The ultimate objective is to develop a compound additive for apheresis products that extends the storage life and function of granulocytes. Granulocytes have a short circulating half-life because they are programmed to die by apoptosis. They also die and lose function when stored ex vivo following apheresis, this has hindered the therapeutic use of granulocyte transfusions. Idun Pharmaceuticals has proprietary small molecules that inhibit apoptosis. These compounds work by inhibiting caspase enzyme(s) that form part of the apoptotic cascade. Neutrophils isolated from normal volunteers are a useful experimental model for studying the effects of these compounds on granulocytes apheresis product stored ex vivo. Preliminary experiments indicate that these compounds can delay morphological aspects of apoptosis in isolated neutrophils for more than 48h. The proposed research is designed to determine if, and for how long, a caspase inhibitor can preserve neutrophil functions (chemotaxis, oxidative burst, phagocytosis, bactericidal killing) and to identify a lead compound to test in apheresis granulocyte concentrates in a Phase II study. The potential application of a molecule that prevents apoptosis of granulocytes is useful in the setting of apheresis storage. Prolonged storage would overcome many of the logistical problems that prevent granulocyte transfusions becoming more widespread. PROPOSED COMMERCIAL APPLICATIONS: A blood product additive that preserves granulocytes ex vivo and extends the shelf life of apheresis products would overcome many of the logistical problems that currently prevents use of granulocyte transfusions from becoming more widespread. The market potential for use in bone marrow or peripheral blood progenitor cells transplant currently is about $10 million. With extension to infectious disease applications the market could triple and developing this class of compounds for in vivo use in oncology would further significantly expand the market.
