Chitinase-1 Inhibition Attenuates MASH Progression: A Novel Therapeutic Approach via Metabolic Reprogramming
In May 2025, a collaborative research team from OncoArendi Therapeutics and academic institutions in Poland published a study in Frontiers in Immunology highlighting the therapeutic potential of the CHIT1 inhibitor OATD-01. Using multiple MASH (metabolic dysfunction-associated steatohepatitis) models, including the STAM™ mouse, the study demonstrated that OATD-01 can modulate macrophage metabolism and suppress disease progression.
In this study, MASH model mice were treated with OATD-01 for four weeks. The treatment led to significant reductions in hepatic steatosis, inflammation, and fibrosis. Histological assessments showed improved NAS (NAFLD Activity Score), and immunohistochemical analysis revealed decreased expression of inflammatory macrophage markers such as CD68 and F4/80. Furthermore, RNA-Seq analysis showed that OATD-01 normalized the expression of a wide range of genes involved in lipid metabolism, glycolysis, and mitochondrial function.
In vitro experiments using bone marrow-derived macrophages (BMDMs) revealed that OATD-01 treatment reduced glucose uptake and increased ATP production. This metabolic switch was associated with decreased secretion of pro-inflammatory cytokine IL-1β, suggesting a novel anti-inflammatory mechanism through CHIT1 inhibition and macrophage metabolic reprogramming.
This study provides compelling evidence that targeting CHIT1 can restore liver homeostasis and prevent disease progression in MASH. With OATD-01 currently undergoing Phase II clinical trials, its application in metabolic liver diseases holds promise. SMC Laboratories remains committed to supporting innovative research and providing high-quality preclinical study services to accelerate drug development.