Gene Expression Profiling for IBD Treatment Responsiveness
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Solution Overview
Problem
Existing treatments with anti-TNFalpha and anti-α4β7 agents for inflammatory bowel diseases like ulcerative colitis and Crohn's disease are ineffective for a significant proportion of patients, leading to uncertainty and potential side effects, necessitating a method to predict treatment responsiveness.
Innovation Solution
A method involving the analysis of gene expression profiles, particularly IL7R, STAT5A, JAK1, JAK3, and other genes, in colonic mucosal samples to determine the likelihood of responsiveness to anti-TNFalpha and anti-α4β7 therapies.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If anti-TNFalpha agents are administered to treat inflammatory bowel disease, then inflammation is reduced in responsive patients, but treatment is ineffective and causes side effects in non-responsive patients
Solution Approach 1:
The patent applies preliminary action by performing gene expression analysis on colonic mucosal samples before administering anti-TNFalpha therapy. The method determines the expression profile of specific genes (IL7R, STAT5A, JAK1, JAK3, and others) to predict treatment responsiveness in advance, allowing clinicians to identify non-responsive patients before they receive ineffective treatment and potential side effects.
2Measurement precision
If treatment responsiveness is assessed through clinical trial response, then treatment efficacy is confirmed, but time is lost administering ineffective treatment during the trial period
Solution Approach 1:
The patent performs gene expression profiling as a preliminary action before initiating treatment trials. By analyzing the expression levels of specific genes in colonic mucosal samples, the method predicts treatment responsiveness in advance, eliminating the need to wait for clinical trial outcomes to determine whether a patient will respond to anti-TNFalpha therapy.
3Measurement precision
If gene expression profiling of multiple genes is performed, then prediction accuracy of treatment responsiveness is improved, but test complexity increases
Solution Approach 1:
The patent applies segmentation by focusing on a specific, limited set of genes (IL7R, STAT5A, JAK1, JAK3, and at least one additional gene from a defined group) rather than analyzing the entire genome. This segmented approach to gene expression profiling maintains high prediction accuracy while reducing test complexity compared to comprehensive genomic analysis.
Data Source
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AI summary
The invention relates to the identification of biomarkers of the response status of a patient for a treatment with anti-TNFalpha agents,for treatment with anti-α4β7 agents or with both anti-TNFalpha agent and anti-α4β7agents and to their use in assessing such status, in particular for assessing nonresponsive status for a treatment with anti-TNFalpha agents or respectively with anti-α4β7 agent in human patients suffering from inflammatory condition or disease, in particular Inflammatory Bowel Disease (IBD), in particular Ulcerative Colitis or Crohn's disease. The invention describes a method of in vitro assessing whether a treatment with anti- TNFalpha agent or with anti-α4β7 agent may be useful in a human patient suffering from inflammatory condition or disease, in particular when said condition or disease is a chronic and/or relapsing one, particularly a gastrointestinal, more particularly intestinal, inflammatory condition or disease which is eligible for treatment with anti-TNFalpha agent or respectively with anti-α4β7 agent. In a specific embodiment the method is suitable to assess whether such patient would be non- responsive to treatment with such anti-TNFalpha agent or respectively with anti-α4β7 agent and comprising determining a molecular signature in a biological sample previously obtained from said human patient.