MAPK Pathway Inhibition for vEDS Vascular Dissection Prevention

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Solution Overview

Problem

Current treatments for vascular Ehlers-Danlos Syndrome (vEDS) and related connective tissue disorders are inadequate, as they fail to effectively manage the premature and life-threatening vascular dissections and organ ruptures associated with the condition, primarily due to the lack of targeted therapeutic strategies.

Innovation Solution

Administration of agents that inhibit the activity or expression of extracellular signal-regulated kinase (ERK) or protein kinase C (PKC), such as small molecules or nucleic acid molecules, to reduce the severity of vasculopathies by targeting the mitogen-activated protein kinase (MAPK) pathway, thereby preventing vascular dissections and organ ruptures.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional treatments are used for vEDS, then general symptom management is provided, but life-threatening vascular dissections and organ ruptures cannot be effectively prevented

Engineering Contradiction:

Improveprevention of vascular dissection and organ ruptureVSAvoidlack of targeted therapeutic strategy

Core Design Contradiction:

ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent changes the therapeutic parameter from general symptom management to targeted inhibition of specific signaling pathways (TGF-β, MAPK, RhoA/ROCK). This is achieved by administering agents that specifically inhibit these pathways, transforming the treatment approach from non-specific to mechanism-based therapy that addresses the root molecular pathology of vEDS

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent introduces molecular intermediaries (small molecule inhibitors, antibodies, nucleic acid molecules) that mediate the inhibition of pathological signaling pathways. These intermediaries specifically target and block the abnormal molecular signaling in vEDS, serving as precise therapeutic mediators between the administered drug and the disease mechanism

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If targeted pathway inhibition is implemented, then prevention of vascular complications is achieved, but treatment complexity increases

Engineering Contradiction:

Improvesurvival rate improvementVSAvoidtreatment mechanism complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent extracts and targets specific pathological signaling pathways (TGF-β, MAPK, RhoA/ROCK) from the complex cellular signaling network. By isolating and inhibiting only the relevant pathological pathways rather than attempting to modulate the entire signaling system, the treatment achieves high reliability with manageable complexity

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent segments the complex disease mechanism into distinct targetable pathways and addresses each separately with specific inhibitors. This segmentation allows for modular treatment approaches where different pathway inhibitors can be selected or combined based on the specific patient needs and disease manifestation

Inventive Principle:

Principle #1Segmentation

Data Source

PatentUS20240408091A1Compositions and methods for treating vascular ehlers danlos syndrome and associated disorders

Publication Date: 2024.12.12 JOHNS HOPKINS UNIVERSITY

AI summary

The present invention relates to compositions and methods for treating vascular Ehlers Danlos Syndrome and associated connective tissue disorders.