Oxygen-Modified Omega-3 Fatty Acids for NASH Fibrosis
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Solution Overview
Problem
Current treatments for non-alcoholic steatohepatitis (NASH) and alcoholic steatohepatitis (ASH) are inadequate in effectively addressing hepatic fibrosis and inflammation, which are critical factors in disease progression and associated with increased morbidity and mortality.
Innovation Solution
A combination therapy comprising an oxygen-containing structurally modified fatty acid, such as 2-(((5Z,8Z,11Z,14Z,17Z)-icosa-5,8,11,14,17-pentaen-1-yl)oxy)butanoic acid, in conjunction with a glucagon-like peptide 1 (GLP-1) receptor agonist, an acetyl-CoA carboxylase (ACC) inhibitor, and a farnesoid X receptor (FXR) agonist, is administered to target multiple pathways contributing to these diseases, reducing hepatic steatosis, inflammation, and fibrosis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If omega-3 fatty acids are used to treat NASH, then hepatosteatosis is reduced, but the treatment is insufficient for reversing pronounced histological and inflammatory changes
Solution Approach 1:
The patent modifies the chemical structure of omega-3 fatty acids by introducing oxygen-containing groups (hydroxyl, carbonyl, or carboxyl) at specific positions (α, β, or γ positions relative to the carboxyl group). This structural modification transforms the fatty acid into a more potent derivative that can effectively reverse pronounced histological and inflammatory changes in NASH, while maintaining the ability to reduce hepatosteatosis.
Solution Approach 2:
The invention creates composite therapeutic molecules by combining the hydrophobic fatty acid chain (which targets hepatic steatosis) with polar oxygen-containing functional groups (which address inflammation and fibrosis). This composite structure enables the single molecule to act on multiple pathological pathways simultaneously, improving overall treatment reliability.
2Ease of operation
If current treatments are used for NASH and ASH, then some symptomatic relief may be achieved, but hepatic fibrosis and inflammation are not effectively addressed
Solution Approach 1:
The oxygen-containing modified fatty acid derivatives are designed to perform multiple therapeutic functions simultaneously: reducing hepatic steatosis through fatty acid metabolism modulation, anti-inflammatory effects through cytokine suppression, and anti-fibrotic effects through stellate cell activation inhibition. This multi-functionality addresses all three key pathological features of NASH and ASH with a single agent.
3Duration of action of moving object
If fibrosis progression is allowed to continue in NASH patients, then disease progression occurs, but early intervention with existing treatments is insufficient to reverse established fibrosis
Solution Approach 1:
The patent enables preliminary action by using oxygen-containing modified fatty acid derivatives that can intervene early in the fibrotic process. These compounds prevent the activation and proliferation of hepatic stellate cells before extensive fibrosis develops, and can reverse early fibrotic changes through their anti-inflammatory and anti-proliferative effects on stellate cells.
Data Source
AI summary
The present disclosure provides a combination therapy for use in therapeutic and/or prophylactic treatment of non-alcoholic steatohepatitis (NASH) and/or alcoholic steatohepatitis (ASH), wherein the combination therapy comprises an unsaturated fatty acid with an oxygen incorporated in the β-position and an α-substituent and at least one additional active agent chosen from a glucagon-like peptide 1 receptor agonist, an acetyl-CoA carboxylase inhibitor, and a farnesoid X receptor agonist.