Bile Acid Derivatives for FXR-Mediated Cognitive Protection
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Solution Overview
Problem
There is a need for effective treatments to ameliorate, mitigate, or prevent cognitive impairment and neurodegenerative diseases such as Parkinson's disease dementia, as current therapies are inadequate and there is a significant unmet clinical need for alternative cognitive enhancers.
Innovation Solution
Administration of bile acid derivatives, specifically compounds of formula (I) or their pharmaceutically acceptable salts, esters, solvates, or amino acid conjugates, to subjects to ameliorate, mitigate, or prevent cognitive impairment and neurodegenerative diseases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current therapies are used for cognitive impairment, then treatment is provided, but treatment effectiveness is inadequate
Solution Approach 1:
The patent modifies the chemical structure of bile acids by changing parameters such as adding alkyl groups at specific positions (e.g., C6, C7, C12, C13) and modifying side chains. These structural parameter changes create derivatives with enhanced FXR agonist activity and improved cognitive protective effects compared to natural bile acids.
Solution Approach 2:
The patent creates composite molecular structures by combining the core bile acid skeleton with various functional groups and side chains (e.g., hydroxy groups, carboxylic acid groups, alkyl substituents). These composite structures achieve synergistic effects that improve both cognitive protection and metabolic regulation.
2Ease of operation
If no cognitive treatments are available for Parkinson's disease, then patient care is maintained, but quality of life deteriorates
Solution Approach 1:
The patent uses bile acid derivatives as intermediary substances that activate the FXR receptor in the brain, serving as a mediator between dietary bile acids and cognitive protection. These derivatives bridge the gap between available metabolic substrates and the need for cognitive enhancement in Parkinson's disease patients.
3Reliability
If bile acid derivatives are administered, then cognitive impairment is ameliorated, but compound complexity increases
Solution Approach 1:
The patent introduces functional groups and substituents at specific local positions of the bile acid molecule (e.g., C6, C7, C12, C13 positions) rather than uniformly modifying the entire structure. This localized modification approach maintains the core bile acid framework while adding specific cognitive-protective properties at key sites.
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 compounds effectively ameliorate, mitigate, or prevent cognitive impairment and associated cellular senescence, potentially slowing the progression of neurodegenerative diseases like Parkinson's disease dementia.
Implementation Method 1
Obeticholic acid (OCA) is a modified bile acid and famesoid X receiver (FXR) agonist. Based on preclinical data, OCA can reverse cognitive dysfunction in cholestasis (e.g., PBC) when given early in the disease course
Data Source
AI summary
The disclosure relates to methods of using bile acid derivatives for the treatment and/or prevention of cognitive disorders, diseases, or conditions.