Replacement of IVIg by small molecule inhibitors of phagocytosis

Intravenous immunoglobulin (IVIg), consists of billions of antibodies derived from thousands of blood donors. It is often used as therapy in patients where blood cells, such as platelets that help clotting, are being destroyed by the patient through a process called phagocytosis, resulting in an immune cytopenia known as immune thrombocytopenia (ITP). IVIg is thought to block phagocytosis in ITP allowing the platelets to survive. However, issues with IVIg like extremely high cost, and reports of significant side effects have become increasingly concerning. For these reasons, the development of novel, nonhuman-derived, less expensive therapies with low toxicity to replace or enhance existing IVIG therapy would prove beneficial. Using proven drug design methods, we propose to develop drugs to replace or enhance IVIG therapies for the treatment of ITP and other immune cytopenias in children and adults. When lead candidate drugs are identified, we will elucidate the mechanism of phagocytosis inhibition as directly binding to the Fc receptor on effector cells and/or affecting signal transduction whereby inhibiting the phagocytosis “eat me” signal.

BRANCH, Donald

University of Toronto

Graduate Fellowship Program

Ontario

112333.0