Minihepcidins improve ineffective erythropoiesis and splenomegaly in a new mouse model of adult beta-thalassemia major.

Minihepcidins are hepcidin agonists that have been previously shown to reverse iron overload and improve erythropoiesis in mice affected by non-transfusion dependent thalassemia. Due to their extreme anemia, the previous model of transfusion dependent thalassemia is inadequate to investigate whether Minihepcidins can improve red blood cell quality, lifespan and, ineffective erythropoiesis. To overcome this limitation, we generated a new murine model of transfusion dependent thalassemia with severe anemia and splenomegaly, but sufficient red cells and hemoglobin production to test the effect of Minihepcidins. Furthermore, this new model demonstrates, for the first time, cardiac iron overload. In absence of transfusion, Minihepcidin improved red blood cell morphology and lifespan as well as ineffective erythropoiesis. Administration of Minihepcidin in combination with chronic red blood cell transfusion further improved the ineffective erythropoiesis and splenomegaly and reversed cardiac iron overload. These studies indicate that drugs like Minihepcidins have therapeutic potential for transfusion dependent thalassemia patients.