Cyclic Peptides Binding Amyloid-Beta Oligomers

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Solution Overview

Problem

Current treatments for Alzheimer's disease do not effectively prevent the formation or proliferation of toxic amyloid beta oligomers, and existing diagnostic methods cannot detect the disease before symptoms appear, as they rely on neuro-psychological tests and cannot identify small, freely diffusible oligomers or fibrils in the brain.

Innovation Solution

Development of peptides with modified C-termini, such as amidated or cyclized forms, that bind specifically and with high affinity to amyloid beta species, including oligomers, to prevent their formation, eliminate them, or convert them into non-toxic forms, and serve as probes for early diagnosis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If conventional medications are used to treat Alzheimer's disease, then some symptoms are alleviated, but the progression of the disease cannot be slowed or cured

Engineering Contradiction:
Improvesymptom reliefVSAvoiddisease progression control
Core Design Contradiction:
Ease of operationVSReliability

Solution Approach 1:

The patent uses cyclic peptides that structurally mimic and bind to amyloid-beta oligomers, effectively copying the target structure to create high-affinity binders. These peptides serve as molecular copies that neutralize the toxic oligomers without triggering immune responses, thereby addressing the limitation of conventional medications that only alleviate symptoms rather than targeting the underlying cause.

Inventive Principle:
Principle #26Copying

2Quantity of substance

If substances are used to reduce A-beta monomer concentration, then monomer levels decrease, but this is insufficient to prevent oligomer formation in clinical trials

Engineering Contradiction:
ImproveA-beta monomer concentrationVSAvoidoligomer prevention efficacy
Core Design Contradiction:
Quantity of substanceVSReliability

Solution Approach 1:

The patent converts the harmful effect of A-beta oligomers into a beneficial diagnostic and therapeutic opportunity by designing cyclic peptides that specifically bind to and neutralize these oligomers. The same oligomeric structures that cause disease toxicity become the target for high-affinity binding, allowing both therapeutic neutralization and diagnostic detection through the cyclic peptide probes.

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

3Ease of operation

If diagnostic methods rely on neuro-psychological tests, then symptoms can be assessed, but the disease cannot be detected before symptom onset

Engineering Contradiction:
Improvediagnostic simplicityVSAvoidearly disease detection capability
Core Design Contradiction:
Ease of operationVSMeasurement precision

Solution Approach 1:

The patent employs cyclic peptides that can be labeled with fluorescent or radiolabeled tags, enabling visual detection of A-beta oligomers through imaging techniques. This allows the 'color change' or signal generation principle to be applied, where the binding of labeled cyclic peptides to oligomers produces detectable signals that indicate early disease presence before clinical symptoms manifest.

Inventive Principle:
Principle #32Color changes

4Device complexity

If small, freely diffusible A-beta oligomers are the main cause of AD progression, then they are difficult to detect and target, but they must be neutralized to influence disease course

Engineering Contradiction:
Improveoligomer detection difficultyVSAvoiddisease course influence
Core Design Contradiction:
Device complexityVSReliability

Solution Approach 1:

The patent applies local quality by designing cyclic peptides with specific structural features (cyclization, amino acid composition) that confer high local affinity for A-beta oligomers. This localized optimization of binding properties at the molecular level enables the peptides to effectively target and neutralize the diffuse oligomers throughout the brain, overcoming the difficulty of targeting these mobile, small structures.

Inventive Principle:
Principle #3Local quality

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

These peptides demonstrate enhanced binding affinity and specificity, effectively preventing the formation and proliferation of toxic amyloid beta species, and can be used for both therapeutic and diagnostic purposes, including early detection of Alzheimer's disease by binding to small concentrations of oligomers.

Implementation Method 1

containing at least one amino acid sequence which binds to amyloid-beta species

Methodology Applied
Scientific EffectMolecular binding:

Data Source

PatentEP3747454B9Amyloid-beta binding peptides and these peptides for use in the therapy and diagnosis of alzheimer's dementia
Publication Date: 2023.10.04 PRIAVOID GMBH
  • EP3747454B9 patent drawingFigure 1
  • EP3747454B9 patent drawingFigure 2
  • EP3747454B9 patent drawingFigure 3

AI summary

The invention relates to amyloid-beta binding peptides and their use for the therapy and diagnosis of Alzheimer's dementia.