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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Antithrombotic drug candidate ALX-0081 shows superior preclinical efficacy and safety compared with currently marketed antiplatelet drugs
Blood, Volume 118, No. 3, Year 2011
Notification
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Description
Neutralizing the interaction of the platelet receptor gpIb with VWF is an attractive strategy to treat and prevent thrombotic complications. ALX-0081 is a bivalent Nanobody which specifically targets the gpIb-binding site of VWF and interacts avidly with VWF. Nanobodies are therapeutic proteins derived from naturally occurring heavy-chain - only Abs and combine a small molecular size with a high inherent stability. ALX-0081 exerts potent activity in vitro and in vivo. Perfusion experiments with blood from patients with acute coronary syndrome on standard antithrombotics demonstrated complete inhibition of platelet adhesion after addition of ALX-0081, while in the absence of ALX-0081 residual adhesion was observed. In a baboon efficacy and safety model measuring acute thrombosis and surgical bleeding, ALX-0081 showed a superior therapeutic window compared with marketed antithrombotics. Pharmacokinetic and biodistribution experiments demonstrated target-mediated clearance of ALX-0081, which leads to a self-regulating disposition behavior. In conclusion, these preclinical data demonstrate that ALX-0081 combines a high efficacy with an improved safety profile compared with currently marketed antithrombotics. ALX-0081 has entered clinical development. © 2011 by The American Society of Hematology.
Authors & Co-Authors
Ulrichts, Hans
Belgium, Zwijnaarde
Ablynx nv
Silence, K.
Belgium, Zwijnaarde
Ablynx nv
Schoolmeester, Anne
Belgium, Zwijnaarde
Ablynx nv
de Jaegere, Peter P.T.
Netherlands, Rotterdam
Erasmus Mc
Rossenu, Stefaan
Belgium, Zwijnaarde
Ablynx nv
Roodt, Jan P.
South Africa, Bloemfontein
University of the Free State
Priem, Sofie
Belgium, Zwijnaarde
Ablynx nv
Lauwereys, Marc
Belgium, Zwijnaarde
Ablynx nv
Casteels, Peter
Belgium, Zwijnaarde
Ablynx nv
Van Bockstaele, Femke
Belgium, Zwijnaarde
Ablynx nv
Verschueren, Katrien
Belgium, Zwijnaarde
Ablynx nv
Stanssens, Patrick
Belgium, Zwijnaarde
Ablynx nv
Baumeister, Judith
Belgium, Zwijnaarde
Ablynx nv
Holz, Josefin Beate
Belgium, Zwijnaarde
Ablynx nv
Statistics
Citations: 173
Authors: 14
Affiliations: 3
Identifiers
Doi:
10.1182/blood-2010-11-317859
ISSN:
00064971
Research Areas
Health System And Policy