{"id":38401,"date":"2022-12-29T15:15:00","date_gmt":"2022-12-29T14:15:00","guid":{"rendered":"https:\/\/www.etap-lab.com\/?post_type=ressource&#038;p=38401"},"modified":"2026-10-13T16:24:17","modified_gmt":"2026-10-13T14:24:17","slug":"vwf-targeted-thrombolysis-in-experimental-ischemic-stroke-models","status":"publish","type":"ressource","link":"https:\/\/www.etap-lab.com\/en\/ressource\/vwf-targeted-thrombolysis-in-experimental-ischemic-stroke-models\/","title":{"rendered":"VWF-targeted thrombolysis to overcome rh-tPA resistance in experimental murine ischemic stroke models"},"content":{"rendered":"\n<div class=\"wp-block-columns is-layout-flex wp-container-core-columns-is-layout-7387b849 wp-block-columns-is-layout-flex\">\n<div class=\"wp-block-column is-layout-flow wp-block-column-is-layout-flow\">\n<p class=\"wp-block-paragraph\">Discover this publication with TargED Biopharmaceuticals on <strong>VWF-targeted thrombolysis to overcome rh-tPA resistance in experimental murine ischemic stroke models<\/strong>, in which studies were performed by STROK@LLIANCE on our <a href=\"https:\/\/www.etap-lab.com\/en\/cro-services\/neurovascular-stroke\/in-vivo-models\/#subcat-184\" data-type=\"modele\" data-id=\"3520\">MCA occlusion by FECl3 application in vivo model<\/a>, as well as analysis. Published in <strong>Blood (2022) 140 (26): 2844\u20132848.<\/strong> Brief Report, THROMBOSIS AND HEMOSTASIS. December 29, 2022. <\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Significant milestones since the publication:<\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li><a href=\"https:\/\/targedbiopharmaceuticals.com\/news\/targed-enters-clinic-with-phase-1-trial-of-its-groundbreaking-thrombolytic-tgd001-2\/\" target=\"_blank\" rel=\"noreferrer noopener\">TargED entered clinic with Phase 1 trial of its groundbreaking thrombolytic TGD001<\/a> (December 19, 2024).<\/li>\n\n\n\n<li>The first patients have been successfully dosed in Phase 1b\/2a proof-of-concept clinical study evaluating TGD001 as a potential treatment for acute ischemic stroke (July 16, 2026).<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Read the full article<\/strong>: DOI: <a href=\"https:\/\/doi.org\/10.1182\/blood.2022016342\">https:\/\/doi.org\/10.1182\/blood.2022016342<\/a><\/p>\n\n\n\n<p class=\"wp-block-paragraph\">K<strong><em>eypoints:<\/em><\/strong><\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Microlyse is noninferior to rh-tPA when AIS is driven by fibrin-rich thrombi, but superior in AIS driven by platelet-rich thrombi.<\/li>\n\n\n\n<li>VWF-targeted plasminogen activation overcomes the intrinsic resistance of platelet-rich thrombi against rh-tPA\u2013mediated thrombolysis.<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><mark style=\"background-color:rgba(0, 0, 0, 0)\" class=\"has-inline-color has-blue-light-color\"><em><strong>Keywords:<\/strong><\/em> ischemic stroke; microlyse, thrombolytic agent, fibrin-rich thrombi, platelet-rich thrombi, cerebral reperfusion.<\/mark><\/p>\n\n\n\n<div style=\"height:30px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n\n<div class=\"wp-block-buttons is-layout-flex wp-block-buttons-is-layout-flex\">\n<div class=\"wp-block-button is-style-primary\"><a class=\"wp-block-button__link wp-element-button\" href=\"https:\/\/www.etap-lab.com\/en\/contact\/\">CONTACT AN EXPERT NOW<\/a><\/div>\n<\/div>\n\n\n\n<div style=\"height:30px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Authors<\/strong>: Marc V. A. van Moorsel 1 2, Steven de Maat 1 2, Kristof Vercruysse 2, Esther M. van Leeuwen 3, Charl\u00e8ne Jacqmarcq 4, Thomas Bonnard, Denis Vivien4 5, H. Bart van der Worp 6, Rick M. Dijkhuizen 3, Coen Maas 1 2.