Selexipag Plaque Stabilization for Atherosclerosis Treatment
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Solution Overview
Problem
Current treatments for atherosclerosis, such as statins and PCSK9 inhibitors, are not effective in all patients and can cause adverse side effects, while existing therapies do not directly target the atherosclerotic plaque, leaving a need for safe and efficient therapies that prevent plaque formation and rupture.
Innovation Solution
Selexipag is used to inhibit atherosclerotic plaque lipid core formation, reduce plaque content, enhance HDL-mediated cholesterol efflux, and stabilize plaques by inhibiting vascular smooth muscle cells from internalizing LDL, thereby preventing plaque rupture and thrombosis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If statins and PCSK9 inhibitors are used to treat atherosclerosis, then LDL-C levels are reduced, but the treatments are not effective in all patients and can cause adverse side effects
Solution Approach 1:
The patent changes the therapeutic parameter from LDL-C lowering to direct plaque stabilization. Selexipag targets the EP2 receptor to modify plaque composition and stability parameters, including increasing collagen content and decreasing lipid core size, thereby treating atherosclerosis through a different physiological parameter rather than cholesterol levels.
Solution Approach 2:
Selexipag acts as an intermediary compound that binds to the EP2 receptor on vascular smooth muscle cells and inflammatory cells within the plaque. This intermediary action triggers downstream signaling pathways that stabilize the plaque without requiring LDL-C reduction, thus avoiding the side effects associated with statins and PCSK9 inhibitors.
2Reliability
If existing therapies are used, then cardiovascular risk is reduced indirectly, but they do not directly target the atherosclerotic plaque
Solution Approach 1:
The patent segments the atherosclerosis treatment approach by specifically targeting the plaque structure itself rather than systemic cholesterol metabolism. Selexipag acts locally on the plaque components (smooth muscle cells, inflammatory cells, extracellular matrix) to stabilize the lesion, providing direct plaque-targeted therapy with a relatively simple mechanism of EP2 receptor activation.
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
Selexipag effectively reduces atherosclerotic plaque lipid core content by at least 10-50%, stabilizes plaques, and increases cholesterol efflux by at least 10-50%, thereby reducing the risk of plaque rupture and associated cardiovascular events.
Implementation Method 1
One of the main functions of HDL is to promote cholesterol efflux (CE) from peripheral tissues and atherosclerotic plaques and to transport it to the liver where it will be converted into bile acids excreted in faeces as bile salts.
Implementation Method 2
Selexipag stabilizes plaques by inhibiting vascular smooth muscle cells from internalizing LDL
Data Source
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AI summary
The present invention relates to the use of Selexipag to treat and prevent atherosclerosis, and resulting atherosclerotic cardiovascular diseases. In some aspects, the Selexipag prevents plaque formation, inhibits plaque development, reduces such plaque, reduces lipid core, prevents plaque rupture, decreases the susceptibility of plaque to rupture, and prevent thrombus associated with such plaque rupture. In some aspects, the Selexipag prevents smooth muscle cells from internalising cholesterol, and stimulates cholesterol efflux from the arterial wall.