N-acetylglucosamine for Synucleinopathy Constipation and Aggregation

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Solution Overview

Problem

Current treatments are inadequate for effectively managing symptoms of synucleinopathies, particularly constipation and alpha-synuclein aggregation, which are prevalent in Parkinson's Disease and other related disorders, and impact both gastrointestinal and central nervous system functions.

Innovation Solution

Administration of N-acetylglucosamine or its analogues/derivatives to treat constipation and solubilize alpha-synuclein aggregates, thereby normalizing motor function in both the gut and central nervous system.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional treatments are used for synucleinopathies, then current standard care is provided, but effective management of constipation and alpha-synuclein aggregation is not achieved

Engineering Contradiction:
Improveeffectiveness of treatmentVSAvoidconstipation and alpha-synuclein aggregation
Core Design Contradiction:
ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent changes the chemical parameter by introducing N-acetylglucosamine, a glycosaminoglycan precursor, which modifies the biochemical environment to inhibit alpha-synuclein aggregation and improve gastrointestinal motilation. This chemical parameter change enables effective treatment of synucleinopathies where conventional treatments fail.

Inventive Principle:
Principle #35Parameter changes

2Reliability

If N-acetylglucosamine is administered, then constipation symptoms are reduced and alpha-synuclein aggregates decrease, but the mechanism of action is not fully understood

Engineering Contradiction:
Improvetherapeutic efficacyVSAvoidmechanism of action
Core Design Contradiction:
ReliabilityVSLoss of information

Solution Approach 1:

The patent identifies N-acetylglucosamine as an intermediary substance that mediates between the administration and the therapeutic effects. It serves as a precursor for glycosaminoglycan synthesis, which then exerts the protective effects against alpha-synuclein aggregation and improves gastrointestinal function, though the complete signaling pathway remains partially elucidated.

Inventive Principle:
Principle #24Intermediary (Mediator)

3Adaptability or versatility

If treatments are developed for synucleinopathies, then motor and gastrointestinal functions can be improved, but current options are insufficient

Engineering Contradiction:
Improvetreatment optionsVSAvoidtreatment effectiveness
Core Design Contradiction:
Adaptability or versatilityVSReliability

Solution Approach 1:

The patent develops a universal treatment approach using N-acetylglucosamine that addresses multiple symptoms of synucleinopathies simultaneously, including constipation, alpha-synuclein aggregation, and gastrointestinal motilation. This multi-functional approach provides versatile treatment options that conventional single-target therapies cannot achieve.

Inventive Principle:
Principle #6Universality (Multi-functionality)

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

N-acetylglucosamine effectively reduces constipation symptoms and decreases alpha-synuclein aggregates, improving bowel movements and motor function, as demonstrated in pilot studies with Parkinson's Disease patients.

Implementation Method 1

post-translational modification of GIcNAc specifically O-GIcNAcylation at threonine residue 72 (Thr72) may have a role in regulating protein folding and inhibiting Parkinson's Disease-associated a-synuclein (aSyn) aggregation

Methodology Applied
Scientific EffectO-GIcNAcylation: Chemical Bonding

Implementation Method 2

increasing the expression of sulphated glycosaminoglycan (GAG) which promotes proper gut functioning

Methodology Applied
Scientific EffectGlycosaminoglycan synthesis: Chemical Bonding

Data Source

PatentEP3737384B1Methods and compositions for preventing and treating conditions related to alpha-synuclein
Publication Date: 2023.10.25 PUREPHARM
  • EP3737384B1 patent drawingFigure 1

AI summary

Provided herein are methods of treating constipation in subjects in need thereof. The method includes administering a therapeutically effective dosage of N-acetylglucosamine. Subjects who may benefit from treatment include those having synucleinopathies, including Parkinson's Disease.