Development and Testing of Thrombolytics in Stroke

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Authors

NIKITIN Dmitri CHOI Seungbum MIČAN Jan TOUL Martin RYU Wi-Sun DAMBORSKÝ Jiří MIKULÍK Robert KIM Dong-Eog

Year of publication 2021
Type Article in Periodical
Magazine / Source JOURNAL OF STROKE
MU Faculty or unit

Faculty of Science

Citation
Web https://www.j-stroke.org/journal/view.php?doi=10.5853/jos.2020.03349
Doi http://dx.doi.org/10.5853/jos.2020.03349
Keywords Stroke; Thrombolytic therapy; Tissue plasminogen activator; Protein engineering
Attached files
Description Despite recent advances in recanalization therapy, mechanical thrombectomy will never be a treatment for every ischemic stroke because access to mechanical thrombectomy is still limited in many countries. Moreover, many ischemic strokes are caused by occlusion of cerebral arteries that cannot be reached by intra-arterial catheters. Reperfusion using thrombolytic agents will therefore remain an important therapy for hyperacute ischemic stroke. However, thrombolytic drugs have shown limited efficacy and notable hemorrhagic complication rates, leaving room for improvement. A comprehensive understanding of basic and clinical research pipelines as well as the current status of thrombolytic therapy will help facilitate the development of new thrombolytics. Compared with alteplase, an ideal thrombolytic agent is expected to provide faster reperfusion in more patients; prevent re-occlusions; have higher fibrin specificity for selective activation of clot-bound plasminogen to decrease bleeding complications; be retained in the blood for a longer time to minimize dosage and allow administration as a single bolus; be more resistant to inhibitors; and be less antigenic for repetitive usage. Here, we review the currently available thrombolytics, strategies for the development of new clot-dissolving substances, and the assessment of thrombolytic efficacies in vitro and in vivo.

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