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Project

Towards Improved Thrombolysis in Acute Ischemic Stroke: an Interdisciplinary Approach Combining Computer Systems Biology With Novel Therapeutic Targets

Ischemic stroke is a devastating disease, representing one of the leading causes of death and disability worldwide. Occlusion of a major or multiple smaller intracerebral arteries by blood thrombi leads to focal impairment or cessation of the downstream blood flow, resulting in irreversible damage of the associated brain tissue. Rapid thrombolysis using tissue-plasminogen activator (t-PA, which promotes cleavage of fibrin in the thrombus) is currently the only approved therapeutic treatment option, but has many serious limitations, which makes t-PA treatment only available to less than 10% of patients. Most importantly, even in patients that receive t-PA, its efficacy is limited as it leads to successful recanalization only in less than half of those patients that receive the drug. We recently discovered several novel therapeutic strategies that could overcome the limitations of t-PA therapy and that could significantly improve the efficacy and safety of  thrombolysis in ischemic stroke.  In this research proposal, we aim to combine our novel pathophysiological insights with advanced computational systems biology (expertise from our Russian partner) to further advance our understanding of the intricate pathways of thrombolysis and to generate powerful prediction models that identify the most efficient trombolytic treatment regimens (combining more than one of our novel therapeutic strategies) that can guide future preclinical and translational experimental research.
 

Date:1 Jan 2020 →  31 Dec 2022
Keywords:Ischemic stroke, thrombolysis, computer systems biology
Disciplines:Vascular diseases, Modelling and simulation