Phosphorylated Alpha-Synuclein Detection for Ante-Mortem Parkinson's Diagnosis
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Solution Overview
Problem
Current diagnostic methods for Parkinson's disease (PD) are inadequate for accurate ante-mortem identification, hindering the development of therapeutic agents, as definitive diagnosis requires post-mortem analysis of aggregated alpha-synuclein in neurons.
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, combined with histochemical analysis, to diagnose PD in living subjects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If post-mortem analysis is used to definitively diagnose PD, then diagnostic accuracy is improved, but the ability to provide ante-mortem diagnosis and enable timely therapeutic intervention deteriorates
Solution Approach 1:
The patent applies preliminary action by performing diagnostic testing on accessible tissues (skin, colon, submandibular gland) before death occurs. The method detects phosphorylated alpha-synuclein in nerve fibers of these tissues ante-mortem, allowing diagnosis to be made in advance rather than waiting for post-mortem brain analysis. This enables timely therapeutic intervention while maintaining diagnostic accuracy through specific detection of pathologic phosphorylated alpha-synuclein aggregates.
2Loss of time
If clinical examination and DaTscan imaging are used for PD diagnosis, then the diagnosis can be made ante-mortem, but diagnostic accuracy deteriorates due to inability to definitively identify aggregated alpha-synuclein
Solution Approach 1:
The patent applies the taking out principle by extracting the diagnostic target (phosphorylated alpha-synuclein) from the inaccessible brain tissue and making it detectable in accessible peripheral tissues. Instead of requiring brain tissue analysis, the method detects the same pathologic phosphorylated alpha-synuclein aggregates in nerve fibers of skin, colon, or submandibular gland, thereby achieving definitive diagnostic accuracy ante-mortem through analysis of readily obtainable samples.
Solution Approach 2:
The patent uses accessible peripheral tissues (skin, colon, submandibular gland) as intermediaries to detect the presence of phosphorylated alpha-synuclein that would otherwise require brain tissue analysis. These peripheral tissues serve as mediators that contain nerve fibers with the same pathologic phosphorylated alpha-synuclein aggregates found in Parkinson's disease, allowing indirect but definitive diagnosis without needing to access the brain ante-mortem.
3Loss of time
If antibody-based detection methods are developed for ante-mortem diagnosis, then timely therapeutic intervention is enabled, but diagnostic reliability deteriorates without definitive identification of aggregated alpha-synuclein
Solution Approach 1:
The patent applies parameter changes by specifically detecting phosphorylated alpha-synuclein (with phosphorylation at residue S129) rather than total alpha-synuclein. This phosphorylation state is the pathologic form found in Parkinson's disease aggregates. By using antibodies that specifically recognize the phosphorylated form (such as antibody 7E2 or 3G2), the method achieves both ante-mortem timing and diagnostic reliability through detection of the specific pathologic modification rather than just the presence of alpha-synuclein protein.
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 ante-mortem diagnosis of PD, facilitating targeted 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
Data Source
AI summary
The invention provides methods and compositions for accurate identification and determination of Parkinson's disease ante-mortem tissue samples. The determination of Parkinson's disease is based on the binding of localized phosphorylated alpha-synuclein with the nerve feature. The methods disclosed in the invention may be used on myriad tissue types and could be manual or automated.