Mouse Model Finds Iron Restriction, Not Excess, Brings Therapeutic Benefit in MDS

Understanding of iron as a pathologic factor in transfusion-independent myelodysplastic syndromes (MDS) has been increased by a recent preclinical mouse model. An analysis of this model supports the use of pharmacologic iron restriction in this setting and was published in Blood.

Analysts used the model to compare the respective effects of iron overload and iron restriction in MDS. They initiated iron overload using FPNC326S genetic activation, and they applied restriction using vamifeport, an oral inhibitor of the iron exporter ferroportin.

Comparison of the two mechanisms found iron excess brought no significant benefit at late-stage erythropoiesis, while red blood cell maturation improved when iron was restricted. Iron excess was found to worsen myeloid bias, however, it was improved by iron restriction. Iron excess also had negative effects on the hematopoietic stem and progenitor cell pool, while restriction benefited the pool.

The analysts highlighted that the MDS mouse model showed clear anemia and survival benefits from vamifeport iron restriction, along with a delay in leukemic transformation. They noted that “the combined therapy with vamifeport and the erythroid maturation agent luspatercept has superior effect in improving anemia and myeloid bias as compared to single treatments, and offers additive beneficial effects in MDS.”

Reference

Antypiuk A, Vance S, Sharma R, et al. Genetic iron overload aggravates and pharmacological iron restriction improves MDS pathophysiology in a preclinical study. Blood. 2024. doi:10.1182/blood.2024026135