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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
The humanized anti-glycoprotein Ib monoclonal antibody h6B4-Fab is a potent and safe antithrombotic in a high shear arterial thrombosis model in baboons
Thrombosis and Haemostasis, Volume 100, No. 4, Year 2008
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Description
The Fab-fragment of 6B4, a murine monoclonal antibody targeting the human platelet glycoprotein (GP) Ibα and blocking the binding of von Willebrand factor (VWF), is a powerful antithrombotic. In baboons, this was without side effects such as bleeding or thrombocytopenia. Recently, we developed a fully recombinant and humanized version of 6B4-Fab-fragment, h6B4-Fab, which maintains its inhibitory capacities in vitro and ex vivo after injection in baboons. We here investigated the antithrombotic properties, the effect on bleeding time and blood loss and initial pharmacokinetics of h6B4-Fab in baboons. The antithrombotic effect of h6B4-Fab on acute platelet-mediated thrombosis was studied in baboons where thrombus formation is induced at an injured and stenosed site of the femoral artery, allowing for cyclic flow reductions (CFRs) which are measured on an extracorporeal femoral arteriovenous shunt. Injection of 0.5 mg/kg h6B4-Fab significantly reduced the CFRs by 80%, whereas two extra injections, resulting in cumulative doses of 1.5 and 2.5 mg/kg, completely inhibited the CFRs. Platelet receptor occupancy, plasma concentrations and effects ex vivo were consistent with what was previously observed. Finally, minimal effects on bleeding time and blood loss, no spontaneous bleeding and no thrombocytopenia were observed. We therefore conclude that h6B4-Fab maintains the antithrombotic capacities of the murine 6B4-Fab, without causing side effects and therefore can be used for further development. © 2008 Schattauer GmbH.
Authors & Co-Authors
Fontayne, Alexandre
Belgium, Leuven
Ku Leuven
Meiring, Muriel S.
South Africa, Bloemfontein
University of the Free State
Lamprecht, Seb
South Africa, Bloemfontein
University of the Free State
Roodt, Jan P.
South Africa, Bloemfontein
University of the Free State
Demarsin, Eddy
Belgium, Leuven
Oxurion nv
Barbeaux, Philippe
Belgium, Leuven
Oxurion nv
Deckmyn, Hans
Belgium, Leuven
Ku Leuven
Statistics
Citations: 63
Authors: 7
Affiliations: 3
Identifiers
Doi:
10.1160/TH08-02-0073
ISSN:
03406245