Alpha-Synuclein Toxicity Modulators via Gene Expression Control

Resolve Bottlenecks,
Find Innovative Solutions
Generate Solutions

Solution Overview

Problem

Current treatments lack effective methods to inhibit alpha-synuclein mediated toxicity, which contributes to neurodegenerative diseases such as Parkinson's disease, as existing approaches fail to adequately prevent aggregation or promote fibril disaggregation.

Innovation Solution

Identification of specific genes that modulate alpha-synuclein mediated cellular toxicity, allowing for the development of compounds that inhibit expression or activity of target proteins, thereby reducing toxicity and treating or preventing synucleinopathies.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current treatment approaches are used, then existing therapies are available, but they fail to adequately prevent aggregation or promote fibril disaggregation of alpha-synuclein

Engineering Contradiction:
Improveeffectiveness of treatmentVSAvoidalpha-synuclein aggregation
Core Design Contradiction:
ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent identifies genes that are naturally overexpressed in response to alpha-synuclein toxicity (harmful condition) and converts this harmful response into a beneficial therapeutic strategy. By targeting these same genes pharmacologically, the treatment harnesses the cell's natural protective response to develop effective therapies that prevent aggregation and promote disaggregation of alpha-synuclein.

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

Solution Approach 2:

The patent employs a screening approach that identifies genes modulating alpha-synuclein toxicity before disease progression occurs. By discovering and targeting these genes in advance, the treatment prevents the formation of toxic aggregates rather than merely responding to established pathology, thereby improving treatment reliability.

Inventive Principle:
Principle #10Preliminary action

2Stability of the object's composition

If alpha-synuclein aggregation is allowed to proceed, then Lewy body formation occurs, but this leads to neuronal degeneration and Parkinson's disease pathology

Engineering Contradiction:
ImproveLewy body structureVSAvoidneuronal toxicity
Core Design Contradiction:
Stability of the object's compositionVSObject-affected harmful factors

Solution Approach 1:

The patent applies preliminary anti-action by identifying genes that oppose alpha-synuclein aggregation before Lewy bodies form. The therapeutic approach uses pharmacological modulation of these genes to prevent the aggregation process itself, thereby eliminating the harmful effect on neurons while avoiding the need to dismantle formed Lewy bodies.

Inventive Principle:
Principle #9Preliminary anti-action

Solution Approach 2:

The patent introduces gene modulators as intermediary substances that mediate between alpha-synuclein and the cellular response. These modulators target specific genes involved in the aggregation process, acting as intermediaries that prevent toxic interactions between alpha-synuclein and neuronal components, thereby protecting neurons without directly altering Lewy body structure.

Inventive Principle:
Principle #24Intermediary (Mediator)

Data Source

PatentUS9909160B2Modulators of alpha-synuclein toxicity
Publication Date: 2018.03.06 WHITEHEAD INST FOR BIOMEDICAL RES

AI summary

Disclosed are genes that, when overexpressed in cells expressing alpha-synuclein, either suppress or enhance alpha-synuclein mediated cellular toxicity. Compounds that modulate expression of these genes or activity of the encoded proteins can be used to inhibit alpha-synuclein mediated toxicity and used to treat or prevent synucleinopathies such as Parkinson's disease. Also disclosed are methods of identifying inhibitors of alpha-synuclein mediated toxicity.