Targeting MicroRNAs for Metabolic Disorders

Abstract

Described herein are compounds comprising modified oligonucleotides that are complementary to miR-103 and/or miR-107 and methods of treating diseases and disorders using the compounds.

1 . to  49 . (canceled) 
     
     
         50 . A method for reducing a blood glucose level of a subject having an elevated blood glucose level or preventing or delaying the onset of an elevated blood glucose level in a subject at risk for developing an elevated glucose level, comprising administering to the subject a therapeutically effective amount of a compound comprising the structure (II): 
       
         
           
           
               
               
           
         
       
       wherein X is a phosphodiester linkage; each N of Nm is a deoxyadenosine (A); m is 2; Y is a phosphodiester linkage; and MO is 5′-C S A S A S U S G S C S U S G S C S A S AAC S A S A S U S G S C S U S G S C S A S - 3′, wherein each nucleoside followed by a subscript “S” is a S-cEt nucleoside, each nucleoside not followed by a subscript is a deoxynucleoside, and each internucleoside linkage between two S-cEt nucleosides is a phosphorothioate linkage, and the remaining internucleoside linkages are phosphodiester linkages; and wherein Y is linked to the 3′ terminus of MO, wherein the compound is comprised in a pharmaceutical composition. 
     
     
         51 . The method of  claim 50 , wherein the subject has type 2 diabetes. 
     
     
         52 . The method of  claim 50 , wherein the subject has non-alcoholic steatohepatitis (NASH). 
     
     
         53 . The method of  claim 52 , wherein the subject has type 2 diabetes. 
     
     
         54 . The method of  claim 52 , wherein the subject has pre-diabetes. 
     
     
         55 . The method of  claim 50 , wherein the subject has non-alcoholic fatty liver disease. 
     
     
         56 . The method of  claim 55 , wherein the subject has type 2 diabetes. 
     
     
         57 . The method of  claim 55 , wherein the subject has pre-diabetes. 
     
     
         58 . The method of  claim 50 , wherein the pharmaceutical composition comprises a pharmaceutically acceptable carrier. 
     
     
         59 . The method of  claim 58 , wherein the pharmaceutical composition is an aqueous composition. 
     
     
         60 . A method for reducing a blood glucose level of a subject having an elevated blood glucose level or preventing or delaying the onset of an elevated blood glucose level in a subject at risk for developing an elevated glucose level, comprising administering to the subject a therapeutically effective amount of a compound having the structure: 
       
         
           
           
               
               
           
         
       
       wherein the compound is comprised in a pharmaceutical composition. 
     
     
         61 . The method of  claim 60 , wherein the subject has type 2 diabetes. 
     
     
         62 . The method of  claim 60 , wherein the subject has non-alcoholic steatohepatitis (NASH). 
     
     
         63 . The method of  claim 62 , wherein the subject has type 2 diabetes. 
     
     
         64 . The method of  claim 62 , wherein the subject has pre-diabetes. 
     
     
         65 . The method of  claim 60 , wherein the subject has non-alcoholic fatty liver disease. 
     
     
         66 . The method of  claim 65 , wherein the subject has type 2 diabetes. 
     
     
         67 . The method of  claim 65 , wherein the subject has pre-diabetes. 
     
     
         68 . The method of  claim 60 , wherein the pharmaceutical composition comprises a pharmaceutically acceptable carrier. 
     
     
         69 . The method of  claim 68 , wherein the pharmaceutical composition is an aqueous composition.