Pexelizumab: a novel therapy for myocardial ischemia-reperfusion.
Despite significant advances in the study of myocardial reperfusion, patients with epicardial coronary reperfusion still have adverse clinical outcomes. This is in part due to an inflammatory reaction in the injured tissue. Inflamed myocardial tissue after ischemia and reperfusion releases several cytokines and toxic metabolites that lead to reperfusion injury and cellular apoptosis. Complement activation appears to mediate myocardial damage through both these pathways. Recently, pexelizumab, a novel C5 complement monoclonal antibody fragment, has been developed to prevent the complement-mediated myocardial damage from myocardial ischemia and reperfusion. In animal studies, pexelizumab decreased the amount of myocardial damage with ischemia and reperfusion. Pexelizumab has been studied in phase II and phase III clinical trials involving patients undergoing coronary artery bypass grafting and in patients with acute myocardial infarction as an adjunct to reperfusion therapy. Two large clinical trials are currently underway in coronary artery bypass surgery and acute myocardial infarction patients undergoing primary percutaneous revascularization. This review will cover the pathophysiological role of complement activation with regards to ischemia-reperfusion injury, the novel compound pexelizumab, and both the preclinical and clinical data for pexelizumab use in coronary artery bypass surgery and acute myocardial infarction patients.
Patel
Manesh R
MR
Division of Cardiology, Duke Clinical Research Institute, Duke University Medical Center, Durham, North Carolina, USA. patel017@dcri.duke.edu
Granger
Christopher B
CB
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D002986:Clinical Trials as Topic; D006801:Humans; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy*; D057127:Single-Chain Antibodies; D013678:Technology, Pharmaceutical / Q000379:methods / Q000639:trends
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D057127:Single-Chain Antibodies; C402724:pexelizumab