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@article{2246441,
author = {Toul, Martin and Mičan, Jan and Slonková, Veronika and Nikitin, Dmitri and Marek, Martin and Bednář, David and Damborský, Jiří and Prokop, Zbyněk},
article_location = {Dallas},
article_number = {10},
doi = {http://dx.doi.org/10.1161/STROKEAHA.122.040219},
keywords = {alteplase; immunogenicity; kinetics; staphylokinase; stroke; thrombolysis},
language = {eng},
issn = {0039-2499},
journal = {Stroke},
title = {Hidden Potential of Highly Efficient and Widely Accessible Thrombolytic Staphylokinase},
url = {https://www.ahajournals.org/doi/10.1161/STROKEAHA.122.040219},
volume = {53},
year = {2022}
}
TY - JOUR
ID - 2246441
AU - Toul, Martin - Mičan, Jan - Slonková, Veronika - Nikitin, Dmitri - Marek, Martin - Bednář, David - Damborský, Jiří - Prokop, Zbyněk
PY - 2022
TI - Hidden Potential of Highly Efficient and Widely Accessible Thrombolytic Staphylokinase
JF - Stroke
VL - 53
IS - 10
SP - 3235-3237
EP - 3235-3237
PB - Lippincott Williams & Wilkins
SN - 00392499
KW - alteplase
KW - immunogenicity
KW - kinetics
KW - staphylokinase
KW - stroke
KW - thrombolysis
UR - https://www.ahajournals.org/doi/10.1161/STROKEAHA.122.040219
N2 - Stroke burden is substantially increasing but current therapeutic drugs are still far from ideal. Here we highlight the vast potential of staphylokinase as an efficient, fibrin-selective, inexpensive, and evolvable thrombolytic agent. The emphasis is escalated by new recent findings. Staphylokinase nonimmunogenic variant was proven noninferior to alteplase in a clinical trial, with decreased risk of intracranial hemorrhage and the advantage of single bolus administration. Furthermore, our detailed kinetic analysis revealed a new staphylokinase limiting bottleneck whose elimination might provide up to 1000-fold higher activity than the clinically approved alteplase. This knowledge of limitations unlocks new possibilities for improvements that are now achievable by the community of protein engineers who have the required expertise and are ready to transform staphylokinase into a powerful molecule. Collectively, the noninferiority and safety of nonimmunogenic staphylokinase together with the newly identified effectivity limitation make staphylokinase a perfect candidate for further exploration, modification, and advancement to make it the next-generation widely accessible thrombolytic drug effectively treating stroke all around the world, including middle- and low-income countries.
ER -
TOUL, Martin, Jan MIČAN, Veronika SLONKOVÁ, Dmitri NIKITIN, Martin MAREK, David BEDNÁŘ, Jiří DAMBORSKÝ and Zbyněk PROKOP. Hidden Potential of Highly Efficient and Widely Accessible Thrombolytic Staphylokinase. \textit{Stroke}. Dallas: Lippincott Williams \&{} Wilkins, 2022, vol.~53, No~10, p.~3235-3237. ISSN~0039-2499. Available from: https://dx.doi.org/10.1161/STROKEAHA.122.040219.
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