sEH Inhibitors Stabilize EETs to Treat Cardiomyopathy
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Solution Overview
Problem
Current pharmacologic therapies for cardiomyopathy and associated cardiac arrhythmias are ineffective and carry significant side effects, with limited options for inhibiting or reversing cardiac hypertrophy and arrhythmias, particularly in conditions like dilated cardiomyopathy and hypertrophic cardiomyopathy.
Innovation Solution
Administration of cis-epoxyeicosantrienoic acids (EETs) or inhibitors of soluble epoxide hydrolase (sEH), alone or in combination, to inhibit cardiomyopathy and cardiac arrhythmias, including the use of specific compounds like adamantyl dodecyl urea derivatives and nucleic acids to reduce sEH expression.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current pharmacologic therapies are used for cardiomyopathy and cardiac arrhythmias, then treatment is provided, but the therapies are ineffective and carry significant side effects
Solution Approach 1:
The patent changes the biochemical parameter by inhibiting soluble epoxide hydrolase (sEH), thereby increasing the levels of cis-epoxyeicosatrienoic acids (EETs) in the body. This parameter change leads to improved cardiac function and reduced arrhythmias without the harmful side effects of conventional antiarrhythmic drugs. The mechanism involves sEH inhibition preventing the breakdown of EETs, which are protective lipid mediators that regulate cardiac hypertrophy and arrhythmia.
2Reliability
If implantable defibrillators are used to treat high-risk patients, then cardiac arrhythmias are controlled, but the treatment is costly and invasive
Solution Approach 1:
The patent replaces the mechanical/electrical system of implantable defibrillators with a pharmacological system. By administering sEH inhibitors and EETs, the treatment works through biochemical mechanisms to stabilize cardiac rhythm and prevent arrhythmias, eliminating the need for invasive electrical devices and their associated costs and complications.
3Reliability
If available antiarrhythmic drugs are used, then cardiac arrhythmias are treated, but the drugs carry high risk of proarrhythmias and other systemic side effects
Solution Approach 1:
The patent converts the harmful effect of sEH activity (which breaks down protective EETs) into a benefit by inhibiting sEH. This inhibition preserves and increases EET levels, which are naturally protective against arrhythmias and cardiac hypertrophy. The approach uses the body's own protective lipid mediators rather than introducing foreign drugs with harmful side effects.
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 solution effectively inhibits or reverses cardiac hypertrophy and arrhythmias, reducing the risk of sudden cardiac death by stabilizing EETs and other epoxide-containing lipids, offering a less invasive and cost-effective alternative to existing treatments.
Implementation Method 1
sEH inhibitors increase the levels of EETs and other epoxide-containing lipids in the body. sEH is an enzyme that hydrolyzes EETs to DHETs.
Data Source
AI summary
The invention provides methods for inhibiting cardiomyopathy and for inhibiting cardiac arrhythmia, by administering to an individual in need thereof a cis-epoxyeicosantrienoic acid, an inhibitor of soluble epoxide hydrolase (sEH), or both. In some embodiments, the method comprises administering to the individual a nucleic acid encoding an inhibitor of sEH. Cardiomyopathies treatable by the methods of the invention include cardiac hypertrophy and dilated cardiomyopathy.