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Affiliated<\/strong>:<\/p>\n\n\n\n<ul class=\"wp-block-list\">\n<li>1. Central Diagnostic Laboratory Research, University Medical Center Utrecht and Utrecht University, Utrecht, The Netherlands. <\/li>\n\n\n\n<li>2. <a href=\"https:\/\/targedbiopharmaceuticals.com\/app\/uploads\/2024\/01\/VWF-targeted-thrombolysis-to-overcome-rh-tPA-resistance-in-experime_2022_Blo.pdf\">TargED Biopharmaceuticals<\/a>, Utrecht, The Netherlands. <\/li>\n\n\n\n<li>3. Biomedical MR Imaging and Spectroscopy Group, Center for Image Sciences, University Medical Center Utrecht and Utrecht University, Utrecht, The Netherlands. <\/li>\n\n\n\n<li>4. UNICAEN, INSERM U1237, Physiopathology and Imaging of Neurological Disorders (PhIND), Cyceron, Institut Blood and Brain @ Caen-Normandie (<a href=\"https:\/\/www.bb-c.fr\/partenaire\/etap-lab\/\" target=\"_blank\" rel=\"noreferrer noopener\">BB@C<\/a>), Normandie University, Caen, France. <\/li>\n\n\n\n<li>5. Department of Clinical Research, Caen Normandie University Hospital, Caen, France. <\/li>\n\n\n\n<li>6. Department of Neurology and Neurosurgery, Brain Center, University Medical Center Utrecht and Utrecht University, Utrecht, The Netherlands<\/li>\n<\/ul>\n\n\n\n<p class=\"wp-block-paragraph\"><strong>Acknowledgments<\/strong>: The authors thank <strong><mark style=\"background-color:rgba(0, 0, 0, 0)\" class=\"has-inline-color has-blue-light-color\">Strok@lliance (Caen, France)<\/mark><\/strong>, and specifically Annelise Letourneur and Nicolas Violle <strong><mark style=\"background-color:rgba(0, 0, 0, 0)\" class=\"has-inline-color has-blue-light-color\">for performing the in vivo experiments and analyses<\/mark><\/strong>.<\/p>\n\n\n\n<div style=\"height:40px\" aria-hidden=\"true\" class=\"wp-block-spacer\"><\/div>\n\n\n\n<p class=\"wp-block-paragraph\"><strong><mark style=\"background-color:rgba(0, 0, 0, 0)\" class=\"has-inline-color has-blue-light-color\">ABSTRACT:<\/mark><\/strong><\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong><em>Background<\/em><\/strong><\/p>\n\n\n\n<h2 class=\"wp-block-heading has-m-font-size\"><strong>Microlyse, a Novel Thrombolytic Agent for Acute Ischemic Stroke<\/strong><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">Recombinant human tissue plasminogen activator (rh-tPA) is an important thrombolytic agent for treatment of acute ischemic stroke. It requires fibrin binding for plasminogen activation. In contrast, Microlyse, a novel thrombolytic agent, requires von Willebrand factor (VWF) binding for plasminogen activation.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><strong><em>Methods<\/em><\/strong><\/p>\n\n\n\n<h2 class=\"wp-block-heading has-m-font-size\"><strong>Comparison of Microlyse and rh-tPA in Experimental Stroke Models<\/strong><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">We compared rh-tPA with Microlyse, administered 20 minutes after inducing thrombosis, in 2 randomized blinded <a href=\"https:\/\/www.etap-lab.com\/en\/cro-services\/neurovascular-stroke\/in-vivo-models\/#subcat-184\">acute ischemic stroke mouse models<\/a>. Thrombosis was induced in the middle cerebral artery with different experimental triggers. Where thrombin infusion generates fibrin-rich thrombi, topical FeCl3 application generates platelet-rich thrombi.