MEX3B Targeting for Steroid-Resistant Severe Asthma
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Solution Overview
Problem
Severe asthma is characterized by chronic inflammation and irreversible airway remodeling due to high levels of interleukin 17 (IL-17), chemokines CXCL1, CXCL2, and CXCL5, which recruit neutrophils, and is resistant to steroid treatment, with IL-6, IL-13, TNF, and G-CSF contributing to the disease progression.
Innovation Solution
A method for screening prophylactic or therapeutic agents using MEX3B gene or protein changes as an index, involving substances that decrease MEX3B expression or function to inhibit IL-6, IL-13, TNF, G-CSF, CXCL1, CXCL2, or CXCL5, using antisense oligonucleotides complementary to the MEX3B gene sequence.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If steroid agents are used to treat asthma, then allergic inflammation can be suppressed, but severe asthma showing Th17 cell excessive response and neutrophil infiltration becomes resistant to treatment
Solution Approach 1:
The invention extracts and targets the specific pathological mechanism of severe asthma by focusing on Th17 cell differentiation and IL-17 production. Instead of using general steroid agents that fail in severe asthma, the patent develops agents that specifically inhibit the IL-23/Th17 axis, thereby extracting the effective treatment pathway from the complex asthma pathogenesis and achieving treatment effectiveness where steroids fail.
Solution Approach 2:
The invention changes the treatment parameter from general anti-inflammatory steroids to specific cytokine pathway inhibition. By targeting the IL-23 receptor and blocking IL-23 signaling, the patent alters the therapeutic approach to specifically reduce Th17 cell differentiation and IL-17 production, thereby overcoming steroid resistance in severe asthma while maintaining treatment effectiveness.
2Object-affected harmful factors
If IL-17 levels are high in severe asthma, then neutrophil recruitment increases causing chronic inflammation, but reducing IL-17 requires specific targeted therapy rather than general anti-inflammatory treatment
Solution Approach 1:
The invention introduces an intermediary approach by targeting IL-23, which is upstream of IL-17 production in the cytokine signaling pathway. By blocking IL-23 receptor signaling, the patent indirectly reduces IL-17 levels and subsequent neutrophil recruitment, thereby simplifying the treatment approach while effectively addressing the harmful effects of high IL-17 without requiring direct IL-17 measurement or complex combination therapies.
3Object-affected harmful factors
If MEX3B gene expression is increased, then production of inflammatory cytokines (IL-6, IL-13, TNF, G-CSF, CXCL1, CXCL2, CXCL5) increases, but screening for therapeutic agents requires identifying substances that decrease MEX3B expression or function
Solution Approach 1:
The invention applies preliminary action by establishing MEX3B gene expression levels and inflammatory cytokine production as predictive markers before conducting agent screening. By pre-identifying substances that decrease MEX3B expression or function and measuring their impact on cytokine production upfront, the patent simplifies the screening process and reduces the difficulty of detecting effective therapeutic agents.
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 method allows for the identification of agents that can prevent or treat severe asthma and other diseases by targeting MEX3B, reducing the expression or function of IL-6, IL-13, TNF, G-CSF, CXCL1, CXCL2, and CXCL5, thereby mitigating chronic inflammation and airway remodeling.
Implementation Method 1
an antisense oligonucleotide which has a sequence complementary to an oligonucleotide comprising at least 10 contiguous nucleotides contained in the MEX3B gene
Implementation Method 2
a double-stranded RNA containing at least 20 contiguous nucleotides in a coding region or an untranslated region in the sequence of an RNA to be transcribed from the sequence of the MEX3B gene
Data Source
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AI summary
Provided are a method for screening agents for the prevention or treatment of diseases caused by interleukin 6, interleukin 13, TNF, G-CSF, CXCL1, CXCL2, or CXCL5 and an agent for the prevention or treatment of diseases caused by interleukin 6, interleukin 13, TNF, G-CSF, CXCL1, CXCL2, or CXCL5. A method for screening agents for the prevention or treatment of diseases caused by interleukin 6, interleukin 13, TNF, G-CSF, CXCL1, CXCL2, or CXCL5 having as the index at least one selected from the group consisting of changes in the expression of the MEX3B gene or MEX3B protein and changes in the function of the MEX3B protein.