Monoclonal Antibody Detection of Non-Phosphorylated α-Synuclein Aggregates
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current biomarkers for Lewy body dementias, such as Parkinson's disease and dementia with Lewy bodies, are inadequate in consistently correlating Lewy body pathology with clinical disease severity, particularly due to the lack of specificity in identifying non-phosphorylated alpha-synuclein aggregates.
Innovation Solution
Development of a monoclonal antibody that specifically binds to aggregated, non-phosphorylated alpha-synuclein, recognizing the epitope comprising amino acids 125-133 with a non-phosphorylated serine at position 129, and methods for generating and using such antibodies.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If pan-α-syn antibodies are used to detect Lewy body pathology, then both physiological and pathological forms of alpha-synuclein are recognized, but the correlation between Lewy body burden and clinical disease severity is inconsistent
Solution Approach 1:
The antibody is designed to recognize a specific local feature of alpha-synuclein - the non-phosphorylated state at serine 129 within aggregated forms. This local quality approach allows the antibody to distinguish pathological non-phosphorylated aggregates from both physiological monomers and phosphorylated pathological forms, thereby achieving precise correlation with disease severity while maintaining the ability to detect relevant pathological forms.
2Reliability
If antibodies target phosphorylated alpha-synuclein (pS129), then the predominant pathological form is detected, but early stage disease detection is limited since non-phosphorylated aggregates precede phosphorylated aggregates
Solution Approach 1:
The antibody targets non-phosphorylated alpha-synuclein aggregates, which are the precursor form that appears before phosphorylation occurs in the disease progression. By detecting this preliminary form, the antibody enables early stage disease detection before the more abundant phosphorylated forms accumulate, thus reducing the loss of time for early intervention while maintaining reliable detection of pathological aggregates.
3Quantity of substance
If current biomarkers are used for Lewy body dementias, then general alpha-synuclein aggregation is detected, but specificity for non-phosphorylated aggregates is insufficient
Solution Approach 1:
The antibody achieves high specificity by targeting the local chemical state of serine 129 in the context of aggregated alpha-synuclein. The antibody recognizes the non-phosphorylated state at this specific position within the aggregated conformation, allowing it to distinguish non-phosphorylated aggregates from both monomeric forms and phosphorylated aggregates, thereby providing both adequate quantity detection and high measurement precision.
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
The antibody provides high specificity and affinity for alpha-synuclein aggregates, allowing for early detection and potential therapeutic intervention in Lewy body dementias by targeting the unphosphorylated form, which precedes phosphorylated aggregates in the disease process.
Implementation Method 1
a monoclonal antibody that specifically binds aggregated, non-phosphorylated alpha-synuclein
Data Source
AI summary
The present specification provides a monoclonal antibody that specifically binds aggregated, non-phosphorylated α-synuclein and a hybridoma producing it. Also disclosed are methods of generating antibodies that specifically binds aggregated, non-phosphorylated α-synuclein and uses thereof. Uses of anti-α-synuclein antibody in detection and diagnostic assays, and for prophylaxis or therapy of α-synuclein-associated neurodegenerative diseases, are also disclosed.