DOI: http://dx.doi.org/10.1182/blood-2015-10-676742
Minihepcidin peptides as disease modifiers in mice affected by β-thalassemia and polycythemia vera
Carla Casu1, Paraskevi Rea Oikonomidou1, Huiyong Chen2, Vijay Nandi3, Yelena Ginzburg2, Princy Prasad4, Robert E. Fleming5, Yatrik M. Shah6, Erika V. Valore7, Elizabeta Nemeth7, Tomas Ganz7, Brian MacDonald8, and Stefano Rivella1,*
In β-thalassemia and polycythemia vera (PV), disordered erythropoiesis triggers severe pathophysiological manifestations. β-thalassemia is characterized by ineffective erythropoiesis, reduced production of erythrocytes, anemia and iron overload, and PV by erythrocytosis and thrombosis. Minihepcidins are hepcidin agonists that have been previously shown to prevent iron overload in murine models of hemochromatosis, and at higher doses to induce iron-restricted erythropoiesis. Here we show that in young Hbbth3/+ mice, which serve as a model of untransfused β-thalassemia, minihepcidin ameliorates ineffective erythropoiesis, anemia and iron overload. In older mice with untransfused β-thalassemia, minihepcidin improves erythropoiesis and does not alter the beneficial effect of the iron chelator deferiprone on iron overload. In PV mice that express the orthologous JAK2 mutation causing human PV, administration of minihepcidin significantly reduces splenomegaly and normalizes hematocrit. These studies indicate that drug-like minihepcidins have a potential as future therapeutics for untransfused β-thalassemia and PV.
