Phagocytosis Modulation for Aneurysm Stabilization
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Solution Overview
Problem
Current treatments for aneurysm disease, particularly abdominal aortic aneurysms, lack effective methods to slow progression or prevent rupture, with endovascular repair raising concerns about long-term stability and durability, and no medical therapies have convincingly proven to inhibit aneurysm growth or rupture.
Innovation Solution
Modulation of efferocytosis/phagocytosis pathways by administering agents that target CDKN2B, calreticulin, and CD47 to increase phagocytosis of apoptotic smooth muscle cells, stabilizing and preventing aneurysm disease, including genetic testing for 9p21 risk alleles and using agents like palbociclib and anti-CD47 antibodies to enhance phagocytic activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If endovascular repair is performed to prevent aneurysm rupture, then short-term morbidity is reduced, but long-term stability and durability are compromised
Solution Approach 1:
The patent introduces pharmaceutical agents (such as cyclooxygenase-2 inhibitors, 5-lipoxygenase inhibitors, and other anti-inflammatory drugs) as intermediaries to modulate the biological processes within the aneurysm wall. These agents mediate between the structural vulnerability of the aneurysm and the desired outcome of long-term stability by inhibiting inflammatory pathways and matrix metalloproteinase activity that contribute to wall degradation.
Solution Approach 2:
The patent employs parameter changes by administering pharmaceutical agents that alter the biochemical parameters of the aneurysm wall tissue. Specifically, the drugs change the inflammatory state, matrix composition, and cellular activity within the wall, thereby transforming the wall's mechanical and biological properties to improve long-term durability while maintaining the benefits of endovascular repair.
2Device complexity
If no medical therapies are used to slow aneurysm progression, then surgical intervention risks are avoided, but aneurysm growth and rupture risk increase
Solution Approach 1:
The patent enables the aneurysm wall to self-regulate its pathological processes by administering pharmaceutical agents that restore normal biological control mechanisms. The drugs facilitate the wall's own cellular and molecular systems to counteract inflammatory degradation and matrix breakdown, allowing the tissue to self-stabilize without requiring complex surgical interventions or continuous mechanical support.
Solution Approach 2:
Pharmaceutical agents serve as intermediaries that bridge the gap between simple administration and complex biological outcomes. These drugs translate a simple therapeutic input into coordinated biological responses within the aneurysm wall, controlling progression through modulation of inflammatory pathways, cellular activity, and extracellular matrix composition without requiring complex treatment devices or procedures.
3Adaptability or versatility
If the aneurysm wall is weakened and thinned by progressive enlargement, then adaptive remodeling occurs, but rupture risk increases
Solution Approach 1:
The patent applies parameter changes by using pharmaceutical agents to alter the biochemical and mechanical parameters of the aneurysm wall during remodeling. The drugs modify the composition and structure of the extracellular matrix, regulate cellular proliferation and apoptosis, and control inflammatory infiltration, thereby changing the wall's physical properties to maintain strength despite enlargement and adaptive remodeling.
Solution Approach 2:
Pharmaceutical agents act as intermediaries between the mechanical stresses of enlargement and the biological response of the wall tissue. These drugs mediate the remodeling process by controlling the balance between matrix synthesis and degradation, regulating cellular responses to mechanical stress, and preventing excessive thinning and weakening that would otherwise occur during adaptive enlargement.
Data Source
AI summary
In the methods of the invention, an agent that increases phagocytosis and/or efferocytosis of cellular components of coronary plaque is administered to the subject in a dose and for a period of time effective to stabilize, prevent or reduce aneurysm disease in the individual.