Methods for Treating Heart Transplant Rejection

Abstract

Current therapeutic approach to treating heart allotransplantation rejection focus on immunosuppression protocols that carry harmful side effects after chronic use, which include global immune depression to the patient. The present inventors have discovered alternative and synergistic protocols based on inhibiting NF-κB and NLRP3 inflammasome-dependent IL-1βrelease with nitrated NSAID derivatives.

What is claimed is: 
     
         1 . A method of treating heart transplant rejection comprising administering to a subject in need thereof an effective amount of a compound of Formula I: 
       
         
           
           
               
               
           
         
       
     
     
         2 . The method of  claim 1 , further comprising administering one or more secondary therapeutic agents. 
     
     
         3 . The method of  claim 2 , wherein the one or more secondary therapeutic agents is selected from the group consisting of calcineurin inhibitors, corticosteroids, cytotoxic immunosuppressants, immunosuppressant antibodies, sirolimus derivatives, other immunosuppressants, and any combination thereof. 
     
     
         4 . A method of treating heart transplant rejection in a subject comprising administering to said subject a pharmaceutical composition comprised of an effective amount of a compound of Formula I: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt thereof, and a carrier. 
     
     
         5 . The method of  claim 4 , wherein the pharmaceutical composition further comprises one or more secondary therapeutic agents. 
     
     
         6 . The method of  claim 5 , wherein the one or more secondary therapeutic agents is selected from the group consisting of calcineurin inhibitors, corticosteroids, cytotoxic immunosuppressants, immunosuppressant antibodies, sirolimus derivatives, other immunosuppressants, and any combination thereof.