Grant: Operating Grant

Iron overload disease is primarily caused by the enhanced uptake of dietary iron (e.g. hemochromatosis) or by the repeated transfusion of red blood cells (RBCs) such as in the case of thalassemia and sickle cell anaemia disease. In the case of thalassemic patients, ~ 25 to 50 units of RBCs each containing ~250 mg iron are transfused annually to treat anaemia. Since humans do not have an iron excretion mechanism, this huge excess of iron (daily iron uptake is 1-2 mg) will get deposited in the human body. The free iron is highly toxic to critical organs and tissues. Organ failure is the most important reason for the premature death among iron overloaded patients and ~50% patients die by the age of 35 years. The only treatment option currently available is life long iron chelation therapy by administering small iron specific organic molecules which aid in excreting iron either through the kidney or feces. The toxicity, adverse side effects, patient compliance and high cost are the important draw backs of current chelation therapy which use small molecular weight organic chelators. In this proposal, we are developing a novel non-toxic, long circulating and organ specific macromolecular iron chelator which will significantly reduce the toxicity and deplete excess iron from the blood and critical organs in the human body. The new chelating agents will eliminate the adverse side effects caused by the drug and increase the patience compliance by decreasing the number of drug injections needed per week. This will represent the first organ specific macromolecular iron chelator. The development of such a novel macromolecular iron chelator has the potential to help and significantly improve the quality of life of millions of patients suffering from anaemic diseases such as thalassemia and sickle cell anaemia, and hemochromatosis.