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 a patient-made autoantibody 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 small molecule, orally-bioavailable drug therapies with low toxicity to replace or enhance existing IVIG therapy would prove beneficial. A therapy to treat or prevent all immune cytopenias where phagocytosis is the known mechanism of cell destruction is most desirable. We have identified several hits from focused libraries that have potential to treat all diseases having phagocytosis as part of the disease process. We propose to further develop these small molecule drugs to replace or enhance IVIG therapies for the treatment of ITP and other immune cytopenias in children and adults. Development of these phagocytosis inhibitors would have the potential to replace a significant portion of the worldwide use of IVIG.

BRANCH, Donald

Canadian Blood Services

Intramural Research Grant Program

Ontario

$399,130