Abstract: Provided are methods for increasing hepcidin expression, treating a disorder associated with iron overload, decreasing non-transferrin bound iron (NTBI), reducing spleen size, ameliorating ineffective erythropoiesis, decreasing iron uptake by erythroid cells, and increasing transferrin receptor 1 (TfR1) expression in a subject in need thereof, comprising administering to said subject a therapeutically effective amount of a modified iron binding/releasing transferrin, wherein said modified iron binding/releasing transferrin comprises an N-lobe and a C-lobe, and wherein one of said lobes binds iron, and wherein one of said lobes has a decreased binding affinity for iron.

Abstract: Disclosed herein are methods for treating disease, such as diseases of iron overload, including ?-thalassemia, comprising administering at least one course of transferrin and thereby reducing the size of the spleen in said patient and reducing the concentration of iron in the tissues and blood.