Inhibition of trna synthetases and therapeutic applications thereof
AssigneePresident and Fellows of Harvard College
InventorsMalcolm Whitman, Tracy Keller
Life of this patent
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Abstract
The present invention provides novel methods for modulating Th 17-mediated immune responses using aminoacyl tRNA synthetase inhibitors. Inhibition of aminoacyl tRNA synthetase inhibitors activates an amino acid starvation response (AAR) and can produce beneficial therapeutic effects. In some embodiments, aminoacyl tRNA synthetase inhibitors are used to treat disorders such as autoimmune diseases, graft rejection, infections, fibrosis, and inflammatory diseases.
Claims28
A method of inhibiting an immune response mediated by IL-17 expressing T cells in a subject, the method comprising administering to the subject an agent that inhibits a eukaryotic aminoacyl tRNA synthetase, wherein the agent is administered in an amount effective to inhibit the aminoacyl tRNA synthetase in T cells in the subject.
4-5. (canceled)
10-12. (canceled)
(canceled)
22-31. (canceled)
A method of inhibiting one or more of fibrosis, angiogenesis, scar formation, cellulite formation or cellulite progression in a subject, the method comprising administering to the subject an agent that inhibits a eukaryotic aminoacyl tRNA synthetase, wherein the agent is administered in an amount effective to inhibit the aminoacyl tRNA synthetase in the subject.
34-47. (canceled)
A method of modulating differentiation of a T cell, the method comprising:
- contacting a T cell with an agent that inhibits a eukaryotic tRNA synthetase under conditions in which differentiation occurs, thereby modulating differentiation of the T cell.
49-55. (canceled)
A method of identifying an agent that modulates T cell differentiation, the method comprising:
- (a) contacting a T cell with an inhibitor of a eukaryotic aminoacyl tRNA synthetase under conditions in which T cell differentiation occurs, and
- (b) evaluating a marker of T cell differentiation, wherein a change in the marker of T cell differentiation, relative to a control, indicates that the inhibitor of the aminoacyl tRNA synthetase is an agent that modulates T cell differentiation.
57-61. (canceled)
A pharmaceutical composition comprising an agent that inhibits a eukaryotic aminoacyl tRNA synthetase in a pharmaceutically acceptable carrier.
63-65. (canceled)
Dependencies are inferred from the claim text.