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.

Základní údaje

Originální název

Hidden Potential of Highly Efficient and Widely Accessible Thrombolytic Staphylokinase

Autoři

TOUL, Martin (203 Česká republika, domácí), Jan MIČAN (203 Česká republika, domácí), Veronika SLONKOVÁ (203 Česká republika, domácí), Dmitri NIKITIN (643 Rusko, domácí), Martin MAREK (203 Česká republika, domácí), David BEDNÁŘ (203 Česká republika, domácí), Jiří DAMBORSKÝ (203 Česká republika, garant, domácí) a Zbyněk PROKOP (203 Česká republika, domácí)

Vydání

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

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30210 Clinical neurology

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 8.300

Kód RIV

RIV/00216224:14310/22:00127971

Organizační jednotka

Přírodovědecká fakulta

DOI

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

UT WoS

000856392500041

Klíčová slova anglicky

alteplase; immunogenicity; kinetics; staphylokinase; stroke; thrombolysis

Štítky

rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 25. 1. 2023 12:38, Mgr. Marie Šípková, DiS.

Anotace

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.

Návaznosti

GJ20-15915Y, projekt VaV

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

Investor: Grantová agentura ČR, Studium molekulováho rozpoznávání a vývoj nových softwarových nástrojů pro identifikaci a design přístupových cest v proteinech

LX22NPO5107, projekt VaV

Název: Národní ústav pro neurologický výzkum

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Národní ústav pro neurologický výzkum, 5.1 EXCELES

Citovat

TOUL, Martin, Jan MIČAN, Veronika SLONKOVÁ, Dmitri NIKITIN, Martin MAREK, David BEDNÁŘ, Jiří DAMBORSKÝ a Zbyněk PROKOP. Hidden Potential of Highly Efficient and Widely Accessible Thrombolytic Staphylokinase. Stroke. Dallas: Lippincott Williams & Wilkins, 2022, roč. 53, č. 10, s. 3235-3237. ISSN 0039-2499. Dostupné z: 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 a Zbyněk PROKOP. Hidden Potential of Highly Efficient and Widely Accessible Thrombolytic Staphylokinase. \textit{Stroke}. Dallas: Lippincott Williams \&{} Wilkins, 2022, roč.~53, č.~10, s.~3235-3237. ISSN~0039-2499. Dostupné z: https://dx.doi.org/10.1161/STROKEAHA.122.040219.

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