Human tissue kallikrein in the treatment of acute ischemic stroke

Alexander-Curtis, Michelle; Pauls, Rick; Chao, Julie; Volpi, John J.; Appel, Stanley H; Bath, Philip M.; Verdoorn, Todd A.

Abstract

Acute ischemic stroke (AIS) remains a major cause of death and disability throughout the world. The most severe form of stroke results from large vessel occlusion of the major branches of the Circle of Willis. The treatment strategies currently available in Western countries for large vessel occlusion involve rapid restoration of blood flow through removal of the offending blood clot using mechanical or pharmacological means (e.g. tissue plasma activator or tPA). This review assesses prospects for a novel pharmacological approach to enhance the availability of the natural enzyme tissue kallikrein (KLK1), an important regulator of local blood flow. KLK1 is responsible for the generation of kinins (bradykinin and kallidin), which promote local vasodilation and long-term vascularization. Moreover, KLK1 has been used clinically as a direct treatment for multiple diseases associated with impaired local blood flow including AIS. A form of human KLK1 isolated from human urine is approved in the People’s Republic of China for subacute treatment of AIS. Here we review the rationale for using KLK1 as an additional pharmacological treatment for AIS by providing the biochemical mechanism as well as the human clinical data that support this approach.

Citation

Alexander-Curtis, M., Pauls, R., Chao, J., Volpi, J. J., Appel, S. H., Bath, P. M., & Verdoorn, T. A. (2019). Human tissue kallikrein in the treatment of acute ischemic stroke. Therapeutic Advances in Neurological Disorders, 12, 1-15. https://doi.org/10.1177/1756286418821918

• Journal Article Type: Review
• Acceptance Date: Oct 24, 2018
• Online Publication Date: Jan 20, 2019
• Publication Date: Jan 20, 2019
• Deposit Date: Oct 30, 2018
• Publicly Available Date: Oct 30, 2018
• Journal: Therapeutic Advances in Neurological Disorders
• Print ISSN: 1756-2856
• Electronic ISSN: 1756-2864
• Publisher: SAGE Publications
• Peer Reviewed: Peer Reviewed
• Volume: 12
• Pages: 1-15
• DOI: https://doi.org/10.1177/1756286418821918
• Public URL: https://nottingham-repository.worktribe.com/output/1211044
• Publisher URL: https://journals.sagepub.com/doi/10.1177/1756286418821918
• Contract Date: Oct 30, 2018