Towards improved thrombolysis in acute ischemic stroke

Ischemic stroke is caused by a blood clot that is occluding part of the cerebral vasculature. This leads to focal impairment of the downstream blood flow and irreversible damage of the associated brain tissue. The mainstay of ischemic stroke therapy is timely recanalization of the occluded artery by targeting the occluding thrombus, either by pharmacological thrombolysis (using t-PA) or by mechanical thrombectomy. However, pharmacological thrombolysis is only available to less than 15% of patients of which less than half of patients will respond to therapy. Our recent findings on fibrin, VWF and DNA in stroke thrombi could explain why the current ‘one size fits all’ therapy aiming at only fibrinolysis via t-PA is not effective in all ischemic stroke patients. In this project, we aim to investigate the thrombolytic potential of combining t-PA (cleaving fibrin) with ADAMTS13 (cleaving VWF), DNase I (cleaving DNA) and a bispecific antibody against TAFI and PAI-1 (improving t-PA-mediated fibrinolysis).

Keywords:Stroke, Thrombus, Thrombolysis

Disciplines:Vascular diseases