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 . A method of treating autoimmune diseases in 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. 
     
     
         2 . The method of  claim 1  wherein said autoimmune disease is systemic lupus erythematosus. 
     
     
         3 . The method of  claim 1  wherein said autoimmune disease is arthritis. 
     
     
         4 . The method of  claim 1  wherein said autoimmune disease is Sjögren's syndrome. 
     
     
         5 . The method of  claim 1  wherein said autoimmune disease is selected from the group consisting of psoriasis, dermatitis herpetiformis, vitiligo, mycosis fungoides, allergic contact dermatitis, atopic dermatitis, lichen planus, Pityriasis lichenoides and varioliforms acuta (PLEVA). 
     
     
         6 . The method of  claim 1  wherein said autoimmune disease is catastrophic antiphospholipid syndrome. 
     
     
         7 . The method of  claim 1 , wherein said inhibitor inhibits an interaction domain comprising amino acid residues 540 to 600 of GADD34. 
     
     
         8 . The method of  claim 1 , wherein said inhibitor is selected from the group consisting of salubrinal, tautomycine, calyculin A, a peptide comprising a fragment of GADD34 and a peptide consisting of a fragment of GADD34. 
     
     
         9 . A method of treating graft rejection 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. 
     
     
         10 . The method of  claim 7  wherein the graft rejection concerns an allogenic transplant. 
     
     
         11 . The method of  claim 7  wherein the graft rejection concerns a Xenogenic transplant. 
     
     
         12 . The method of  claim 9 , wherein said inhibitor inhibits an interaction domain comprising amino acid residues 540 to 600 of GADD34. 
     
     
         13 . The method of  claim 9 , wherein said inhibitor is selected from the group consisting of salubrinal, tautomycine, calyculin A, a peptide comprising a fragment of GADD34 and a peptide consisting of a fragment of GADD34. 
     
     
         14 . A method of treating graft versus host disease (GVHD) 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. 
     
     
         15 . The method of  claim 14 , wherein said inhibitor inhibits an interaction domain comprising amino acid residues 540 to 600 of GADD34. 
     
     
         16 . The method of  claim 14 , wherein said inhibitor is selected from the group consisting of salubrinal, tautomycine, calyculin A, a peptide comprising a fragment of GADD34 and a peptide consisting of a fragment of GADD34.