Hepcidin as a therapeutic target in iron overload.

Introduction: Dysregulation of the hepcidin-ferroportin axis is a hallmark in the pathogenesis of iron overload, ultimately leading to end-organ injury. Hereditary hemochromatosis and iron-loading anemias are characterized by a hepcidin deficiency, making hepcidin a novel therapeutic target for preventing and managing iron overload.

Areas covered: Modulators of hepcidin expression and molecules mimicking hepcidin are emerging as highly promising therapeutic strategies. We present a summary of results from preclinical and clinical trials of such therapies in models of iron overload.

Expert opinion: Current treatment alternatives in iron overload fail to address the underlying hepcidin deficiency - and may even exacerbate it. Until hepcidin-targeting therapies become available, several challenges remain, including the need to optimize dosing in order to manage the narrow treatment window and improving specificity in targeting iron metabolism pathways exclusively. Long-term studies are crucial to fully assess both the benefits and risks of these therapies and to explore their potential utility in combination with existing treatment guidelines. Furthermore, these therapies are expected to have applications, particularly in addressing other iron-maldistributed disorders, as seen in anemia of chronic disease and inflammation.