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Scientific Transfer

USC CiMUS Researchers Reveal New Therapeutic Potential of Resmetirom, the Only Approved Drug for Liver Fibrosis

  • The study, recently published in the prestigious journal MedComm, reveals that the drug also inhibits the activation of hepatic stellate cells, which drive the development of severe complications such as cirrhosis and liver cancer.
  • The discovery opens up new opportunities for the development of therapies specifically targeting liver fibrosis, a condition that affects approximately one quarter of the world's population and represents one of the leading causes of chronic liver disease.

Researchers from the Molecular Metabolism group at the Universidade de Santiago de Compostela (USC), led by Rubén Nogueiras at the Center for Research in Molecular Medicine and Chronic Diseases (CiMUS), have identified new therapeutic properties of Resmetirom, the only drug currently approved for the treatment of liver fibrosis associated with metabolic dysfunction-associated steatotic liver disease (MASLD).

MASLD affects approximately 25–30% of the global population and is one of the leading causes of chronic liver disease. Its most severe form is characterized by liver inflammation and the progressive accumulation of scar tissue (fibrosis), which can irreversibly damage the organ and progress to cirrhosis, liver failure, or liver cancer. In this process, hepatic stellate cells play a central role, as their activation is the main driver of fibrosis formation..

Eva Novoa, CiMUS researcher and first author of the study published in MedComm, explains: "Until now, Resmetirom was believed to exert its main effects in hepatocytes by promoting fat loss. However, our results demonstrate that it also acts directly on hepatic stellate cells, reducing their activation and their fibrogenic capacity.". Alba Cabaleiro, co-first author of the study, adds: "These findings help explain how Resmetirom can simultaneously improve both metabolic alterations and fibrosis in the context of MASLD."

Preventing scar tissue formation and halting the progression to cirrhosis or liver cancer
The researchers also identified the molecular mechanism underlying this effect. The study demonstrates that Resmetirom's antifibrotic activity depends on the activation of the thyroid hormone receptor alpha (THRα), which is predominantly expressed in hepatic stellate cells, as well as on the enzyme fatty acid amide hydrolase (FAAH). When either of these two components was experimentally blocked, the drug lost much of its ability to prevent the activation of the cells responsible for fibrosis.

The findings further reveal that Resmetirom acts through two complementary mechanisms. In hepatocytes, it reduces fat accumulation via the THRβ receptor, while in hepatic stellate cells it directly limits fibrosis through the THRα–FAAH signaling pathway. This discovery provides a clearer explanation for the clinical efficacy observed with Resmetirom and opens new avenues for the development of therapies specifically targeting liver fibrosis.
The study was carried out through extensive national and international collaboration involving researchers from CiMUS at the Universidade de Santiago de Compostela, the Spanish Biomedical Research Networking Center for Physiopathology of Obesity and Nutrition (CIBEROBN), the Biomedical Research Networking Center for Liver and Digestive Diseases (CIBERehd), CIC bioGUNE, IDIBAPS, the University of Lille (France), and the University of Lübeck (Germany).

Article: 
E. Novoa, A. Cabaleiro, B. López-Picallo, et al. “Resmetirom Ameliorates Fibrogenesis in Hepatic Stellate Cells via Thyroid Hormone Receptor Alpha-Fatty-Acid Amide Hydrolase 1 Signaling Pathway.” MedComm 7, no. 8 (2026): e70901. https://doi.org/10.1002/mco2.70901

About CiMUS -USC
The Centre for Research in Molecular Medicine and Chronic Diseases (CiMUS) at the Universidade de Santiago de Compostela is dedicated to cutting-edge research on chronic diseases. Its mission is to generate high-impact knowledge that is closely connected to society and focused on improving patients' lives. Its research is organised into two major programmes: Molecular Mechanisms of Disease and Integrative Translational Research. Together, these programmes bridge fundamental science and clinical translation, with a strong emphasis on technology transfer and therapeutic innovation.

CiMUS is an open and collaborative research centre that fosters partnerships with universities, healthcare institutions, industry, and innovation organisations at the regional, national, and international levels. The centre holds the CIGUS recognition awarded by the Xunta de Galicia (ED431G/2023/02), acknowledging the quality and impact of its research. It is funded by the Regional Ministry of Education, Science, Universities and Vocational Training of the Xunta de Galicia and co-funded by the European Union through the Galicia ERDF 2021–2027 Programme. CiMUS has also recently been accredited as a María de Maeztu Unit of Excellence, a prestigious national distinction awarded by the Spanish Ministry of Science, Innovation and Universities (grant CEX2024-001463-M).