MHC Class Ib Polypeptides for Alpha-Synuclein Tolerance
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Solution Overview
Problem
Current treatments for Parkinson's disease, such as administering L-Dopamine or immunosuppressants, do not prevent disease progression and often come with significant side effects, while existing immunotherapies like cinpanemab fail to effectively target alpha-Synuclein aggregation, highlighting the need for targeted and specific immunomodulatory drugs.
Innovation Solution
Recombinant polypeptides comprising peptide antigens and domains of non-classical MHC class Ib molecules, particularly HLA-G, are designed to induce antigen-specific tolerance by suppressing immune responses against alpha-Synuclein, using covalently linked components like HLA-G, β2-microglobulin, and optional domains of MHC class I molecules to achieve targeted immunomodulation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If L-Dopamine or derivative substances are administered to compensate for SN neuron loss, then disease symptoms are initially improved, but disease progression is not prevented
Solution Approach 1:
Instead of compensating for neuron loss with L-Dopamine, the invention inverts the approach by using MHC class Ib molecules to modulate the immune system's response to alpha-Synuclein, thereby preventing the underlying pathological process rather than just masking symptoms
Solution Approach 2:
The patent introduces MHC class Ib molecules as intermediary substances that mediate between the immune system and alpha-Synuclein, creating a tolerogenic environment that prevents neuroinflammation and disease progression without directly replacing dopamine
2Object-generated harmful factors
If strong immunosuppressants are used to treat PD, then immune responses are suppressed, but significant side effects occur
Solution Approach 1:
The invention applies local quality by using MHC class Ib molecules to induce antigen-specific tolerance only against alpha-Synuclein, rather than systemic immunosuppression, thereby suppressing harmful immune responses locally at the target antigen level while preserving overall immune function
Solution Approach 2:
The patent changes the parameter of immune suppression from broad and strong (systemic immunosuppressants) to specific and targeted (antigen-specific tolerance induction via MHC class Ib molecules), altering the nature of immune modulation to reduce side effects
3Productivity
If MHC class Ia molecules are used to present peptide antigens, then immune responses are activated, but antigen-specific tolerance is not induced
Solution Approach 1:
The invention inverts the function of MHC molecules by using class Ib molecules (known for tolerance induction) instead of class Ia molecules (known for immune activation), thereby achieving the opposite effect of what class Ia molecules produce
Data Source
AI summary
The present invention relates to therapeutical uses of non-classical human major histocompatibility complex (MHC) molecules (also named MHC class Ib molecules) in combination with peptide antigens for the treatment of Parkinson's disease. The invention more specifically relates to recombinant polypeptides comprising peptide antigens and one or more domains of a non-classical MHC class Ib molecule. The invention also relates to methods of producing such recombinant polypeptides, pharmaceutical compositions comprising the same, as well as their uses for treating Parkinson's disease.