Ala673Val Mutation Peptides for Alzheimer's Diagnosis

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Solution Overview

Problem

Current methods for diagnosing and managing Alzheimer's disease, particularly those related to anomalous β-amyloid deposition, are inadequate, and the underlying mechanisms of amyloid cascade hypothesis are not fully understood, leading to challenges in prevention and care.

Innovation Solution

A new punctiform mutation in the APP gene (Ala673Val) is identified, which influences Aβ production and aggregation, and synthetic peptides based on this mutation are used to inhibit amyloidogenesis, offering potential therapeutic strategies and diagnostic tools.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If current diagnostic methods are used for Alzheimer's disease, then diagnosis can be performed, but the precision and reliability are inadequate due to insufficient understanding of amyloid cascade mechanisms

Engineering Contradiction:
Improvediagnostic precisionVSAvoiddiagnostic reliability
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent replaces conventional diagnostic methods with a genetic testing approach that detects specific mutations (Swedish mutation at positions 670-671 and Florida mutation at position 692) in the APP gene. This molecular-level detection method substitutes traditional clinical assessment and imaging techniques, providing direct evidence of amyloidogenic risk based on the amyloid cascade hypothesis.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent uses polymerase chain reaction (PCR) technology to amplify and detect specific mutant APP gene sequences. This molecular copying approach allows for sensitive detection of pathogenic mutations in clinical samples, enabling precise identification of individuals at high risk for early-onset Alzheimer's disease.

Inventive Principle:
Principle #26Copying

2Reliability

If prevention and care strategies are developed without full understanding of amyloid cascade mechanisms, then some interventions can be implemented, but their effectiveness is limited

Engineering Contradiction:
Improvetherapeutic effectivenessVSAvoidmechanism understanding
Core Design Contradiction:
ReliabilityVSLoss of information

Solution Approach 1:

The patent enables preliminary identification of individuals carrying pathogenic APP mutations before clinical symptoms manifest. By detecting the Swedish and Florida mutations through genetic testing, the system allows for early intervention strategies to be implemented during the pre-symptomatic phase, potentially preventing or delaying disease onset before irreversible neurodegeneration occurs.

Inventive Principle:
Principle #10Preliminary action

3Reliability

If synthetic peptides based on Ala673Val mutation are used to inhibit amyloidogenesis, then therapeutic protection may be achieved, but the complexity of peptide synthesis and administration increases

Engineering Contradiction:
Improveprotective effectVSAvoidtherapeutic system complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent employs synthetic peptides that replicate the protective effect of the Ala673Val mutation. These peptides are designed to mimic the natural inhibitory mechanism by blocking amyloidogenic processing of APP, thereby preventing Aβ aggregation without requiring genetic modification of the patient.

Inventive Principle:
Principle #26Copying

Data Source

PatentEP2220251B1Method for the diagnosis of pathologies characterised by the anomalous deposition of amyloid in organs and tissues by detecting a mutation at position 673 in APP770, and vector and peptide for use in the therapy of said pathologies
Publication Date: 2016.08.03 FOND I R C C S INST NEUROLOGICO CARLO BESTA
  • EP2220251B1 patent drawingFigure 1
  • EP2220251B1 patent drawingFigure 2
  • EP2220251B1 patent drawingFigure 3

AI summary

The patent refers to a screening method carried out on biological material isolated from human and/or animal organisms for determining the risk of human and/or animal pathologies expressing an anomalous deposition of β-amyloid and/or amyloid- like substance in human and/or animal organs and tissues, based on the investigation of the punctiform mutation Ala>Val in position 2 of the β-protein (corresponding to the Ala673Val mutation precursor of the β-protein containing 770 amino acids) in homozygosis or in heterozygosis. The patent provides for the possibility of: (1) creating unicellular or multicellular transgenic organisms expressing the Ala673Val mutation; (2) synthesising or producing peptides with such mutation and/or their derivatives and/or nucleic acids containing the same mutation; (3) using such products for studying the pathogenesis of the pathologies characterised by anomalous deposition of β-amyloid and/or amyloid substance and for the prevention, diagnosis and care of such diseases.