<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><\/p>\n\n\n\n<h2 class=\"wp-block-heading has-m-font-size\"><strong>Improved Reperfusion and Reduced Lesion Volume in Fibrin-Rich Thrombi<\/strong><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">In the fibrin-rich model, both rh-tPA and Microlyse increased cortical reperfusion (determined by laser speckle imaging) 10 minutes after therapy administration (35.8\u00a0\u00b1 17.1%; <em>P<\/em>\u00a0= .001 39.3\u00a0\u00b1 13.1%; <em>P<\/em>\u00a0&lt; .0001; 15.6\u00a0\u00b1 7.5%, respectively, vs vehicle). In addition, both thrombolytic agents reduced cerebral lesion volume (determined by magnetic resonance imaging) after 24 hours (18.9\u00a0\u00b1 11.2 mm<sup>3<\/sup>; <em>P<\/em>\u00a0= .033; 16.1\u00a0\u00b1 13.9 mm<sup>3<\/sup>; <em>P<\/em>\u00a0= .018; 26.6\u00a0\u00b1 5.6 mm<sup>3<\/sup>, respectively, vs vehicle).<\/p>\n\n\n\n<p class=\"wp-block-paragraph\"><\/p>\n\n\n\n<h2 class=\"wp-block-heading has-m-font-size\"><strong>Microlyse Shows Benefits in Platelet-Rich Thrombi<\/strong><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">In the platelet-rich model, neither rh-tPA nor Microlyse increased cortical reperfusion 10 minutes after therapy (7.6\u00a0\u00b1 8.8%; <em>P<\/em>\u00a0= .216; 16.3\u00a0\u00b1 13.9%; <em>P<\/em>\u00a0= .151; 10.1\u00a0\u00b1 7.9%, respectively, vs vehicle). However, Microlyse, but not rh-tPA, decreased cerebral lesion volumes (13.9\u00a0\u00b1 11.4 mm<sup>3<\/sup>; <em>P<\/em>\u00a0&lt; .001; 23.6\u00a0\u00b1 11.1 mm<sup>3<\/sup>; <em>P<\/em>\u00a0= .188; 30.3\u00a0\u00b1 10.9 mm<sup>3<\/sup>, respectively, vs vehicle).<\/p>\n<\/div>\n<\/div>\n\n\n\n<p class=\"wp-block-paragraph\"><strong><em>Results<\/em><\/strong><\/p>\n\n\n\n<h2 class=\"wp-block-heading has-m-font-size\"><strong>Broad Therapeutic Potential of Microlyse for Ischemic Stroke<\/strong><\/h2>\n\n\n\n<p class=\"wp-block-paragraph\">These findings support broad applicability of Microlyse in ischemic stroke, irrespective of the thrombus composition.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Discover this publication with TargED Biopharmaceuticals on VWF-targeted thrombolysis to overcome rh-tPA resistance in experimental murine ischemic stroke models, in which studies were performed by STROK@LLIANCE on our MCA occlusion by FECl3 application in vivo model, as well as analysis. Published in Blood (2022) 140 (26): 2844&ndash;2848. Brief Report, THROMBOSIS AND HEMOSTASIS. December 29, 2022. [&hellip;]<\/p>\n","protected":false},"featured_media":38151,"template":"","meta":{"_acf_changed":false},"categorie-de-ressource":[235],"marque-de-ressource":[242],"class_list":["post-38401","ressource","type-ressource","status-publish","has-post-thumbnail","hentry","categorie-de-ressource-publications","marque-de-ressource-strokalliance"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v28.7 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>VWF-targeted thrombolysis to overcome rh-tPA resistance in experimental murine ischemic stroke models - ETAP-LAB<\/title>\n<meta name=\"description\" content=\"Publication exploring Microlyse preclinical results (compared with rh-tPA), a next-generation thrombolytic clot-busting drug, developped by TargED.\" \/>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.etap-lab.com\/en\/ressource\/vwf-targeted-thrombolysis-in-experimental-ischemic-stroke-models\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"VWF-targeted thrombolysis to overcome rh-tPA resistance in experimental murine ischemic stroke models - 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