Somatic Mutation Detection for NAFLD Diagnosis
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Solution Overview
Problem
Current methods lack reliable diagnostic and prognostic tests for non-alcoholic fatty liver disease (NAFLD) and alcohol-related fatty liver disease (ARLD), and there are no specific treatments available for these conditions, making early detection and management challenging.
Innovation Solution
The method involves detecting somatic mutations in liver cells, particularly in the FOXO1, GPAM, CIDEB, ACVR2A, ALB, and TNRC6B genes, which confer a selective advantage and are used as markers for diagnosing and prognosing NAFLD/ARLD, and therapeutic agents that inhibit or modulate these proteins to treat the diseases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If invasive liver biopsies are used to definitively diagnose NAFLD, then diagnostic accuracy is improved, but patient harm and procedural risk increase
Solution Approach 1:
The patent uses circulating tumor DNA (ctDNA) as an intermediary biomarker to indirectly detect liver disease presence and progression without direct tissue sampling. The ctDNA serves as a mediator that carries genetic information from liver lesions to circulating blood, enabling non-invasive diagnosis while maintaining diagnostic accuracy
Solution Approach 2:
The patent replaces the mechanical invasive procedure of liver biopsy with a non-invasive blood test that detects molecular biomarkers. This substitution eliminates the need for physical tissue sampling while providing equivalent diagnostic information through genetic analysis of circulating DNA
2Loss of information
If inherited genetic variations are detected to assess NAFLD risk, then genetic predisposition is identified, but reliable diagnosis of actual liver disease is limited
Solution Approach 1:
The patent shifts the diagnostic parameter from germline genetic variations (inherited risk factors) to somatic mutations (acquired changes in liver cells). This parameter change enables detection of actual disease presence and progression rather than just genetic predisposition, significantly improving diagnostic reliability
Solution Approach 2:
The patent performs preliminary detection of somatic mutations in circulating DNA to identify liver disease before clinical symptoms manifest. This early detection capability allows for proactive monitoring and intervention, improving both diagnostic timing and reliability
3Adaptability or versatility
If no specific diagnostic tests are available for NAFLD, then treatment options remain limited, but early detection and intervention are hindered
Solution Approach 1:
The patent implements preliminary detection of liver disease through ctDNA analysis before significant liver damage occurs. This early identification enables timely intervention and treatment planning, preventing disease progression to more severe stages
Solution Approach 2:
The patent establishes a feedback mechanism by monitoring changes in ctDNA levels and mutation profiles over time. This longitudinal tracking provides dynamic information about disease progression or response to treatment, enabling adaptive therapeutic decisions and personalized medicine approaches
Data Source
AI summary
The present invention concerns methods of diagnosing and/or prognostication of non-alcoholic fatty liver disease (NAFLD) or alcohol-related fatty liver disease (ARLD) in a subject, wherein said methods comprise detecting somatic mutations in DNA, RNA and/or protein that confer a selective advantage on one or more liver cells of the subject. The present invention also provides methods for identifying subjects suffering from NAFLD or ARLD who would benefit from treatment with a therapeutic agent and/or identifying subjects suffering from NAFLD or ARLD who would benefit from increased disease monitoring. The present invention also provides therapeutic agents that find utility in the treatment of NAFLD or ARLD.