Inhibitors of the PP1/GADD34 Complex for the Treatment of a Condition Requiring an Immunosuppressive Activity

Abstract

The present invention relates to the general field of the treatment and prevention of diseases involving an inflammatory condition, namely sepsis or infectious or viral diseases as well as diseases requiring for the of treatment an immunosuppressive activity namely autoimmune diseases and graft rejection. In particular, the invention relates to an inhibitor of the activity or the formation of the PP1/GADD34 complex for the treatment of a condition requiring an immunosuppressive activity or an anti-inflammatory activity.

1 - 15 . (canceled) 
     
     
         16 . A method of treating an inflammatory condition or an autoimmune disease in a patient in need thereof, comprising the step of
 administering to said patient a therapeutic amount of an inhibitor of activity or formation of a PP1/GADD34 complex.   
     
     
         17 . The method of  claim 16 , wherein said inflammatory condition is selected from the group consisting of an allergy, asthma, myopathy, cancer, acute respiratory distress syndrome (ARDS), systemic inflammatory response syndrome (SIRS), sepsis and an inflammatory condition caused by an infectious agent. 
     
     
         18 . The method of  claim 17 , wherein said inflammatory condition is sepsis. 
     
     
         19 . The method of  claim 17 , wherein said inflammatory condition is a viral disease. 
     
     
         20 . The method of  claim 19 , wherein said viral disease is caused by a virus selected from the group consisting of Chikungunya virus, influenza virus, herpes virus, avian influenza virus, smallpox virus and severe acute respiratory syndrome (SARS) virus. 
     
     
         21 . The method of  claim 19 , wherein said inflammatory condition is an autoimmune disease. 
     
     
         22 . The method of  claim 21 , wherein said autoimmune disease is graft rejection or graft versus host disease (GVHD). 
     
     
         23 . The method of  claim 16 , wherein said inhibitor is an inhibitor of GADD34. 
     
     
         24 . The method of  claim 16 , wherein said inhibitor is an inhibitor of PP1 in complex with GADD34. 
     
     
         25 . The method of  claim 16 , wherein said inhibitor inhibits an interaction domain comprising amino acid residues 540 to 600 of GADD34. 
     
     
         26 . The method of  claim 16 , wherein said inhibitor is selected from the groups consisting of salubrinal, tautomycine, calyculin A, a peptide comprising a fragment of GADD34 and a peptide consisting of a fragment of GADD34. 
     
     
         27 . The method of  claim 16 , wherein said inhibitor is a selective inhibitor of said PP1/GADD34 complex. 
     
     
         28 . The method of  claim 21 , wherein said autoimmune disease is selected from the group consisting of Sjögren's syndrome, systemic lupus erythematosus, psoriasis, dermatitis herpetiformis, vitiligo, mycosis fungoides, allergic contact dermatitis, atopic dermatitis, lichen planus, Pityriasis lichenoides et varioliforms acuta (PLEVA), arthritis, and catastrophic antiphospholipid syndrome. 
     
     
         29 . A therapeutic composition comprising
 an inhibitor of activity or formation of a PP1/GADD34 complex; and   a pharmaceutically acceptable carrier.