Integrin α9β1 Inhibitors for Ischemic Stroke Reperfusion Injury
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Solution Overview
Problem
Current treatments for ischemic stroke, such as thrombolysis and mechanical thrombectomy, lead to oxidative stress, secondary thrombosis, and vascular inflammation, causing further neuronal damage during reperfusion, with no effective intervention to minimize brain damage.
Innovation Solution
Targeting integrin α9β1 with a functional blocking inhibitor, like peptides or antibodies, to limit brain damage following reperfusion by inhibiting integrin α9β1 activity, thereby reducing cerebral thromboinflammation and improving stroke outcomes.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Speed
If thrombolysis or mechanical thrombectomy is performed to restore blood flow, then reperfusion of ischemic brain regions is achieved, but oxidative stress, secondary thrombosis, and vascular inflammation are promoted, aggravating neuronal death
Solution Approach 1:
The patent introduces integrin α9β1 inhibitors as intermediary agents that block the interaction between platelets and endothelial cells, preventing the formation of secondary thrombi and reducing vascular inflammation during reperfusion, thereby mitigating the harmful effects while maintaining blood flow restoration
Solution Approach 2:
The patent modifies the biochemical parameters of the reperfusion process by inhibiting integrin α9β1 activity, which changes the adhesion properties of platelets and leukocytes to endothelium, thereby reducing oxidative stress and inflammatory responses without compromising reperfusion efficacy
2Reliability
If antiplatelet agents are used to reduce secondary thrombosis risk, then thrombosis prevention is improved, but the risk of hemorrhagic transformation increases
Solution Approach 1:
The patent applies local quality by specifically targeting integrin α9β1 expression in vascular endothelium and platelets during the reperfusion phase, providing localized anti-thrombotic action at the site of injury without systemically affecting coagulation pathways, thereby reducing hemorrhagic transformation risk
Solution Approach 2:
The patent employs preliminary action by administering integrin α9β1 inhibitors before or during the early phase of reperfusion to prevent secondary thrombosis formation proactively, rather than treating established thrombi, which reduces the need for aggressive antiplatelet therapy that could cause bleeding
Data Source
AI summary
The invention provides a method and kits for inhibiting integrin α9β1 activity comprising contacting integrin α9β1 or a binding partner of integrin α9β1 with an isolated anti-integrin α9 inhibitor, wherein the integrin α9β1 activity is inhibited. In certain aspects, the present invention provides a novel intervention by targeting integrin α9β1 with a functional blocking inhibitor (e.g., peptides or antibodies) to limit brain damage following reperfusion after ischemic stroke.