Hidden Potential of Highly Efficient and Widely Accessible
Thrombolytic Staphylokinase

J 2022

Hidden Potential of Highly Efficient and Widely Accessible Thrombolytic Staphylokinase

TOUL, Martin, Jan MIČAN, Veronika SLONKOVÁ, Dmitri NIKITIN, Martin MAREK et. al.

Basic information

Original name

Hidden Potential of Highly Efficient and Widely Accessible Thrombolytic Staphylokinase

Authors

TOUL, Martin (203 Czech Republic, belonging to the institution), Jan MIČAN (203 Czech Republic, belonging to the institution), Veronika SLONKOVÁ (203 Czech Republic, belonging to the institution), Dmitri NIKITIN (643 Russian Federation, belonging to the institution), Martin MAREK (203 Czech Republic, belonging to the institution), David BEDNÁŘ (203 Czech Republic, belonging to the institution), Jiří DAMBORSKÝ (203 Czech Republic, guarantor, belonging to the institution) and Zbyněk PROKOP (203 Czech Republic, belonging to the institution)

Edition

Stroke, Dallas, Lippincott Williams & Wilkins, 2022, 0039-2499

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30210 Clinical neurology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 8.300

RIV identification code

RIV/00216224:14310/22:00127971

Organization unit

Faculty of Science

DOI

http://dx.doi.org/10.1161/STROKEAHA.122.040219

UT WoS

000856392500041

Keywords in English

alteplase; immunogenicity; kinetics; staphylokinase; stroke; thrombolysis

Abstract

V originále

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.

Links

GJ20-15915Y, research and development project

Name: Studium molekulováho rozpoznávání a vývoj nových softwarových nástrojů pro identifikaci a design přístupových cest v proteinech

Investor: Czech Science Foundation

LX22NPO5107, research and development project

Name: Národní ústav pro neurologický výzkum

Investor: Ministry of Education, Youth and Sports of the CR, 5.1 EXCELES

Citovat

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. 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.

@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.

Detailed Information on Publication Record