Anti-Alpha-Synuclein Antibodies for Truncated Protein Binding
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Solution Overview
Problem
Current antibodies targeting alpha-synuclein for treating synucleinopathies, such as Parkinson's disease, have limitations in binding to truncated forms of the protein, which are major species in pathological conditions, and do not effectively inhibit the spread of alpha-synuclein pathology between neurons.
Innovation Solution
Development of monoclonal antibodies, such as GM37 and GM285, that bind to the 112-117 epitope of alpha-synuclein, capable of neutralizing truncated forms and inhibiting the spread of alpha-synuclein pathology, and combinational treatments with additional medicaments to enhance therapeutic efficacy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current antibodies targeting alpha-synuclein are used, then they can bind to full-length alpha-synuclein, but they fail to bind to truncated forms which are major species in pathological conditions
Solution Approach 1:
The antibody is designed to target a specific local region (epitope at amino acids 112-117) of the alpha-synuclein protein. This localized targeting approach ensures that the antibody can recognize and bind to truncated forms of the protein that contain this epitope, while being specific to particular pathological species. The local quality principle resolves the contradiction by making the antibody's binding capability dependent on the presence of the specific epitope rather than requiring the full-length protein structure.
2Reliability
If current antibodies are used to treat synucleinopathies, then they target alpha-synuclein, but they do not effectively inhibit the spread of alpha-synuclein pathology between neurons
Solution Approach 1:
The antibody acts as an intermediary that binds to extracellular alpha-synuclein species and prevents their interaction with neuronal surfaces. By positioning itself between the pathogenic alpha-synuclein and the neurons, the antibody blocks the transmission of pathology. This mediator role directly addresses the contradiction by providing a mechanism to stop the spread of harmful factors while maintaining therapeutic targeting of alpha-synuclein.
3Measurement precision
If antibodies are designed to bind to specific epitopes, then they achieve high specificity, but they may not bind to various truncated forms of alpha-synuclein
Solution Approach 1:
The antibody is designed with universal binding capability to multiple truncated forms of alpha-synuclein while maintaining specificity for the pathological species containing the 112-117 epitope. This multi-functional design allows the single antibody to recognize various truncated variants (such as 1-119, 1-135, and other C-terminal truncated forms) that all retain the target epitope, thereby resolving the contradiction between specificity and versatility.
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 clear extracellular alpha-synuclein, normalize synaptic transmission, and prevent the appearance of disease-related motor phenotypes, demonstrating superior binding to various alpha-synuclein species and inhibiting neuronal pathology spread.
Implementation Method 1
monoclonal antibodies, such as GM37 and GM285, that bind to the 112-117 epitope of alpha-synuclein, capable of neutralizing truncated forms and inhibiting the spread of alpha-synuclein pathology
Data Source
AI summary
The invention relates to combinational treatment using a monoclonal anti-alpha-synuclein antibody and an additional medicament. The antibodies can be used for treating a synucleinopathy such as Parkinson's disease (including idiopathic and inherited forms of Parkinson's disease), Diffuse Lewy Body Disease (DLBD), Lewy body variant of Alzheimer's disease (LBV), Combined Alzheimer's and Parkinson disease, pure autonomic failure and multiple system atrophy together with another medicament of the invention.