Hidden Potential of Highly Efficient and Widely Accessible Thrombolytic Staphylokinase

Abstract

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.

Fibrinolytic Agents in Thromboembolic Diseases: Historical Perspectives and Approved Indications

“…[215][216][217] This combinatorial dual fibrinolytic therapy has recently been evaluated against usual intravenous alteplase therapy in a phase 2 RCT of acute ischemic stroke with 238 participants and resulted in similar rates of intracranial hemorrhage and 1-month favorable functional outcomes. 218 Furthermore, a modified nonimmunogenic recombinant form of staphylokinase has been developed in recent years 219 and has shown promising results in patients with acute ischemic stroke. 220 Nonimmunogenic staphylokinase is also currently under investigation in other thromboembolic diseases, such as PE 221 and acute limb ischemia.…”

Ursolic Acid Ameliorated Neuronal Damage by Restoring Microglia-Activated MMP/TIMP Imbalance in vitro

“…[3][4][5] However, no clinical trials were successful up to now. [6][7][8] It implies that single target therapy may not be sufficient to protect neurons. Even greater consideration should be given to finding innovative therapeutics that can successfully lower excessive neuroinflammation in cerebral I/R injury in acute ischemic stroke.…”