Iron is essential for different physiological functions and biochemical activities in the body, but is extremely toxic in excess. Because humans don’t have an active mechanism to excrete excess iron, too much iron in the system can lead to iron overload.
The mainstay treatment for many chronic anemia disorders is frequent red blood cell transfusions. Patients with such transfusion-dependent blood disorders are at a heightened risk of iron overload, which can cause severe damage to vital organs including the liver, heart, pancreas, thyroid and endocrine glands. Systemically accumulated iron is fatal if left untreated, and causes considerable morbidity and mortality.
Iron chelation therapy is the most widely-used therapeutic approach to improve survival and reduce the risk of iron overload, by chelating and excreting excess iron using small molecular Fe (III) specific chelators. However, the current FDA-approved iron chelators have many limitations, including inefficiency, toxicity, severe side effects, high cost, and patient non-compliance. Consequently, the lifespan of a major portion of transfusion-dependent anemic patients is severely narrowed. To date, no methods are available for the excretion of organ-deposited iron.
Recent developments in polymer/macromolecular therapeutic approaches shed new light on improving the therapeutic window of small molecular drugs and circumvent the limitations associated with existing therapies. Polymer therapeutics is a widespread multidisciplinary research area with a focus on polymer-conjugates of drugs and proteins, nano drug delivery systems and other macromolecular delivery systems. Several of such systems are approved for market arrival.
Dr. Abbina’s research will investigate improving the success and efficiency of iron chelation by incorporating biodegradable moieties in a polyglycerol scaffold, and targeting specific organs that are susceptible to iron mediated toxicity. The result of this research will be liver- and heart-specific macromolecular iron chelation systems.
The preliminary data is promising and we believe this safe and efficient therapeutic approach would benefit numerous patients suffering from iron overload induced diseases including cardiac failure or arrhythmia, cardiomyopathy, liver diseases and other endocrine disorders. This novel chelating system will also open new avenues to address other iron overload pathogeneses, including cancers, diabetes, inflammation and neurodegenerative diseases.