Compositions and methods for treating autoimmune disease

Abstract

Methods and compositions are described for treating and diagnosing autoimmune diseases, and in particular for treating and detecting rheumatoid arthritis. Treatment is described with a new class of anti-RA drug, namely compounds that inhibit proliferation and induce apoptosis.

1 . A composition, comprising at least one inhibitor of the sphingomyelin signal transduction pathway in combination with DMSO.  
     
     
         2 . The composition of  claim 1 , wherein said inhibitor is a ceramide catabolism inhibitor.  
     
     
         3 . The composition of  claim 2 , wherein said ceramide catabolism inhibitor is selected from a group comprising N-oleoylethanolamine, (1S,2R)-D-erythro-2-(N-myristoylamino)-pheny-1-propanol, D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol or N-butyldeoxynojirimycin.  
     
     
         4 . The composition of  claim 1 , wherein said inhibitor is an inhibitor of sphingosine-phosphate formation.  
     
     
         5 . The composition of  claim 1 , wherein said inhibitor is an inhibitor of Gi proteins.  
     
     
         6 . The composition of  claim 1 , wherein said inhibitor is an inhibitor of Mitogenically Extraregulated Kinase 1 (MEK1).  
     
     
         7 . The composition of  claim 1 , wherein said inhibitor is an activator of Jun Kinase (JNK).  
     
     
         8 . The composition of  claim 1 , wherein said inhibitor is selected from a group comprising methylsphingosine, dimethylsphingosine, trimethylsphingosine, β-chloroalanine, L-cycloserine and fumonisin B1.  
     
     
         9 . A composition, comprising at least one inhibitor of the sphingomyelin signal transduction pathway, selected from the group consisting of methylsphingosine, dimethylsphingosine, (1S,2R)-D-erythro-2-(N-myristoylamino)-phenyl-1-propanol, N-butyldeoxynojirimycin and 2-(2′-amino-3′-methoxyphenyl-oxanaphthalen-4-one) in combination with DMSO.  
     
     
         10 . A method, comprising: 
 a) providing: i) a subject, and ii) a composition comprising at least one inhibitor of the sphingomyelin signal transduction pathway; and    b) administering said composition to said subject.    
     
     
         11 . The method of  claim 10 , wherein said composition is administered topically.  
     
     
         12 . The method of  claim 10 , wherein said composition further comprises DMSO.  
     
     
         13 . The method of  claim 10 , wherein said inhibitor is a ceramide catabolism inhibitor.  
     
     
         14 . The method of  claim 13 , wherein said ceramide catabolism inhibitor is selected from a group comprising N-oleoylethanolamine, (1S,2R)-D-erythro-2-(N-myristoylamino)-pheny-1-propanol, D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol or N-butyldeoxynojirimycin.  
     
     
         15 . The method of  claim 10 , wherein said inhibitor is an inhibitor of sphingosine-phosphate formation.  
     
     
         16 . The method of  claim 10 , wherein said inhibitor is an inhibitor of Gi proteins.  
     
     
         17 . The method of  claim 10 , wherein said inhibitor is an inhibitor of Mitogenically Extraregulated Kinase 1 (MEK1).  
     
     
         18 . The method of  claim 10 , wherein said inhibitor is an activator of Jun Kinase (JNK).  
     
     
         19 . The method of  claim 10 , wherein said inhibitor is selected from a group comprising methylsphingosine, dimethylsphingosine, trimethylsphingosine, β-chloroalanine, L-cycloserine and fumonisin B1.