Epoxy-Fatty Acid Therapy for Immune-Related Neurodevelopmental Deficits
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Maternal immune activation during pregnancy increases the risk of neurodevelopmental disorders such as schizophrenia and autism spectrum disorder in offspring, with the precise mechanisms underlying these disorders remaining unclear, and existing animal models do not fully replicate the immune responses induced by infectious pathogens.
Innovation Solution
Administering agents that increase the levels of epoxy-fatty acids, such as inhibitors of soluble epoxide hydrolase (sEH), to prevent, reduce, or ameliorate symptoms associated with neurodevelopmental disorders by increasing the levels of epoxy-fatty acids, thereby mitigating the effects of maternal immune activation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If immune-activating agents such as poly(I:C) are used to model maternal immune activation, then neurobiological pathways between MIA and neurodevelopmental disorders can be studied, but the full spectrum of immune responses normally induced by infectious pathogens is not reproduced
Solution Approach 1:
The patent introduces soluble epoxide hydrolase (sEH) as an intermediary target to bridge the gap between simplified poly(I:C) models and complex infectious pathogen responses. By inhibiting sEH, the model reproduces key immune response features including elevated pro-inflammatory cytokines and altered epoxy-fatty acid levels that are normally seen in maternal infections, without requiring complex pathogen exposure
2Reliability
If soluble epoxide hydrolase inhibitors are administered to increase epoxy-fatty acid levels, then cognitive deficits and social interaction deficits in offspring are prevented or reduced, but the mechanism by which EpoFAs mitigate MIA effects remains to be fully elucidated
Solution Approach 1:
The patent establishes a feedback loop where sEH inhibition leads to elevated epoxy-fatty acid levels, which then exert therapeutic effects on neurodevelopmental outcomes. The feedback mechanism involves monitoring behavioral phenotypes and neurobiological markers to confirm that the therapeutic effect is mediated through the intended pathway, while the patent acknowledges that further research is needed to fully map the mechanistic details
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 administration of epoxy-fatty acid-increasing agents, including sEH inhibitors, effectively prevents or reduces cognitive deficits and social interaction deficits in offspring exposed to maternal immune activation, suggesting a promising therapeutic target for neurodevelopmental disorders.
Implementation Method 1
these mediators are broken down into their corresponding diols by soluble epoxide hydrolase (sEH), and inhibition of sEH enhances the beneficial effects of EpFAs
Data Source
AI summary
Provided herein are methods of preventing, reducing, ameliorating, mitigating, inhibiting, treating and/or reversing a neurodevelopmental disorder related to prenatal maternal immune activation in an individual in need thereof comprising administering to said individual an agent that increases the level of epoxy-fatty acids wherein said individual experienced maternal immune activation one or more times during gestation. Also provided herein are methods of preventing, reducing, ameliorating, mitigating, inhibiting treating and/or reversing schizophrenia or autism spectrum disorder an individual comprising administering to said individual an agent that increases the level of epoxy-fatty acids.