Recombinant Human Tissue Kallikrein-1 for Treating Acute Ischemic Stroke and Preventing Recurrence

Area of Science:

• Neuroscience
• Pharmacology
• Cardiovascular Research

Background:

• Acute ischemic stroke necessitates novel treatments beyond revascularization.
• Bradykinin B2 receptors significantly increase in ischemic brain regions.

Purpose of the Study:

• To evaluate recombinant human tissue kallikrein-1 (rKLK1) as a therapeutic agent for acute ischemic stroke.
• To explore rKLK1's mechanism in enhancing cerebral perfusion and collateral formation.

Main Methods:

• Utilizing rKLK1, a bradykinin-producing enzyme, to target upregulated bradykinin B2 receptors.
• Investigating synergistic signaling pathways downstream of the B2 receptor for vasodilation.
• Assessing rKLK1's effects on brain perfusion, collateral recruitment, and stroke recurrence in preclinical and clinical models.

Main Results:

• rKLK1-generated bradykinin induces potent local vasodilation and increases brain perfusion.
• rKLK1 promotes both immediate vasodilation and long-term collateral formation.
• Previous trials indicated favorable outcomes, especially in patients unsuitable for mechanical thrombectomy.

Conclusions:

• rKLK1 offers a promising therapeutic strategy for acute ischemic stroke, particularly for patients not amenable to revascularization.
• rKLK1's multifaceted effects on cerebral perfusion and collateralization may reduce stroke recurrence risk.
• Further investigation, including combination therapies, is warranted for rKLK1 in stroke management.