Human tissue kallikrein in the treatment of acute ischemic stroke.
| Autor: | Alexander-Curtis M; DiaMedica Therapeutics, 2 Carlson Parkway, Minneapolis, MN 55447, USA., Pauls R; DiaMedica Therapeutics, Minneapolis, MN, USA., Chao J; Medical University of South Carolina, Department of Biochemistry and Molecular Biology, Charleston, SC, USA., Volpi JJ; Houston Methodist, Stanley H. Appel Department of Neurology, Houston, TX, USA., Bath PM; Stroke Trials Unit, University of Nottingham, City Hospital Campus, Nottingham, UK., Verdoorn TA; DiaMedica Therapeutics, Minneapolis, MN, USA. |
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| Jazyk: | angličtina |
| Zdroj: | Therapeutic advances in neurological disorders [Ther Adv Neurol Disord] 2019 Jan 20; Vol. 12, pp. 1756286418821918. Date of Electronic Publication: 2019 Jan 20 (Print Publication: 2019). |
| DOI: | 10.1177/1756286418821918 |
| Abstrakt: | 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; 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. Competing Interests: Conflict of interest statement: Dr Alexander, Mr Pauls, and Dr Verdoorn are employees of DiaMedica Therapeutics, which funded the clinical trial cited using DM199. Dr Chao, Dr Bath and Dr Volpi are scientific advisors to DiaMedica Therapeutics, have received honoraria from the company and hold stock options. |
| Databáze: | MEDLINE |
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