Cobinamide Therapy to Reduce Oxidative Stress in Aortic Aneurysms
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Aortic aneurysms and dissections remain high in morbidity and mortality despite surgical improvements, particularly in thoracic aortic aneurysms and dissections (TAAD), with underlying pathology involving elastin fiber fragmentation, smooth muscle cell loss, and collagen accumulation, and genetic mutations affecting proteins like TGF-β signaling and SMC contractile apparatus components.
Innovation Solution
Administration of cobinamide, its derivatives, or salts to treat aortic diseases by inhibiting oxidative stress, downregulating Hif-1α/Vegfa or Tgfb1/Ctgf pathways, and inhibiting PKG activity, thereby preventing aortic dilation and SMC loss.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Strength
If surgical repair methods are used for aortic aneurysms, then structural integrity is improved, but morbidity and mortality remain high
Solution Approach 1:
The patent applies preliminary action by administering cobinamide before aortic surgery to reduce oxidative stress and prevent elastin fiber fragmentation. This pre-treatment approach addresses the underlying pathological processes that contribute to poor surgical outcomes, thereby improving patient prognosis while maintaining the necessary structural integrity repairs
Solution Approach 2:
Cobinamide serves as an intermediary substance that mediates between the surgical intervention and the aortic tissue. It reduces oxidative stress and prevents elastin fragmentation, creating a more favorable condition for surgical repair and improving overall treatment reliability without replacing the surgical procedure
2Reliability
If β-adrenergic or angiotensin receptor blockers are used for blood pressure control, then prognosis is modestly improved, but aortic pathology progression continues
Solution Approach 1:
The patent changes the therapeutic parameter from blood pressure control alone to include oxidative stress reduction. By administering cobinamide, the treatment addresses a different pathological parameter (oxidative stress and elastin fragmentation) that complements blood pressure control, thereby improving prognosis while stabilizing aortic tissue composition
Solution Approach 2:
The treatment approach is segmented into two distinct components: blood pressure control (existing therapy) and oxidative stress reduction (new cobinamide therapy). This segmentation allows each treatment to address specific pathological aspects independently, with cobinamide targeting elastin fragmentation and oxidative stress while blood pressure medications manage hemodynamic factors
3Ease of operation
If PKG-activating drugs are used long-term, then vasodilation and SMC differentiation are improved, but risk for acute aortic dissections increases
Solution Approach 1:
The patent converts the harmful effect of excessive PKG activation (increased dissection risk) into a beneficial outcome by using cobinamide to counterbalance it. Cobinamide reduces oxidative stress and prevents elastin fragmentation, which offsets the detrimental effects of PKG-activating drugs, allowing them to be used with reduced risk
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
Cobinamide effectively inhibits elastin fiber breaks, reduces oxidative stress, and maintains aortic integrity by inhibiting JNK activation and SMC loss, thus reducing aortic dilation and dissections.
Implementation Method 1
cobinamide... is administered orally... the composition comprising an anti-oxidant to lower reactive oxygen species
Data Source
AI summary
Compositions and methods for treatment of aortic disease in a subject in need comprising an effective amount of cobinamide. Aortic diseases include for example aortic aneurysm, aortic dissection, or aortic dilation. Aortic disease can be caused for example by Marfan syndrome or oxidative stress.