Anti-Alpha-Synuclein Antibodies for Fibril-Driven Aggregation Blocking
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current therapies for Parkinson's disease are inadequate in stopping the spread of alpha synuclein pathology and only provide symptomatic relief, while passive immune therapies targeting misfolded alpha synuclein show promise but require further development.
Innovation Solution
Development of anti-alpha synuclein antibodies with specific CDR sequences that bind to alpha synuclein monomers and fibrils, inhibiting aggregation and preventing the spread of alpha synuclein between neurons, with higher affinity for fibrils and specificity for alpha synuclein over other synucleins.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current therapies are used for Parkinson's disease, then symptomatic relief is provided, but the spread of alpha synuclein pathology cannot be stopped
Solution Approach 1:
The patent utilizes the harmful misfolded alpha synuclein aggregates (Lewy bodies) as targets for therapeutic intervention. By designing antibodies that specifically recognize and bind to misfolded alpha synuclein conformations, the therapy converts the harmful pathogenic protein into a targetable antigen, enabling the immune system to clear the pathology while preserving normal alpha synuclein function.
Solution Approach 2:
The patent introduces monoclonal antibodies as intermediary molecules that mediate between the immune system and misfolded alpha synuclein. These antibodies serve as bridges that enable immune cells to recognize and eliminate pathological alpha synuclein aggregates without directly interacting with the pathogen itself, thereby providing a controlled and specific therapeutic mechanism.
2Reliability
If anti-alpha synuclein antibodies are designed to bind fibrils with high affinity, then aggregation is inhibited, but binding to monomeric alpha synuclein may increase off-target effects
Solution Approach 1:
The patent applies local quality by designing antibodies with CDR regions specifically optimized to recognize the unique conformational epitopes present on misfolded alpha synuclein aggregates. The complementarity determining regions (CDRs) are engineered to match the specific structural features of pathological conformations (beta-sheet rich aggregates) while maintaining tolerance for variability in monomeric forms, thereby achieving selective binding through localized structural recognition.
Solution Approach 2:
The patent utilizes parameter changes by optimizing the binding affinity characteristics of the antibodies. The antibodies are designed with dissociation constants (KD) in the nanomolar to picomolar range for misfolded alpha synuclein, representing a significant enhancement in binding strength compared to conventional antibodies. This parameter optimization ensures high-affinity binding to pathological aggregates while maintaining selectivity through conformation-specific recognition.
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 antibodies effectively inhibit alpha synuclein aggregation and reduce Lewy body pathology, improving motor impairments and neuronal loss, offering a therapeutic approach for Parkinson's disease and other synucleinopathies.
Implementation Method 1
anti-alpha synuclein antibodies with specific CDR sequences that bind to alpha synuclein monomers and fibrils
Data Source
AI summary
The present invention relates to antibodies binding alpha synuclein and fragments thereof capable of binding alpha synuclein as a monomer and in fibrils and preventing alpha synuclein aggregation induced by alpha synuclein fibrils. The antibodies of the present invention are for use in the treatment of alpha synucleinopathies, including Parkinson's disease.