms shared with type 2 diabetes. Specifically, they regulate fat metabolism, insulin sensitivity, and the inflammatory response—processes altered in both metabolic diseases and certain liver diseases. Understanding these connections can facilitate the development of treatments targeting common mechanisms and contribute to a more integrated view of both diseases.

The research team also analyzes the available clinical evidence on various PPAR agonists and It concludes that these therapies have become one of the main alternatives for patients who need a second line of treatment. However, the researchers point out that longer follow-up studies are still needed to confirm its impact on disease progression and its long-term benefits. The work was funded by the ISCIII, MICIN, FEDER funds, and CIBER. In addition to researchers from CIBEREHD and CIBERDEM, Walter Wahli, a researcher at the University of Lausanne, also collaborated on the project.

Item reference:
Palomer X, Rodríguez-Calvo R, García-Mateo S, Wahli W, Vázquez-Carrera M. The emerging role of PPARs in primary biliary cholangitis. Trends Mol Med. 2026 Jun 13: S1471-4914(26)00133-4. doi: 10.1016/j.molmed.2026.05.008.

Source: University of Barcelona/ CIBER