Anti-Alpha-Synuclein Antibodies Blocking Fibril Spread Between Neurons
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Solution Overview
Problem
Current therapies for Parkinson's disease and other synucleinopathies are unable to stop the spread of alpha synuclein misfolded proteins, which form toxic oligomers and aggregates, leading to neurodegeneration, and only provide symptomatic relief.
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 than monomers.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If current symptomatic therapies are used for Parkinson's disease, then symptom relief is provided, but the spread of alpha synuclein misfolded proteins and neurodegeneration are not stopped
Solution Approach 1:
The patent introduces anti-alpha synuclein antibodies as intermediary molecules that bind to misfolded alpha synuclein proteins and toxic oligomers, preventing their spread between neurons. These antibodies act as mediators that interfere with the pathogenic mechanism without requiring the complex cellular machinery to produce therapeutic proteins, thereby providing a more reliable therapeutic approach against the spread of misfolded proteins
Solution Approach 2:
The patent leverages the body's own immune system to combat the disease. By administering anti-alpha synuclein antibodies, the harmful misfolded proteins trigger an immune response that produces beneficial therapeutic effects. The antibodies bind to and neutralize the toxic oligomers and aggregates, converting the harmful presence of misfolded proteins into an opportunity for immune-mediated clearance and protection
2Object-generated harmful factors
If alpha synuclein forms toxic oligomers and aggregates, then neurodegeneration is caused, but the ability to stop aggregation spread is lost
Solution Approach 1:
The patent applies preliminary anti-action by administering anti-alpha synuclein antibodies before extensive neurodegeneration occurs. These antibodies preemptively bind to misfolded alpha synuclein and toxic oligomers, preventing their propagation to healthy neurons. The therapeutic approach acts in advance to block the aggregation spread mechanism rather than attempting to reverse established damage
Solution Approach 2:
The anti-alpha synuclein antibodies serve as intermediary molecules that physically intervene in the aggregation process. They bind to misfolded proteins and toxic oligomers, acting as a barrier that prevents these harmful structures from spreading between neurons. This intermediary action provides a mechanistic means to stop aggregation spread that does not require complex cellular manufacturing processes
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 neurodegeneration by blocking the spread of toxic oligomers, offering a therapeutic approach to treat synucleinopathies such as Parkinson's disease.
Implementation Method 1
an antibody or antigen-binding fragment thereof which binds to alpha synuclein wherein the antibody or fragment thereof comprises: a light chain variable region comprising a CDR-L1 selected from SEQ ID NO: 1; a CDR-L2 according to SEQ ID NO: 2 and a CDR-L3 according to SEQ ID NO: 3; and a heavy chain variable region comprising a CDR-H1 according to SEQ ID NO: 4; a CDR-H2 selected from SEQ ID NO: 5 and a CDR-H3 selected from SEQ ID NO: 6
Data Source
AI summary
The present invention relates to alpha synuclein binding antibodies 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.