The aptamer BT200 blocks von Willebrand factor and platelet function in blood of stroke patients

Abstract The effect of conventional anti-platelet agents is limited in secondary stroke prevention, and their effects are blunted under high shear stress in the presence of increased levels of circulating von Willebrand factor (VWF). VWF is critically involved in thrombus formation at sites of steno...

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Autores principales:	Katarina D. Kovacevic, Stefan Greisenegger, Agnes Langer, Georg Gelbenegger, Nina Buchtele, Ingrid Pabinger, Karin Petroczi, Shuhao Zhu, James C. Gilbert, Bernd Jilma
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9dfb1cccbadd4e0893278bc3fc62d9a6
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spelling	oai:doaj.org-article:9dfb1cccbadd4e0893278bc3fc62d9a62021-12-02T10:44:15ZThe aptamer BT200 blocks von Willebrand factor and platelet function in blood of stroke patients10.1038/s41598-021-82747-72045-2322https://doaj.org/article/9dfb1cccbadd4e0893278bc3fc62d9a62021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82747-7https://doaj.org/toc/2045-2322Abstract The effect of conventional anti-platelet agents is limited in secondary stroke prevention, and their effects are blunted under high shear stress in the presence of increased levels of circulating von Willebrand factor (VWF). VWF is critically involved in thrombus formation at sites of stenotic extracranial/intracranial arteries. A third generation anti-VWF aptamer (BT200) has been generated which could be useful for secondary stroke prevention. To characterize the effects of BT200 in blood of patients with large artery atherosclerosis stroke (LAA). Blood samples were obtained from 33 patients with acute stroke or transient ischemic attack to measure inhibition of VWF activity and VWF-dependent platelet function. Patients who received clopidogrel or dual antiplatelet therapy did not differ in VWF dependent platelet function tests from aspirin treated patients. Of 18 patients receiving clopidogrel with or without aspirin, only 3 had a prolonged collagen adenosine diphosphate closure time, and none of the patients had ristocetin induced aggregation in the target range. BT200 concentration-dependently reduced median VWF activity from 178 to < 3%, ristocetin induced platelet aggregation from 40U to < 10U and prolonged collagen adenosine diphosphate closure times from 93 s to > 300 s. Baseline VWF activity correlated (r = 0.86, p < 0.001) with concentrations needed to reduce VWF activity to < 20% of normal, indicating that BT200 acts in a target concentration-dependent manner. Together with a long half-life supporting once weekly administration, the safety and tolerability observed in an ongoing phase I trial, and the existence of a reversal agent, BT200 is an interesting drug candidate.Katarina D. KovacevicStefan GreiseneggerAgnes LangerGeorg GelbeneggerNina BuchteleIngrid PabingerKarin PetrocziShuhao ZhuJames C. GilbertBernd JilmaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Katarina D. Kovacevic Stefan Greisenegger Agnes Langer Georg Gelbenegger Nina Buchtele Ingrid Pabinger Karin Petroczi Shuhao Zhu James C. Gilbert Bernd Jilma The aptamer BT200 blocks von Willebrand factor and platelet function in blood of stroke patients
description	Abstract The effect of conventional anti-platelet agents is limited in secondary stroke prevention, and their effects are blunted under high shear stress in the presence of increased levels of circulating von Willebrand factor (VWF). VWF is critically involved in thrombus formation at sites of stenotic extracranial/intracranial arteries. A third generation anti-VWF aptamer (BT200) has been generated which could be useful for secondary stroke prevention. To characterize the effects of BT200 in blood of patients with large artery atherosclerosis stroke (LAA). Blood samples were obtained from 33 patients with acute stroke or transient ischemic attack to measure inhibition of VWF activity and VWF-dependent platelet function. Patients who received clopidogrel or dual antiplatelet therapy did not differ in VWF dependent platelet function tests from aspirin treated patients. Of 18 patients receiving clopidogrel with or without aspirin, only 3 had a prolonged collagen adenosine diphosphate closure time, and none of the patients had ristocetin induced aggregation in the target range. BT200 concentration-dependently reduced median VWF activity from 178 to < 3%, ristocetin induced platelet aggregation from 40U to < 10U and prolonged collagen adenosine diphosphate closure times from 93 s to > 300 s. Baseline VWF activity correlated (r = 0.86, p < 0.001) with concentrations needed to reduce VWF activity to < 20% of normal, indicating that BT200 acts in a target concentration-dependent manner. Together with a long half-life supporting once weekly administration, the safety and tolerability observed in an ongoing phase I trial, and the existence of a reversal agent, BT200 is an interesting drug candidate.
format	article
author	Katarina D. Kovacevic Stefan Greisenegger Agnes Langer Georg Gelbenegger Nina Buchtele Ingrid Pabinger Karin Petroczi Shuhao Zhu James C. Gilbert Bernd Jilma
author_facet	Katarina D. Kovacevic Stefan Greisenegger Agnes Langer Georg Gelbenegger Nina Buchtele Ingrid Pabinger Karin Petroczi Shuhao Zhu James C. Gilbert Bernd Jilma
author_sort	Katarina D. Kovacevic
title	The aptamer BT200 blocks von Willebrand factor and platelet function in blood of stroke patients
title_short	The aptamer BT200 blocks von Willebrand factor and platelet function in blood of stroke patients
title_full	The aptamer BT200 blocks von Willebrand factor and platelet function in blood of stroke patients
title_fullStr	The aptamer BT200 blocks von Willebrand factor and platelet function in blood of stroke patients
title_full_unstemmed	The aptamer BT200 blocks von Willebrand factor and platelet function in blood of stroke patients
title_sort	aptamer bt200 blocks von willebrand factor and platelet function in blood of stroke patients
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/9dfb1cccbadd4e0893278bc3fc62d9a6
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The aptamer BT200 blocks von Willebrand factor and platelet function in blood of stroke patients

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