Iron chelation: new therapies

Abstract

Iron chelators are used in clinical practice to protect patients from the complications of iron overload and iron toxicity because there is no physiologic way for excess iron to be actively excreted. Deferoxamine, the only iron-chelating agent available for clinical use in the United States, is administered as a prolonged (8 to 24 hours) infusion, leading to poor compliance in many patients. Although many compounds have been screened in tissue cultures and animals as iron chelators, few have reached the stage of phase I and II clinical trials. The search for new chelating agents, which includes the "slow-release" depot formulation of deferoxamine and the "long-acting" hydroxyethyl starch-deferoxamine, has been disappointing because clinical trials have not demonstrated the intended efficacy. A more promising compound, ICL 670A--an orally active representative of a new class of iron chelators designed by computer modeling-is a potent and selective iron chelator. Its ability to mobilize tissue iron and promote its excretion has been shown in several animal models. In phase I dose-finding trials, ICL 670A was well tolerated and had a good safety profile. This compound is currently undergoing further clinical evaluation.