Grant: Operating Grant

Iron overload disease is primarily caused by the repeated transfusion of red blood cells as implicated in the case of thalassemia, sickle cell anaemia and myelodysplastic syndromes or by the enhanced uptake of dietary iron. These conditions affect millions of people worldwide. Since humans do not have an iron excretion mechanism, excess iron will get deposited in the human body. Free iron is highly toxic to critical organs and tissues. Organ injury is the most important reason for the premature death among iron overloaded patients. To date, the only treatment option available is the life-long iron chelation therapy by administering small iron specific organic molecules which aid in excreting iron either through the kidney or feces. Toxicity, adverse side effects, poor patient compliance and high cost, limit the current treatment with small molecular weight organic molecules. In this project, we propose macromolecular engineering of low molecular weight chelators in the development of novel biodegradable polymer constructs which are non-toxic, long circulating and can remove iron specifically from vasculature or from organs that are mostly affected by iron burden. We anticipate that this novel approach will increase vascular residence time of iron chelators and increase the efficiency of chelation. Macromolecular chelators will provide high patient compliance and improved quality of life to patients by decreasing the adverse side effects.. This would benefit numerous patients worldwide, especially sickle cell and thalassemic patients, suffering from iron overload diseases undergoing iron chelation therapy. The availability of biodegradable non-toxic polymeric chelators will also provide novel methods to treat infection, neurodegenerative diseases and cancer.