Researchers from the UAB and Parc Taulí cure the liver disease MASH, linked to obesity and diabetes, with a single administration of gene therapy

• The treatment, successfully tested in mice, will be the basis of a future clinical trial by the biopharmaceutical company Kriya Therapeutics, Inc. ("Kriya")

Researchers from the UAB and Parc Taulí have succeeded in reversing a liver disease linked to obesity and diabetes that affects more than 40 million people, steatohepatitis associated with metabolic dysfunction (MASH), in model mice. The results have been obtained with a single intramuscular administration of the therapeutic viral vectors. Research has also determined that most people who are obese, have type 2 diabetes and have MASH could benefit from the therapy. The results will form the basis of a future clinical trial by the biopharmaceutical company Kriya. 

A team of researchers from the Autonomous University of Barcelona (UAB) in collaboration with professionals from the Parc Taulí Research and Innovation Institute in Sabadell has described theefficacy and long-term safety in mice of intramuscular administration of a gene therapy for the treatment of MASH, a liver disease that affects approx 40 million people in the United States and Europe.

The therapy developed by the research team is based on genetically manipulating the skeletal muscle with the gene that encodes the protein fibroblast growth factor 21 using adeno-associated viral vectors (AAV-FGF21 vectors). FGF21 is a key metabolic regulator that, after administration of the vectors into skeletal muscle, is increased in the blood circulation in a sustained manner over time (more than a year in this study). This treatment in mice model of the disease it completely and long-term reverses liver fibrosis and MASH, counteracts obesity, excess fat, insulin resistance of type 2 diabetes and the development of liver tumors, both in females and males.

In order to facilitate the step towards the application in people, researchers have evaluated this therapy in dogs to study the safety and therapeutic effect in large animals. They have also characterized the circulating levels of FGF21 in more than 500 obese patients, with type 2 diabetes and MASH, and conclude that most of these patients could benefit from this gene therapy in the future.

The results will be the basis for a future clinical trial, since the UAB licensed this gene therapy program with AAV-FGF21 to the company Tramontane Therapeutics Inc., now part of the Kriya biopharmaceutical company, which will bring this approach to the clinic in human MASH patients. "Our gene therapy based on AAV-FGF21 can be transformative for patients with MASH, a disease that requires safe, effective and long-lasting treatments", explains UAB researcher Fàtima Bosch, who has led the research.

Obesity and type 2 diabetes, precursors of MASH

The global epidemics of obesity and type 2 diabetes are risk factors for the development of liver disease. Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD), or “fatty liver disease", is the most common chronic liver disease worldwide, an epidemic with a prevalence that can reach the 27% of the adult population in some countries. It begins with an excessive accumulation of lipids in the liver that can worsen into severe metabolic dysfunction-associated steatohepatitis (MASH), characterized by inflammation, liver cell (hepatocyte) injury, and fibrosis .

In advanced stages, MASH is associated with severe liver disease, including cirrhosis, liver cancer, and end-stage liver disease, with high mortality. For Fátima Bosch, "the gene therapy strategy we have developed could represent a major advance in the treatment not only of patients with MASH, but also of other metabolic diseases and related comorbidities that affect millions of people worldwide" .

La research, led by Fátima Bosch, director of the Center for Animal Biotechnology and Gene Therapy of the UAB (CBATEG), professor of the Department of Biochemistry and Molecular Biology of the UAB and member of the CIBER of Diabetes and Associated Metabolic Diseases (CIBERDEM; ISCIII), has had the participation of Mercedes Vergara and Assumpta Caixàs, researchers from the I3PT and professionals from the Parc Taulí University Hospital. The work is published today in the journal Molecular Therapy, the official journal of the American Society for Genetic and Cellular Therapy (ASGCT).

📰 [News developed by the Communication Unit of the Autonomous University of Barcelona]