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Publication of the Month |August 2020

    Home Publication of the Month Publication of the Month |August 2020

    Publication of the Month |August 2020

    By The McGowan Institute For Regenerative Medicine | Publication of the Month, Publication of the Month 2020 | 0 comment | 27 August, 2020 | 0

    Author: Jonas Wilbs, Xu-Dong Kong, Simon J Middendorp, Raja Prince, Alida Cooke, Caitlin T Demarest, Mai M Abdelhafez, Kalliope Roberts, Nao Umei, Patrick Gonschorek, Christina Lamers, Kaycie Deyle, Robert Rieben, Keith E Cook, Anne Angelillo-Scherrer, Christian Heinis

    Title: Cyclic peptide FXII inhibitor provides safe anticoagulation in a thrombosis model and in artificial lungs

    Summary: Inhibiting thrombosis without generating bleeding risks is a major challenge in medicine. A promising solution may be the inhibition of coagulation factor XII (FXII), because its knock-out or inhibition in animals reduced thrombosis without causing abnormal bleeding. Herein, we have engineered a macrocyclic peptide inhibitor of activated FXII (FXIIa) with sub-nanomolar activity (Ki = 370 ± 40 pM) and a high stability (t1/2 > 5 days in plasma), allowing for the preclinical evaluation of a first synthetic FXIIa inhibitor. This 1899 Da molecule, termed FXII900, efficiently blocks FXIIa in mice, rabbits, and pigs. We found that it reduces ferric-chloride-induced experimental thrombosis in mice and suppresses blood coagulation in an extracorporeal membrane oxygenation (ECMO) setting in rabbits, all without increasing the bleeding risk. This shows that FXIIa activity is controllable in vivo with a synthetic inhibitor, and that the inhibitor FXII900 is a promising candidate for safe thromboprotection in acute medical conditions.

    Source: Nat Commun. 2020 Aug 4;11(1):3890.

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      • Contact Us
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    • Our Research
      • Focus Areas
        • Tissue Engineering and Biomaterials
        • Cellular Therapies
        • Medical Devices and Artificial Organs
        • Clinical Translation
      • Matrix
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      • Clinical Trials
      • Initiatives
    • Media
      • Current News
      • News Archive
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      • Podcasts
      • Newsletter
      • Grant of the Month
      • Publication of the Month
      • Media Contact
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      • Special Events
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      • CATER
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