Extracellular matrix specialist Engitix Ltd. is teaming up with GSK plc to delve into the mechanisms underlying regression of fibrosis after treatment for chronic liver disease, and identify and validate new drug targets involved in this process.

At the recent American Diabetes Association meeting, researchers from Century Therapeutics Inc. presented preclinical efficacy data on CNTY-813, an induced pluripotent stem cell (iPSC)-derived cell therapy engineered using the company’s proprietary Allo-Evasion 5.0 platform.

17-β-Hydroxysteroid dehydrogenase 13 (HSD17B13) and lipid transferase CIDEB are known to contribute to metabolic dysfunction-associated steatohepatitis (MASH) progression, where HSD17B13 exacerbates hepatic lipid metabolism, while CIDEB mainly mediates lipid droplet dynamics and storage. In this context, Frontier Biotechnologies Inc. has presented data on FB-7033, a bispecific siRNA approach targeting both HSD17B13 and CIDEB for the management of MASH.

Transforming growth factor-β-activated kinase 1 (TAK1) is a crucial central signaling molecule of hepatic cell death, inflammation and fibrogenesis through NF-κB and MAPK in metabolic dysfunction-associated steatotic liver disease (MASLD). Its pharmacological inhibition using the TAK1 inhibitor HS-276 was tested in vivo in a murine model of diet-induced MASLD.

There is a growing consensus that alcohol-related liver disease (ALD) should be considered a metabolic disorder under the influence of the gut-liver axis. Metabolome data have highlighted fatty acid-activated G protein-coupled receptors (GPCRs) as the main affected pathways, where the relationship of G-protein-coupled receptor 119 (GPR119) with ALD remains unexplored.

Alterations in PNPLA3, particularly the I148M variant, impair lipid metabolism in hepatocytes, leading to lipid accumulation and driving progression from steatosis to fibrosis and cirrhosis. Targeting this genetic driver may offer a strategy to reduce steatosis and limit disease progression.

Metabolic dysfunction-associated steatohepatitis (MASH) is characterized by lipid accumulation in the liver and inflammation. Sterol O-acyltransferase 2 (SOAT2) is a key enzyme in intestinal absorption and hepatic secretion of cholesterol. PRD Therapeutics Inc. has developed PRD-001, a selective SOAT2 inhibitor currently in phase I trials for MASH.