Metabolic dysfunction-associated steatohepatitis (MASH) — the advanced form of fatty liver disease — affects millions worldwide with few drug options. Researchers analyzed gene expression data from both mice and humans with MASH and pinpointed a previously overlooked protein called MOXD1 as a key culprit. MOXD1 works by interfering with a fatty acid-burning enzyme (ACOX1), steering it into a cellular compartment called the peroxisome in a way that blocks normal fat breakdown. Using AI-assisted drug screening, the team found a small molecule called rM15 that disrupts this interaction. In animal models of diet-induced MASH, rM15 significantly reduced liver fat buildup and disease progression. The findings nominate the MOXD1-ACOX1 pathway as a promising new drug target for a condition that currently has very limited treatment options.
