PPAR Agonists Reduce Cytokine Secretion in Liver Failure
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Solution Overview
Problem
Current treatments for acute liver failure (ALF), decompensated cirrhosis, and acute on chronic liver failure (ACLF) are inadequate, leading to high mortality rates and a need for effective therapeutic options that can manage liver dysfunction and associated complications such as hepatic encephalopathy and kidney failure.
Innovation Solution
The use of PPAR agonists like lanifibranor, bezafibrate, fenofibrate, pemafibrate, seladelpar, saroglitazar, pioglitazone, rosiglitazone, and specific compounds of formula (I) or their pharmaceutically acceptable salts, which reduce cytokine production and improve liver function by administering them to patients with ALF, decompensated cirrhosis, and ACLF to prevent decompensation and organ failure.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current treatments are used for acute liver failure and decompensated cirrhosis, then standard care is provided, but mortality rates remain high and liver dysfunction is not effectively managed
Solution Approach 1:
The patent applies parameter changes by administering PPAR agonists to modify the physiological parameters of liver function. The PPAR agonists change the metabolic and inflammatory parameters in the liver, improving hepatic function and reducing mortality in acute liver failure and decompensated cirrhosis patients.
Solution Approach 2:
The patent uses PPAR agonists as intermediary substances that mediate between the harmful inflammatory response and liver tissue damage. These compounds act as mediators by binding to PPAR receptors and modulating gene expression to reduce inflammation and improve liver function.
2Reliability
If PPAR agonists are administered to reduce cytokine production, then hepatic function improves and liver failure is mitigated, but the mechanism involves complex anti-inflammatory pathways
Solution Approach 1:
The patent applies preliminary action by administering PPAR agonists before severe liver failure develops or at the early stages of acute liver failure and decompensated cirrhosis. This preliminary intervention prevents the progression to end-stage liver failure by proactively reducing inflammation and improving hepatic function.
Solution Approach 2:
The patent demonstrates universality by using PPAR agonists that can treat multiple conditions (acute liver failure, decompensated cirrhosis, ACLF) through a single mechanism of action. The PPAR agonists perform multiple functions including anti-inflammatory effects, improvement of hepatic function, and reduction of mortality across different liver disease stages.
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
These PPAR agonists effectively decrease TNFα and MCP1 secretion, reduce cytokine production, and improve hepatic function, thereby mitigating liver failure and associated complications, as demonstrated by their ability to inhibit macrophage activation and reduce circulating cytokine levels in preclinical models.
Implementation Method 1
PPAR agonists like lanifibranor, bezafibrate, fenofibrate, pemafibrate, seladelpar, saroglitazar, pioglitazone, rosiglitazone
Data Source
AI summary
The invention relates to compounds for use in the treatment of liver failure.