{Reference Type}: Journal Article
{Title}: Integrative clinical and preclinical studies identify FerroTerminator1 as a potent therapeutic drug for MASH.
{Author}: Tao L;Yang X;Ge C;Zhang P;He W;Xu X;Li X;Chen W;Yu Y;Zhang H;Chen SD;Pan XY;Su Y;Xu C;Yu Y;Zheng MH;Min J;Wang F;
{Journal}: Cell Metab
{Volume}: 0
{Issue}: 0
{Year}: 2024 Aug 12
{Factor}: 31.373
{DOI}: 10.1016/j.cmet.2024.07.013
{Abstract}: The complex etiological factors associated with metabolic dysfunction-associated fatty liver disease (MAFLD), including perturbed iron homeostasis, and the unclear nature by which they contribute to disease progression have resulted in a limited number of effective therapeutic interventions. Here, we report that patients with metabolic dysfunction-associated steatohepatitis (MASH), a pathological subtype of MAFLD, exhibit excess hepatic iron and that it has a strong positive correlation with disease progression. FerroTerminator1 (FOT1) effectively reverses liver injury across multiple MASH models without notable toxic side effects compared with clinically approved iron chelators. Mechanistically, our multi-omics analyses reveal that FOT1 concurrently inhibits hepatic iron accumulation and c-Myc-Acsl4-triggered ferroptosis in various MASH models. Furthermore, MAFLD cohort studies suggest that serum ferritin levels might serve as a predictive biomarker for FOT1-based therapy in MASH. These findings provide compelling evidence to support FOT1 as a promising novel therapeutic option for all stages of MAFLD and for future clinical trials.