Recombinant Apyrase and P2Y12 Inhibitor Combination for Ischemic Events
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Solution Overview
Problem
Current treatments for ischemic events such as myocardial infarction and acute ischemic stroke, despite using P2Y12 receptor inhibitors, still pose a risk of recurring events and increased bleeding risks, with limited cardioprotective benefits and inefficiencies in reducing infarct size and improving heart function.
Innovation Solution
Administering a recombinant apyrase protein, specifically AZD3366, in conjunction with a P2Y12 inhibitor like ticagrelor to enhance cardioprotective effects while minimizing bleeding risks, by modulating platelet activity and increasing extracellular adenosine levels.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If P2Y12 receptor inhibitors are used to prevent thrombotic events, then platelet inhibition and thrombosis prevention are improved, but bleeding risk increases
Solution Approach 1:
The patent combines two different therapeutic mechanisms: apyrase (which depletes extracellular ATP and ADP) and P2Y12 inhibitors (which block platelet activation). This combination provides synergistic anti-thrombotic protection while allowing for potentially lower doses of each agent, thereby reducing bleeding risk compared to high-dose monotherapy
Solution Approach 2:
Apyrase acts as an intermediary that depletes extracellular nucleotides (ATP and ADP) before they can activate platelets. This creates a dual-mechanism approach where apyrase reduces the availability of platelet-activating signals, complementing the P2Y12 receptor blockade and providing more controlled anti-thrombotic activity
2Reliability
If intensity of P2Y12 inhibitor treatment is increased to reduce thrombotic events, then thrombosis prevention is improved, but bleeding risk increases further
Solution Approach 1:
The patent employs partial action by using apyrase to deplete a portion of extracellular ATP and ADP, complementing the P2Y12 inhibitor's partial blockade of platelet activation. This multi-modal approach achieves sufficient anti-thrombotic protection without requiring maximal intensification of a single agent, thereby limiting excessive bleeding risk
3Ease of operation
If single-agent P2Y12 inhibitor therapy is used, then treatment simplicity is maintained, but cardioprotective benefits are limited
Solution Approach 1:
The patent merges apyrase therapy with P2Y12 inhibitor therapy to achieve enhanced cardioprotection. Apyrase provides additional benefits by depleting extracellular ATP and ADP, reducing inflammation, and preventing thrombosis through mechanisms distinct from P2Y12 inhibition, thereby improving overall cardioprotective benefits while maintaining a relatively simple two-agent regimen
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The combination of recombinant apyrase protein and P2Y12 inhibitor significantly reduces infarct size, improves cardiac function, and maintains low bleeding risks, offering a net clinical benefit by targeting the same biological pathway, unlike traditional single-agent therapies.
Implementation Method 1
Apyrases (ecto-ATP diphosphohydrolases) constitute a group of enzymes catalysing metabolism of ATP to ADP and ADP to AMP
Implementation Method 2
The AMP produced by apyrase-induced hydrolysis of ATP and ADP is converted into adenosine by the ubiquitously expressed extracellular CD73/ecto-5'-nucleotidase
Implementation Method 3
Apyrase reduces ATP and ADP interaction with all three platelet P2 receptors (P2X1, P2Y1 and P2Y12), therefore acting to inhibit platelet activation and recruitment
Data Source
AI summary
The present invention relates to methods for treating ischemic events in a patient, especially ST-segment elevation myocardial infarction and acute ischemic stroke, by administrating a recombinant apyrase protein in conjunction with a P2Y12 inhibitor.