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Caplacizumab (ALX-0681) is a humanized anti-von Willebrand factor (vWF) nanobody. Caplacizumab inhibits the binding of vWF with platelet glycoprotein (GP) Ibα. Caplacizumab inhibits the vWF-mediated platelet adhesion and prevents further microthrombi formation. Caplacizumab can be used for the research of thrombotic thrombocytopenic purpura (TTP)[1][2][3][4]. | [in vivo]
Caplacizumab (2.5 mg/kg, s.c., daily, from day 1 to day 5 for preventive group) completely prevents the rapid onset of severe thrombocytopenia and schistocytic hemolytic anemia in a baboon model of acquired thrombotic thrombocytopenic purpura, and promotes the recovery of platelet counts after induction of TTP[3].
Caplacizumab (at plasma levels between 0.3-0.5 μg/mL, i.v. bolus) shows a strong antithrombotic effect in a modified Folts model in baboons[4].
Caplacizumab (5 mg/kg total dose with intravenous and subcutaneous injection; intravenous injection first and subcutaneous injections follow) prevents middle cerebral artery thrombosis in a guinea pig model of middle cerebral artery thrombosis, and reduces brain damage without inducing hemorrhage[5].
| Animal Model: | Guinea pig (Dunkin-Hartley, male, 350-400 g) model of middle cerebral artery thrombosis[5] | | Dosage: | 5 mg/kg total dose (0.4 mg/kg intravenously + 1.6 mg/kg subcutaneously at time 0 followed by 3 mg/kg subcutaneously 6 h later) | | Administration: | Intravenous injection first and subcutaneous injections follow | | Result: | Prevented thrombosis when administered immediately after and 15 min after complete occlusion of the middle cerebral artery.
Reduced brain damage area and did not increase intracerebral hemorrhage.
Reduced microvascular thrombosis in the ischemic brain tissue.
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| [References]
[1] Ma?lle le Besnerais, et al. Caplacizumab: a change in the paradigm of thrombotic thrombocytopenic purpura treatment. Expert Opin Biol Ther. 2019 Nov;19(11):1127-1134. DOI:10.1080/14712598.2019.1650908
[2] Nakayama M, et al. Effects of caplacizumab, a specific inhibitor of the A1 domain of von Willebrand factor binding with platelet membrane glycoprotein (GP) Ibα, on the length of platelet pseudopods supporting platelet adhesions on immobilized von Willebrand factor under blood flow condition. Journal of Biorheology, 2022, 36(2): 68-75.
[3] Callewaert F, et al. Evaluation of efficacy and safety of the anti-VWF Nanobody ALX-0681 in a preclinical baboon model of acquired thrombotic thrombocytopenic purpura. Blood. 2012 Oct 25;120(17):3603-10. DOI:10.1182/blood-2012-04-420943
[4] Ulrichts H, et al. Antithrombotic drug candidate ALX-0081 shows superior preclinical efficacy and safety compared with currently marketed antiplatelet drugs. Blood. 2011 Jul 21;118(3):757-65. DOI:10.1182/blood-2010-11-317859
[5] Momi S, et al. Reperfusion of cerebral artery thrombosis by the GPIb-VWF blockade with the Nanobody ALX-0081 reduces brain infarct size in guinea pigs. Blood. 2013 Jun 20;121(25):5088-97. DOI:10.1182/blood-2012-11-464545 |
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