Compositions and methods for the modulation of jnk proteins

Abstract

The invention provides compositions and methods for the treatment and diagnosis of diseases or disorders amenable to treatment through modulation of expression of a gene encoding a Jun N-terminal kinase 1 (JNK1 protein.

1 - 10 . (canceled) 
     
     
         11 . A method of treating diabetes in a subject comprising administering to said subject a pharmaceutical composition comprising a glucose-lowering agent and a therapeutically effective amount of an antisense compound targeted to a JNK1 nucleic acid. 
     
     
         12 . A method of treating diabetes in a subject comprising administering to said subject a glucose-lowering agent and a therapeutically effective amount of an antisense compound targeted to a JNK1 nucleic acid. 
     
     
         13 . The method of  claim 12 , wherein the administering thereby reduces glucose levels or improves insulin sensitivity or both. 
     
     
         14 . The method of  claim 12 , wherein said glucose-lowering agent is insulin or an insulin-analog, a biguanide, a meglitinide, a thiazolidinedione, sulfonylurea or an alpha-glucosidase inhibitor. 
     
     
         15 . The method of  claim 14 , wherein the glucose lowering agent is a biguanide. 
     
     
         16 . The method of  claim 15 , wherein the biguanide is metformin. 
     
     
         17 . The method of  claim 14 , wherein the glucose lowering agent is a meglitinide. 
     
     
         18 . The method of  claim 17 , wherein the meglitinide is nateglinide or repaglinide. 
     
     
         19 . The method of  claim 14 , wherein the glucose lowering agent is a thiazolidinedione. 
     
     
         20 . The method of  claim 19 , wherein the thiazolidinedione is nateglinide pioglitazone, rosiglitazone, or troglitazone. 
     
     
         21 . The method of  claim 20 , wherein the glucose lowering agent is a rosiglitazone. 
     
     
         22 . The method of  claim 21 , wherein blood glucose levels are decreased and body weight is maintained or reduced. 
     
     
         23 . The method of  claim 14 , wherein the glucose lowering agent is an alpha-glucosidase inhibitor. 
     
     
         24 . The method of  claim 23 , wherein the alpha-glucosidase inhibitor is acarbose or miglitol. 
     
     
         25 . The method of  claim 14 , wherein the glucose lowering agent is sulfonylurea. 
     
     
         26 - 37 . (canceled) 
     
     
         38 . The method of  claim 12  wherein the glucose lowering agent and antisense compound are administered concomitantly. 
     
     
         39 . The method of  claim 12 , wherein the administering comprises parenteral administration. 
     
     
         40 . The method of  claim 39 , wherein the parenteral administration comprises subcutaneous or intravenous administration. 
     
     
         41 . (canceled) 
     
     
         42 . (canceled) 
     
     
         43 . The method of  claim 12 , wherein the antisense compound has at least 95% complementarity to SEQ ID NO: 87, 89, 90 or 91. 
     
     
         44 . The method of  claim 12 , wherein the antisense compound has 100% complementarity to SEQ ID NO: 87, 89, 90 or 91. 
     
     
         45 . The method of  claim 12 , wherein the antisense compound is 12 to 30 nucleosides in length. 
     
     
         46 - 48 . (canceled) 
     
     
         49 . The method of  claim 12 , wherein the antisense compound is an antisense oligonucleotide. 
     
     
         50 . The method of  claims 12 , wherein the antisense compound comprises at least one modified sugar moiety. 
     
     
         51 . The method of  claim 50 , wherein the modified sugar moiety is a 2′-O-methoxyethyl sugar moiety. 
     
     
         52 - 58 . (canceled)