Journal article
Novel thrombolytic drug based on thrombin cleavable microplasminogen coupled to a single-chain antibody specific for activated GPIIb/IIIa
T Bonnard, Z Tennant, B Niego, R Kanojia, K Alt, S Jagdale, LS Law, S Rigby, RL Medcalf, K Peter, CE Hagemeyer
Journal of the American Heart Association | WILEY | Published : 2017
Open access
Abstract
Background-Thrombolytic therapy for acute thrombosis is limited by life-threatening side effects such as major bleeding and neurotoxicity. New treatment options with enhanced fibrinolytic potential are therefore required. Here, we report the development of a new thrombolytic molecule that exploits key features of thrombosis. We designed a recombinant microplasminogen modified to be activated by the prothrombotic serine-protease thrombin (HtPlg), fused to an activation-specific anti-glycoprotein IIb/IIIa single-chain antibody (SCE5), thereby hijacking the coagulation system to initiate thrombolysis. Methods and Results-The resulting fusion protein named SCE5-HtPlg shows in vitro targeting tow..
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Awarded by State Government of Victoria
Funding Acknowledgements
This work was funded by the National Health and Medical Research Council (NHMRC). Bonnard has received funding from the People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme (FP7/2007-2013) under REA grant agreement No. 608765, Niego is supported by a postdoctoral fellowship from the National Heart Foundation of Australia (award No. 100906). Alt was supported by the German Research Foundation (Al 1521/1-1), Peter is a Principal Research Fellow of the NHMRC, and Hagemeyer is a National Heart Foundation Career Development Fellow. The work was also supported in part by the Victorian Government's Operational Infrastructure Support Program and Victoria's Science Agenda Strategic Project Fund.