-- The latest data from the World Stroke Organization (WSO) indicate that approximately 12 million people experience a new stroke each year worldwide, with around 7.3 million deaths. This means that more than 20 people have a stroke every minute, with a lifetime risk of stroke approaching 1 in 4 individuals above age 25. Stroke is a leading cause of disability worldwide; therefore, its prevention and control remain an urgent priority. October 29, 2026, marks the 21st World Stroke Day, with this year's theme, "Every Minute Counts." When stroke occurs, recognizing the signs and seeking emergency help immediately through "#ActFAST" is a critical first step. For acute ischemic stroke (AIS), early restoration of effective cerebral perfusion is central to treatment. Remarkably, there has been no new pharmaceutical agent widely adopted worldwide for AIS in over 25 years1. Given the narrow therapeutic window and low utilization rate of reperfusion therapies, approaches beyond vessel recanalization are of significant interest. Tissue kallikrein (TK) supplementation may offer a better-tolerated option for a broader range of AIS patients and is increasingly attracting significant attention from the global medical community.
What Is TK Supplementation?
AIS frequently represents the end-stage clinical event of underlying cardiovascular diseases, characterized by chronic hyperactivity of the renin-angiotensin system (RAS). The RAS and the kallikrein-kinin system (KKS) function counterbalance each other to maintain physiological homeostasis. TK, a key upstream enzyme in the RAS-KKS axis, mediates its biological actions through the bradykinin B2 receptor. Following AIS, compensatory increases in TK and B2 receptor activity may provide endogenous protection. However, endogenous TK compensation may be insufficient, and the increases in TK activity and B2 receptor levels may not be proportionate, providing a rationale for exogenous TK supplementation.
As a protective factor, TK acts throughout the processes of compensation, decompensation, and neurological repair—from targeting collateral circulation and restoring perfusion, to preserving vascular endothelial function, improving neurovascular coupling, and alleviating neurological injury through multiple pathways, and ultimately supporting vascular function and tissue repair. These multifaceted mechanisms provide a rationale for TK supplementation as a new therapeutic approach in AIS.
Evidence to Date: Potential Benefits of TK Supplementation
TK supplementation includes human urinary kallidinogenase (HUK) and the investigational agent DM199. HUK is a human-derived form of tissue kallikrein-1 (KLK1) that has been tested as a treatment in thousands of patients with AIS and has received approval for this indication in China1. Rinvecalinase alfa (also known as DM199) is a recombinant KLK1 with a molecular structure similar to endogenous KLK1 and HUK1. A post hoc analysis from the randomized, double-blind, placebo-controlled Phase 2 ReMEDy1 demonstrated that among patients who did not undergo mechanical thrombectomy, DM199 was associated with a 22% higher rate of excellent outcome (NIHSS ≤1) at 90 days than placebo (36% vs. 14%)2; the 90-day incidence of stroke recurrence was 2.2%2, comparable to the 2.5% reported in the prospective, multicenter Phase 4 RESK study regarding HUK3.
In addition to neurological recovery and prevention of recurrent stroke, TK combined with endovascular therapy (EVT) may further improve functional outcomes. Post hoc analyses of two large randomized controlled trials found that, among patients with AIS who underwent EVT, TK use was associated with favorable 90-day outcomes and significantly lower 90-day mortality (18.5% vs. 11.3%), as well as significantly reduced symptomatic intracranial hemorrhage (8.6% vs. 2.0%)4. A propensity score-matched post hoc analysis of 6,530 patients with AIS in CASTOR found that, compared with no TK treatment, TK was associated with significantly better 3-month functional outcomes in patients with mild-to-moderate AIS5. Based on these findings, a special report in Stroke noted that TK significantly improved cerebral perfusion, extended the treatment window, and reduced recurrence risk in patients for whom reperfusion therapy was unsuitable or unsuccessful1.
Earlier Intervention: TK Supplementation Supports Stroke Prevention and Control
Targeting risk factors is fundamental to stroke prevention and control. Hypertension and diabetes are major risk factors for stroke. Retrospective studies suggest that metabolic syndrome, including hypertension and diabetes, downregulates TK levels to impair endothelial function and worsen stroke outcomes6. Reduced TK levels have also been observed across conditions including AIS, hypertension, and diabetes. These findings suggest that TK supplementation could have relevance beyond stroke and may contribute to better regulation of blood pressure and glucose to address needs shared by these conditions. Additionally, plasma TK levels also have potential value for stroke risk assessment.
Conclusion
For patients with stroke, every minute can affect survival and long-term outcomes. TK supplementation has several features relevant to AIS treatment, capable of reducing infarct size, improving neurological function, and minimizing brain injury. It may offer a potentially safe and effective adjunctive option for a broader stroke population while easing families' financial and caregiving burdens.
References
1. Kasner SE, et al. Stroke. 2025 Mar;56 (3):745-753.
2. Campbell BC, et al. International Journal of Stroke. 2026;21(6):861-870.
3. Ni J, et al. CNS Neurosci Ther. 2021 Dec;27(12):1493-1503.
4. Wang M, et al. J Cereb Blood Flow Metab. 2024;44 (9):1565-1576.
5. Huang D, et al. Stroke. 2026 Jan;57(1):63-76.
6. Ruan H, et al. MedComm (2020). 2025 Nov 26;6(12):e70506.
Contact Info:
Name: Yawen Guo
Email: Send Email
Organization: Kingyee (Beijing) Co., Ltd.,
Phone: 15120030195
Website: https://www.medlive.cn/
Release ID: 89207763
Google
RSS