Abstract

Several novel interventional and pharmacological therapeutic approaches have been examined in recent years for the prevention of ischemia/reperfusion injury in myocardial infarction; however, most approaches have failed to progress to clinical trials, and the underlying pathological mechanisms of ischemia/reperfusion injury remain poorly understood. The fibrin Bbeta chain-derived peptide FX-06, under development by Ikaria Holdings Inc, is a novel candidate in phase II trials for the prevention of ischemia/reperfusion injury. FX-06 competitively binds to vascular endothelial (VE)-cadherin, thereby inhibiting leukocyte transmigration and initiating VE-cadherin-mediated signaling, which tightens the endothelial barrier and reduces capillary leakage. The sequence of FX-06 resembles that of a physiological peptide, and the compound has been well tolerated in clinical trials. In a phase II trial in patients with acute ST-segment elevation myocardial infarction who were undergoing percutaneous coronary intervention, FX-06 significantly reduced the necrotic core zone compared with placebo. Whether FX-06 treatment can have a clinical benefit remains to be established. Nonetheless, the unique mechanism of action and short half-life that distinguish FX-06 from competitive pharmacological agents would allow its use in combination with other drugs, potentially contributing to a successful pharmacological therapy for the prevention of ischemia/reperfusion injury after decades of disappointing results.