E-cadherin Up-regulators for Intestinal Barrier Stabilization

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Solution Overview

Problem

Current treatments for inflammatory bowel diseases, such as Crohn's disease, are inadequate due to high costs, inefficiencies, and side effects, and fail to effectively manage the pro-inflammatory local environment, leading to recurrent flare-ups and significant tissue damage.

Innovation Solution

The use of E-cadherin up-regulators or agonists, specifically compounds like ML327 and those described in Formulas I and II, to up-regulate E-cadherin expression, which stabilizes the intestinal epithelial barrier, reduces permeability, and promotes wound healing, thereby addressing inflammation and tissue damage.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Object-affected harmful factors

If current treatment options (oral medications, biological reagents) are used to combat hyperactive inflammatory response, then inflammation is suppressed, but treatment efficiency is low, costs are high, and side effects including cancer risk occur

Engineering Contradiction:

Improveinflammatory responseVSAvoidtreatment effectiveness

Core Design Contradiction:

Object-affected harmful factorsVSReliability

Solution Approach 1:

The patent converts the harmful effect of chronic inflammation into a beneficial therapeutic target by using the body's own inflammatory signaling pathways (NF-κB, AP-1, STAT3) to induce E-cadherin expression. Instead of merely suppressing inflammation with immunosuppressants, the invention harnesses inflammatory cytokines to upregulate E-cadherin, which then strengthens the epithelial barrier and reduces intestinal permeability, thereby treating IBD through a mechanism that utilizes rather than对抗 the inflammatory response

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

Solution Approach 2:

The patent changes the molecular expression parameter of E-cadherin in the intestinal epithelium by administering compounds that specifically upregulate its expression. This parameter change (increased E-cadherin levels) directly strengthens cell-cell adhesion and barrier function, providing a more effective and safer treatment alternative to conventional immunosuppressive therapies

Inventive Principle:

Principle #35Parameter changes

2Adaptability or versatility

If inflammatory response is allowed to proceed unchecked, then immune system combats foreign insults, but severe tissue damage and death occur

Engineering Contradiction:

Improveimmune responseVSAvoidtissue integrity

Core Design Contradiction:

Adaptability or versatilityVSStrength

Solution Approach 1:

The patent introduces E-cadherin as an intermediary molecule between the immune response and tissue integrity. E-cadherin acts as a mediator that translates inflammatory signaling into protective barrier reinforcement, allowing the immune system to combat pathogens while simultaneously strengthening the epithelial barrier to prevent tissue damage and maintain structural integrity during the inflammatory response

Inventive Principle:

Principle #24Intermediary (Mediator)

Data Source

PatentUS20220008402A1Increased e-cadherin expression or activity for the treatment of inflammatory diseases

Publication Date: 2022.01.13 THE CLEVELAND CLINIC FOUND

AI summary

Provided herein are methods and systems employing agents that up-regulate E-cadherin, or E-cadherin agonists, for the treatment of inflammatory diseases, such as inflammatory bowel diseases (e.g., Crohn's disease). In certain embodiments, the agent employed is ML327, E-cadherin Up-regulator (ECU), or a compound of Formula I or II.