The Antithrombotic Effect of Recombinant Neorudin on Thrombi

INTRODUCTION: Recombinant neorudin (EPR-hirudin, EH) was developed through the addition of an EPR (Glu-Pro-Arg) peptide to the amino terminus of hirudin, which can be recognized and cut by coagulation factors XIa (FXIa) and/or Xa (FXa). In this study, the low-bleeding antithrombotic effects of EH were evaluated utilizing experimental models of thrombosis in rabbits and rats to provide a test basis for clinical trials. METHODS: The bleeding risks of EH and hirudin were first compared in mice by the tail-clipping method, and then the antithrombotic activity of EH was investigated in a rabbit model of arteriovenous bypass thrombosis and a rat model of thrombotic cerebral infarction. RESULTS: In mice, intravenous administration of EH at 1.5 mg/kg and 3 mg/kg did not affect the bleeding time compared with normal saline, while the administration of hirudin at 1.5 mg/kg prolonged the bleeding time by over 3 times the administration of normal saline. Furthermore, intravenous administration of EH had a significant dose-dependent inhibitory effect on the formation and development of arteriovenous bypass thrombosis and thrombotic cerebral infarction. Compared with an equimolar dose of hirudin, the antithrombotic effect of EH was similar, while the bleeding side effects were significantly attenuated. Moreover, when the antithrombotic effects were similar, EH had a shorter bleeding time and was associated with less bleeding than low molecular weight heparin (LMWH). EH had a therapeutic effect on thrombotic cerebral infarction without increasing the occurrence of cerebral hemorrhage. CONCLUSION: The findings from the preclinical animal models used in this study showed that EH could not only effectively inhibit thrombus formation but also reduce the risk of bleeding.

Abstract sourced from PubMed (NCBI) for the cited record. See the original publication for the authoritative version.

EPR-hirudin (neorudin) inhibited arteriovenous bypass thrombosis and cerebral infarction in rabbits and rats without prolonging mouse tail bleeding time at therapeutic doses, even at 3x the classic hirudin dose — demonstrating an engineered safety advantage.

Leech-derived molecules this paper discusses, each with a full profile in the ASH compound registry:

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