There are approximately 450,000 cardiopulmonary bypass (CPB) procedures performed each year in the U.S. Patients undergoing CPB frequently manifest generalized systemic inflammation and if serious, it will lead to prolonged recovery and occasionally serious multi-organ failure. Accumulating evidence suggests that the inflammatory reactions of CPB are triggered by activation of the alternative complement cascade, resulting in other inflammatory responses involving pro-inflammatory cytokines, leukocytes, platelets, endothelial cells, and among others. We have generated a specific anti-human factor D monoclonal antibody (Mab) that inhibits effectively the alternative complement cascade. In this Phase I study, we propose to use a baboon model of CPB to study (1) the pharmacokinetics and pharmacodynamics of the antibody, and (2) the effects of the antibody in inhibiting inflammatory responses. This Phase I study will provide important information to determine the efficacy of the antibody and to validate the therapeutic approach of targeting factor D for development of inhibitors for this indication. The ultimate goal of the study is to develop the anti-factor D antibody for therapeutic use in patients undergoing CPB.
This proposed animal study will provide important proof-of-concept data to support the clinical development of the anti-factor D monoclonal antibody for prevention of serious inflammatory reaction in patients undergoing cardiopulmonary bypass.
| Miller, Akemi; Lu, Chiajung Karen; Wang, Shigang et al. (2009) Pediatric cardiopulmonary bypass circuits: a review of studies conducted at the Penn State Pediatric Cardiac Research Laboratories. J Extra Corpor Technol 41:P50-8 |
