Small molecule inhibitors of phagocytosis as replacement therapy for IVIG

Therapies using antibody preparations can be successful to alleviate, or even cure a number of disorders and have become a common treatment for a variety of blood diseases where blood cells are eliminated, including immune cell-mediated ITP. ITP is an autoimmune disease characterized by rapid clearance of blood cells by phagocytic cells in the spleen and liver. Antibody therapies to treat ITP and other autoimmune disorders are becoming more and more prevalent. In addition to significant cost, particularly for the antibody therapy IVIG, where gram quantities are required for success, there are reports of mild to severe side effects including, in rare instances, death. More recently, IVIG-associated side effects have become increasingly prevalent and US Food and Drug Administration issued a warning for use of IVIG. There are also worldwide shortages due to these products having a human source requirement. Also, because of the requirement for human donors to produce the product, a rare but not trivial potential for disease transmission exists. Canada is the largest user of IVIG antibodies per capita in the world and IVIG is provided solely by the Canadian Blood Services. Indeed, the cost to the Canadian Blood Services of providing IVIG to Canadians is estimated to amount to approximately 25% of their total operating budget. Hence, the development of novel, nonhuman-derived, and less expensive therapies to replace or enhance existing immunoglobulin therapies would prove to be beneficial, both to patients and the Canadian blood program. We propose to develop small molecule drugs to replace IVIG therapies for the treatment of ITP-like blood disorders using proven drug design methods. This new class of drugs would be useful in therapies involving patients having ITP and other immune-mediated blood cell disorders in children as well as adults, and would have the potential to replace a significant portion of the worldwide use of IVIG.

BRANCH, Donald

St. Michael's Hospital

Canadian Blood Services-CIHR Partnership Operating Grant Program

Ontario

$230,000