Key result
Treatment with APT102 completely prevented thrombotic reocclusion and decreased infarction size by 81% in dogs and 51% in mice without increasing bleeding time, whereas clopidogrel was ineffective.
Why the study?
Does APT102 prevent thrombotic reocclusion and reduce infarct size compared to clopidogrel in animal models of myocardial reperfusion?
Does APT102 prevent thrombotic reocclusion and reduce infarct size compared to clopidogrel in animal models of myocardial reperfusion?
APT102, an engineered human apyrase, effectively prevents thrombotic reocclusion and reduces infarct size without increasing bleeding risk in preclinical models of myocardial reperfusion.
In patients with acute myocardial infarction undergoing reperfusion therapy to restore blood flow through blocked arteries, simultaneous inhibition of platelet P2Y12 receptors with the current standard of care neither completely prevents recurrent thrombosis nor provides satisfactory protection against reperfusion injury. Additionally, these antiplatelet drugs increase the risk of bleeding. To devise a different strategy, we engineered and optimized the apyrase activity of human nucleoside triphosphate diphosphohydrolase-3 (CD39L3) to enhance scavenging of extracellular adenosine diphosphate, a predominant ligand of P2Y12 receptors. The resulting recombinant protein, APT102, exhibited greater than four times higher adenosine diphosphatase activity and a 50 times longer plasma half-life than did native apyrase. Treatment with APT102 before coronary fibrinolysis with intravenous recombinant human tissue-type plasminogen activator in conscious dogs completely prevented thrombotic reocclusion and significantly decreased infarction size by 81% without increasing bleeding time. In contrast, clopidogrel did not prevent coronary reocclusion and increased bleeding time. In a murine model of myocardial reperfusion injury caused by transient coronary artery occlusion, APT102 also decreased infarct size by 51%, whereas clopidogrel was not effective. These preclinical data suggest that APT102 should be tested for its ability to safely and effectively maximize the benefits of myocardial reperfusion therapy in patients with arterial thrombosis.
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Moeckel et al. (2014) studied Arterial thrombosis and myocardial reperfusion injury. APT102 vs. Clopidogrel was evaluated on Infarction size and thrombotic reocclusion. Treatment with APT102 completely prevented thrombotic reocclusion and decreased infarction size by 81% in dogs and 51% in mice without increasing bleeding time, whereas clopidogrel was ineffective.
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