ERAP2 Inhibition and HLA Allele Targeting for MHC-I-Opaties
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Solution Overview
Problem
There is a need for identifying and treating subjects with MHC-I-opathies, such as Birdshot Chorioretinopathy, Ankylosing Spondylitis, psoriasis with uveitis, and Juvenile Idiopathic Arthritis, by targeting ERAP2 activity through specific HLA alleles and inhibitors.
Innovation Solution
Administering a therapeutically effective amount of an ERAP2 inhibitor in combination with HLA-A29 or HLA-B27 inhibitory nucleic acid molecules to subjects with specific HLA alleles and functional ERAP2 proteins, as determined by genetic assays, to inhibit ERAP2 activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If ERAP2 activity is inhibited to treat MHC-I-opathies, then aberrant antigenic peptide generation is reduced, but the complexity of treatment protocols increases due to need for combination therapy with HLA inhibitors
Solution Approach 1:
The patent combines ERAP2 inhibitors with HLA-A29 or HLA-B27 inhibitory nucleic acid molecules into a single treatment protocol. This merging of therapeutic agents addresses the harmful effect of aberrant antigenic peptide generation while managing the complexity through integrated therapy rather than separate treatments.
Solution Approach 2:
The treatment protocol utilizes specific HLA alleles (HLA-A29 or HLA-B27) as selection parameters to identify suitable subjects. By changing the parameter of HLA allele specificity, the protocol achieves targeted treatment that reduces aberrant peptide generation while maintaining manageable treatment complexity through genetic screening criteria.
2Reliability
If combination therapy with ERAP2 inhibitor and HLA inhibitor is administered, then treatment effectiveness for MHC-I-opathies improves, but the cost and complexity of treatment increases
Solution Approach 1:
The patent merges ERAP2 inhibition and HLA inhibition into a unified treatment regimen that targets both pathways simultaneously. This combination approach improves treatment effectiveness for MHC-I-opathies by addressing multiple mechanisms of disease pathogenesis concurrently.
Solution Approach 2:
The protocol incorporates preliminary genetic screening to identify subjects with specific HLA alleles (HLA-A29 or HLA-B27) before initiating combination therapy. This preliminary action ensures that only suitable candidates receive the complex combination treatment, improving effectiveness while managing complexity through patient selection criteria.
3Device complexity
If ERAP2 inhibitor is administered alone, then treatment simplicity is maintained, but treatment effectiveness for certain MHC-I-opathies is reduced
Solution Approach 1:
The patent combines ERAP2 inhibitors with HLA-A29 or HLA-B27 inhibitory nucleic acid molecules to create a synergistic treatment approach. This merging enhances treatment effectiveness for MHC-I-opathies by simultaneously blocking both ERAP2-mediated peptide processing and HLA presentation, overcoming the limitations of monotherapy.
Solution Approach 2:
The treatment protocol utilizes HLA allele typing as a selection parameter to determine which subjects will benefit most from combination therapy. By changing the approach from single-agent to multi-agent therapy based on genetic parameters, the protocol achieves superior treatment effectiveness while maintaining clarity through structured patient selection criteria.
Data Source
AI summary
The present disclosure provides methods of treating subjects having an immune disorder by administering to the subject a therapeutically effective amount of an Endoplasmic Reticulum Aminopeptidase 2 (ERAP2) inhibitor in combination with an HLA-A29 or HLA-B27 inhibitory nucleic acid molecule.