Charles O Noble
ZoneOne Pharma, USA
Title: Liposome Encapsulated Deferoxamine is a More Effective Iron Chelator than Desferal® in an Iron Overloaded Mouse Model
Biography
Biography: Charles O Noble
Abstract
Heart failure is the most common cause of death in children and adults with blood transfusion dependent thalassemia or sickle-cell disorders. This is because long-term transfusions cause an accumulation of iron in the body from the broken down heme in hemoglobin. As humans lack a means of eliminating iron, the iron eventually builds to toxic levels in the vital organs, causing generation of reactive oxygen species followed by cellular apoptosis and necrosis. Chelation therapy is prescribed for patients who have excess iron. Marketed chelators have severe drawbacks. Desferal® (deferoxamine, DFO) requires an infusion time of greater than 40 hours per week. Exjade® and Jadenu® both have black box warnings from the FDA related to renal failure, hepatic failure and GI hemorrhage. Patient compliance is the greatest problem with current chelation therapies. We have devised a novel, stable liposome (LDFO) formulation containing a high concentration of the iron chelator deferoxamine. Toxicology studies show that prototype formulations have no adverse effects well above the therapeutic dose for LDFO indicating that it is better tolerated than Desferal®. Our results show that LDFO efficiently removes iron from the liver and spleens of iron overloaded mice. A single treatment with LDFO results in greater iron excretion than a 14 day continuous infusion of Desferal®. Successful translation of LDFO to patients would result in improved liver iron removal and less frequent dosing and than current options. This work was supported by NIH SBIR Grant 1R43D075429-01 and 1R43D075429-02.