FX-06, a fibrin-derived Bbeta15-42 peptide for the potential treatment of reperfusion injury following myocardial infarction.
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.
Ahrens
Ingo
I
Centre for Thrombosis and Myocardial Infarction, Baker IDI Heart and Diabetes Institute, PO Box 6492, St Kilda Road Central, Melbourne , VIC 8008, Australia. ingo.ahrens@bakeridi.edu.au
Peter
Karlheinz
K
D000595:Amino Acid Sequence; D015906:Angioplasty, Balloon, Coronary / Q000379:methods; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D002986:Clinical Trials as Topic; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D005337:Fibrin / Q000627:therapeutic use*; D005338:Fibrin Fibrinogen Degradation Products / Q000009:adverse effects / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006207:Half-Life; D006801:Humans; D008969:Molecular Sequence Data; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology; D010446:Peptide Fragments / Q000009:adverse effects / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D015427:Reperfusion Injury / Q000188:drug therapy*; D013329:Structure-Activity Relationship; D000099152:Cadherin 5
D015703:Antigens, CD; D015820:Cadherins; D005337:Fibrin; D005338:Fibrin Fibrinogen Degradation Products; D010446:Peptide Fragments; D000099152:Cadherin 5; C033786:fibrinogen Bbeta (15-42)