Coronin 1 Modulators for T Cell Homeostasis and Mycobacterial Infection
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Solution Overview
Problem
Current treatments for mycobacterial infections, autoimmune disorders, and lymphoproliferative disorders, as well as immunosuppression following transplantation, are inadequate in effectively managing T cell homeostasis and mycobacterial survival within macrophages.
Innovation Solution
Administration of coronin 1 or its modulators, which regulate T cell survival and mycobacterial infection by influencing the calcineurin pathway, using compounds such as cyclosporin A and tacrolimus, and screening for candidate compounds that selectively modulate coronin 1 activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current treatments are used for mycobacterial infections and autoimmune disorders, then existing therapeutic approaches are maintained, but T cell homeostasis cannot be effectively managed and mycobacterial survival within macrophages persists
Solution Approach 1:
The patent employs calcineurin modulators (cyclosporin A and tacrolimus) that alter the biochemical parameters of the calcineurin pathway, specifically inhibiting calcineurin phosphatase activity. This parameter change in enzyme activity leads to sustained NFAT phosphorylation and altered gene expression, thereby effectively managing T cell homeostasis and preventing mycobacterial survival in macrophages
2Object-generated harmful factors
If coronin 1 modulators are administered to treat mycobacterial infections and autoimmune disorders, then T cell depletion and disease treatment are achieved, but the complexity of the treatment mechanism increases due to calcineurin pathway involvement
Solution Approach 1:
The patent introduces coronin 1 modulators as intermediary compounds that bridge the gap between conventional treatments and the desired immunosuppressive effect. These modulators act as mediators by binding to coronin 1 and indirectly influencing the calcineurin-NFAT pathway, thereby achieving T cell depletion and disease treatment through a controlled intermediate mechanism rather than direct intervention
3Reliability
If calcineurin modulators such as cyclosporin A and tacrolimus are used, then immunosuppression is achieved, but the specificity of T cell regulation is reduced
Solution Approach 1:
The patent segments the immunosuppressive effect into two distinct mechanisms: (1) direct inhibition of calcineurin phosphatase activity by modulators like cyclosporin A and tacrolimus, and (2) indirect modulation through coronin 1 interaction. This segmentation allows for differentiated regulation where calcineurin inhibition provides broad immunosuppression while coronin 1 modulation adds a layer of specific T cell control, thereby maintaining both reliability and specificity
Data Source
AI summary
The invention relates to the treatment of mycobacterial infections, autoimmune disorders, lymphoproliferative disorders and induction of immunosuppression following transplantation using coronin 1 and modulators of coronin 1. Particular modulators of coronin 1 are compounds which inhibit the production of coronin 1 or the formation of active coronin 1 from a coronin 1 precursor, partly or entirely inactivate coronin 1, inhibit concentration of coronin 1 at the site of T cell activation, or inhibit the coronin 1 mediated signaling pathway downstream of the T cell receptor. Examples of such modulators are antibody or antibody fragments, coronin 1 peptide fragments or corresponding phosphopeptides, or anti-sense oligonucleotides, e.g. siRNA or shRNA. The invention further relates to a method of screening for a compound effective in the treatment of mycobacterial infections, autoimmune disorders, lymphoproliferative disorders and induction of immunosuppression following transplantation comprising contacting a candidate compound with coronin 1 or coronin 1 expressing cells, and selecting appropriate compounds.