BGP15 Prevents NASH-Induced HCC Progression
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Solution Overview
Problem
Current treatments lack effectiveness in preventing hepatocellular carcinoma (HCC) induced by non-alcoholic steatohepatitis (NASH), a condition increasingly linked to obesity and fatty liver disease in developed countries, where the etiology remains unclear and existing uses of BGP15 do not address this specific prevention.
Innovation Solution
The compound O-(3-piperidino-2-hydroxy-1-propyl)-nicotinic amidoxime (BGP15) is used to prevent NASH-induced HCC, administered in various formulations for oral, parenteral, or transdermal delivery, potentially combined with other active agents, to target liver damage and inflammation in animal models mimicking human NASH features.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If BGP15 is used for treating diabetes and muscle atrophy as described in prior art, then those specific conditions are addressed, but NASH-induced HCC prevention is not achieved
Solution Approach 1:
The patent extends the utility of BGP15 from its previously known applications in diabetes and muscle atrophy treatment to a new function of preventing NASH-induced HCC. This demonstrates multi-functionality by showing that a single compound can address multiple distinct pathological conditions through its antioxidant and anti-inflammatory properties, thereby resolving the contradiction between versatility and targeted effectiveness
2Ease of operation
If existing treatments are used for NASH patients, then general liver support is provided, but prevention of HCC progression is not achieved
Solution Approach 1:
The patent introduces a novel therapeutic parameter - the use of BGP15 at specific dosages (e.g., 10-50 mg/kg body weight) to achieve HCC prevention. This changes the treatment parameter from general liver support to targeted HCC prevention through controlled administration of a specific compound, thereby improving reliability while maintaining ease of operation
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
BGP15 treatment significantly reduces liver fibrosis and ALT levels, demonstrating its potential in preventing the progression from NASH to HCC in animal models, suggesting a therapeutic avenue for this previously unaddressed condition.
Implementation Method 1
Nagy et al. (2010) describe how BGP15 prevents AIF mitochondria to nucleus translocation and mitochondrial depolarisation in liver cells
Implementation Method 2
WO2005123049 describes effect of BGP15 on mitochondrial genesis and its possible use in muscle regeneration
Implementation Method 3
Halmosi et a/. (2001) and Szabados et a/. (2000) show how BGP15 protects cardiac cells from reactive oxygen species (ROS) induced inactivation of mitochondria by virtue of its PARP-inhibitory action
Data Source
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AI summary
The present invention relates to methods of treating non-alcoholic steatohepatitis (NASH) and to methods of preventing NASH-induced hepatocellular carcinoma (HCC), such methods comprising administering O-(3-piperidino-2-hydroxy-1- propyl)-nicotinic amidoxime (BGP15), alone or in combination with a inhibitor of the interleukin-6 receptor transsignaling response, particularly gpl30Fc.