Modulating Enteric Neuron Ratios to Reverse Aging

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Solution Overview

Problem

The development of the human enteric nervous system (ENS) is poorly understood due to the lack of suitable model systems and limited access to primary tissue, leading to a lack of effective agents to reverse age-associated loss of ENS structure and function, which is critical for treating age-associated gastrointestinal dysmotility disorders.

Innovation Solution

Administering therapeutically effective amounts of agonists or antagonists of RET and MET receptor signaling, such as GDNF or HGF, to modulate the ratio of neural crest-derived enteric neurons (NENs) to mesodermal-lineage enteric neurons (MENs) to treat gastrointestinal disorders by promoting the growth or reduction of specific neuron populations.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Loss of information

If the development of human ENS is studied using traditional methods, then access to primary tissue is required, but this leads to limited understanding due to lack of suitable model systems

Engineering Contradiction:

Improveunderstanding of ENS developmentVSAvoidaccess to primary tissue

Core Design Contradiction:

Loss of informationVSEase of manufacture

Solution Approach 1:

The patent uses induced pluripotent stem cells (iPSCs) as a copy of primary ENS tissue. These iPSCs are generated from patient skin or blood cells and can be differentiated into enteric neuron populations that replicate the disease state without requiring direct access to the difficult-to-obtain primary ENS tissue, thus resolving the contradiction between understanding ENS development and accessing primary tissue

Inventive Principle:

Principle #26Copying

Solution Approach 2:

The patent introduces iPSCs as an intermediary system between the researcher and the primary ENS tissue. These stem cells serve as a accessible model that mediates the study of ENS development and disease, allowing researchers to investigate age-associated changes and neurodegeneration without needing direct access to the primary tissue, thereby improving understanding while maintaining ease of access

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If no therapeutic agents are used, then natural aging process occurs, but this leads to age-associated loss of ENS structure and function

Engineering Contradiction:

ImproveENS structure and functionVSAvoidage-associated degeneration

Core Design Contradiction:

ReliabilityVSLoss of time

Solution Approach 1:

The patent applies preliminary action by administering agonists of RET receptor signaling and/or antagonists of MET receptor signaling before significant age-associated neurodegeneration occurs. These agents act preventively to maintain or restore the population ratio of neural crest-derived to mesodermal-lineage enteric neurons, thereby preserving ENS structure and function rather than allowing natural age-related deterioration to proceed

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent utilizes parameter changes by modulating the population ratio of different enteric neuron lineages through pharmacological intervention. By changing the ratio of neural crest-derived to mesodermal-lineage neurons through RET/MET pathway modulation, the therapy reverses or prevents age-associated changes in ENS composition, thereby improving reliability of ENS function while countering the time-dependent degradation of neural structures

Inventive Principle:

Principle #35Parameter changes

3Reliability

If therapeutic agents are administered to reverse aging, then ENS structure and function improve, but this requires precise modulation of RET and MET signaling

Engineering Contradiction:

ImproveENS structure and functionVSAvoidsignaling modulation complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent simplifies the complex signaling modulation by focusing on changing key parameters - specifically the population ratio of neural crest-derived to mesodermal-lineage neurons. By using agonists of RET and antagonists of MET, the therapy achieves a favorable shift in this critical parameter, thereby improving ENS reliability without requiring complex multi-target intervention strategies

Inventive Principle:

Principle #35Parameter changes

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

This approach effectively modifies the population ratio of NENs to MENs, potentially reversing age-associated degeneration and improving gastrointestinal motility and function.

Implementation Method 1

agonist of RET receptor signaling

Methodology Applied

Scientific EffectReceptor signaling:

Implementation Method 2

antagonist of MET receiver signaling

Methodology Applied

Scientific EffectReceptor signaling:

Data Source

PatentUS20230346847A1Juvenile protective factors to arrest and reverse aging in the enteric nervous system

Publication Date: 2023.11.02 JOHNS HOPKINS UNIVERSITY

AI summary

Compositions and methods of use are provided in the treatment of age-associated gastrointestinal dysmotility disorders, along with other pathological manifestations of intestinal dysfunction and dysmotility disorders.