Phosphorylated Alpha-Synuclein Detection for Ante-Mortem Parkinson’s Diagnosis

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Solution Overview

Problem

Current diagnostic methods for Parkinson's disease are inadequate for accurate ante-mortem diagnosis, hindering the development of therapeutic agents and relying on post-mortem confirmation of alpha-synuclein aggregation and dopaminergic neuron loss.

Innovation Solution

A method involving contacting a biological sample with a primary antibody capable of binding phosphorylated alpha-synuclein to detect its localization within nerve features, using histochemical analysis or kits comprising specific antibodies to generate detectable signals, enabling ante-mortem diagnosis of Parkinson's disease.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If post-mortem brain tissue analysis is used to confirm Parkinson's disease, then diagnostic accuracy is improved, but the ability to provide ante-mortem diagnosis and enable therapeutic interventions is lost

Engineering Contradiction:
Improvediagnostic accuracyVSAvoidtime for therapeutic intervention
Core Design Contradiction:
Measurement precisionVSLoss of time

Solution Approach 1:

The patent extracts the diagnostic marker (phosphorylated alpha-synuclein) from its traditional location (brain tissue) and detects it in accessible peripheral tissues such as skin, colon, or submandibular gland. This allows the definitive diagnostic test to be performed ante-mortem on living subjects, enabling therapeutic interventions while maintaining diagnostic accuracy through detection of the same pathological marker.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent uses peripheral tissues as intermediaries to reflect the pathological state of the brain. By detecting phosphorylated alpha-synuclein in these accessible tissues, the test serves as a mediator that provides indirect but accurate information about brain pathology, enabling ante-mortem diagnosis without requiring brain tissue access.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Loss of time

If clinical examination and DaTscan imaging are used for Parkinson's disease diagnosis, then ante-mortem assessment is enabled, but diagnostic accuracy and definitiveness are reduced

Engineering Contradiction:
Improvetime for diagnosisVSAvoiddiagnostic accuracy
Core Design Contradiction:
Loss of timeVSMeasurement precision

Solution Approach 1:

The patent replaces the indirect functional assessment methods (clinical examination observing motor symptoms, DaTscan imaging measuring dopamine transporter function) with direct detection of the pathological hallmark (phosphorylated alpha-synuclein aggregation). This substitution provides definitive diagnostic accuracy while maintaining ante-mortem capability, as the same aggregation process occurs in both brain and peripheral tissues.

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

3Measurement precision

If post-mortem brain tissue analysis is required to detect aggregated alpha-synuclein, then definitive diagnosis is achieved, but the complexity and invasiveness of sample acquisition increases

Engineering Contradiction:
Improvediagnostic accuracyVSAvoidsample acquisition complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent extracts the diagnostic target (aggregated alpha-synuclein) from the inaccessible brain tissue and relocates the detection to accessible peripheral tissues. This extraction eliminates the need for complex or invasive sample acquisition procedures while maintaining detection of the same pathological marker, thereby reducing sample acquisition complexity without sacrificing diagnostic accuracy.

Inventive Principle:
Principle #2Taking out (Extraction)

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

Enables definitive and accurate identification of Parkinson's disease in living subjects, facilitating therapeutic interventions.

Implementation Method 1

contacting a biological sample comprising at least one nerve feature from the subject with a primary antibody capable of binding phosphorylated alpha-synuclein

Methodology Applied
Scientific EffectAntigen-antibody binding:

Data Source

PatentUS12372537B2Determination of Parkinson's disease
Publication Date: 2025.07.29 F HOFFMANN LA ROCHE INC
  • US12372537B2 patent drawing
  • US12372537B2 patent drawing
  • US12372537B2 patent drawing

AI summary

Methods and compositions for accurate identification of Parkinson's disease are disclosed. More particularly, the disclosure is directed to the determination of Parkinson's disease in ante-mortem tissue samples.