Modulation of the Transcription of Pro-Inflammatory Gene Products

Abstract

The present invention refers to inhibitors of the transcription factors IRF-1, their use as therapeutic agents as well as their use for prevention and therapy of cardiovascular complications like re-stenosis after percutaneous angioplasty or stenosis of venous bypasses, chronic (transplant arteriosclerosis or vasculopathy) or acute transplant rejection, graft versus host disease (GVHD), immunological hypersensitivity reactions (allergies), particularly bronchial asthma and atopic dermatitis, chronic recurrent inflammatory diseases, particularly ulcerative colitis and Crohn's disease, psoriasis and sarcoidosis, as well as autoimmune diseases, particularly diabetes mellitus, multiple sclerosis, collagenoses (e.g. systemic lupus erythematodes), rheumatoid arthritis and vasculotids.

1 . An inhibitor of the IRF-1 expression and/or activity as therapeutic substance. 
     
     
         2 . The inhibitor according to  claim 1 , wherein the inhibitor is a double stranded DNA molecule and inhibits the IRF-1 activity. 
     
     
         3 . The inhibitor according to  claim 2  having a nucleic acid sequence according to SEQ ID NO: 1 to 22. 
     
     
         4 . The inhibitor according to  claim 2 , wherein the double stranded DNA molecule exhibits modified internucleotide linkages. 
     
     
         5 . The inhibitor according to  claim 1 , wherein the inhibitor is an antisense oligonucleotide and inhibits the IRF-1 expression. 
     
     
         6 . The inhibitor according to  claim 5  having a nucleic acid sequence according to SEQ ID NO:23 to 26. 
     
     
         7 . The inhibitor according to  claim 5 , wherein the antisense oligonucleotide exhibits modified internucleotide linkages. 
     
     
         8 . A method for the prevention or therapy of cardiovascular complications chronic (graft atherosclerosis or vasculopathy) or acute transplant rejection, graft versus host disease (GVAD), immunological hypersensitivity reactions (allergies), chronic recurrent inflammation, psoriasis and sarcoidosis, disease or autoimmune disease, comprising administering to a subject in need thereof an inhibitor of IRF-1. 
     
     
         9 . An antisense oligonucleotide having a nucleic acid sequence according to SEQ ID NO:23 to 26. 
     
     
         10 . The antisense oligonucleotide according to  claim 9 , wherein the antisense oligonucleotide exhibits modified internucleotide linkages. 
     
     
         11 . A double-stranded DNA molecule having a nucleic acid sequence according to SEQ ID NO:1 to 21. 
     
     
         12 . The double-stranded DNA molecule according to 11, wherein the double stranded DNA molecule exhibits modified internucleotide linkages. 
     
     
         13 . The method of  claim 8 , wherein said cardiovascular complication is selected from the group consisting of restenosis after percutaneous angioplasty or the stenosis of venous bypasses. 
     
     
         14 . The method of  claim 8 , wherein the immunological hypersensitivity reaction is selected from the group consisting of bronchial asthma and atopic dermatitis 
     
     
         15 . The method of  claim 8 , wherein the chronic recurrent inflammation diseases is selected from the group consisting of colitis ulcerosa and Morbus Crohn. 
     
     
         16 . The method of  claim 8 , wherein the autoimmune disease is selected from the group consisting of diabetes mellitus, multiple sclerosis, collagenosis (for example systemic Lupus erythematodes), rheumatoid arthritis and vasculotids.