Diaminophenothiazine Inhibits Alpha-Synuclein Aggregation

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Solution Overview

Problem

Current treatments for Parkinson's disease primarily address symptoms rather than the underlying cause of α-synuclein aggregation, which is associated with neurodegeneration, and there is a lack of compounds specifically inhibiting or reversing this aggregation.

Innovation Solution

Diaminophenothiazine compounds are used to inhibit the aggregation of α-synuclein proteins, disrupting assembled forms and binding, thereby targeting the underlying cause of neurodegenerative diseases like Parkinson's disease.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current treatments for Parkinson's disease are used, then symptomatic relief is achieved, but the underlying cause of α-synuclein aggregation is not addressed

Engineering Contradiction:
Improvetherapeutic effectivenessVSAvoidα-synuclein aggregation
Core Design Contradiction:
ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent applies preliminary anti-action by using diaminophenothiazine compounds to prevent and disrupt α-synuclein aggregation before it can cause neurodegeneration. The compounds actively counteract the aggregation process through direct binding to α-synuclein monomers and oligomers, thereby addressing the root cause rather than merely treating symptoms

Inventive Principle:
Principle #9Preliminary anti-action

Solution Approach 2:

The patent converts the harmful aggregation process into a beneficial therapeutic outcome by using diaminophenothiazine compounds that specifically bind to and stabilize α-synuclein in non-aggregated forms. This transforms the pathological aggregation tendency into a controlled state where the protein remains functional without forming toxic aggregates

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

2Adaptability or versatility

If diaminophenothiazine compounds are used to inhibit α-synuclein aggregation, then the underlying cause is targeted, but compound specificity and concentration control are required

Engineering Contradiction:
Improvetherapeutic applicabilityVSAvoidcompound concentration control
Core Design Contradiction:
Adaptability or versatilityVSManufacturing precision

Solution Approach 1:

The patent applies parameter changes by optimizing the concentration ranges of diaminophenothiazine compounds to achieve maximum therapeutic effect while minimizing side effects. The invention specifies that these compounds effectively inhibit aggregation at controlled concentrations, transforming the challenge of concentration control into a defined therapeutic window

Inventive Principle:
Principle #35Parameter changes

Data Source

PatentEP2004155B1Inhibitors of protein aggregation
Publication Date: 2018.02.21 WISTA LAB LTD
  • EP2004155B1 patent drawingFigure 1~3
  • EP2004155B1 patent drawingFigure 4A~5D
  • EP2004155B1 patent drawingFigure 6A~7B

AI summary

The invention relates generally to the use of diaminophenothiazine compounds to inhibit or reverse the aggregation of synuclein, and for their use in the manufacture of medicaments for this purpose (e.g. for the treatment of Parkinson's Disease). Also provided are related methods of detecting or labelling of aggregated synuclein.