Inhibitors of Cathepsin S for Prevention or Treatment of Obesity-Associated Disorders

Abstract

The present invention relates to methods (and pharmaceutical compositions) for treating and/or preventing for obesity associated disorders, particularly related to a deregulation of glucose homeostasis, by administrating Cathepsin S inhibitors. The invention also relates to methods for diagnosing insulin resistance and glucose tolerance by measuring Cathepsin S levels in a biological sample obtained from a subject.

1 - 6 . (canceled) 
     
     
         7 . A method for reducing glucose production in a subject in need thereof to treat or prevent obesity-associated disorders selected from the group consisting of type 2 diabetes, hyperglycemia, glucose intolerance or dyslipidemia, insulin resistance, hyperinsulinemia, and hepatic disease, comprising the step of administering to said subject an effective amount of an inhibitor of Cathepsin S. 
     
     
         8 . The method of  claim 7  wherein said subject is an obese subject. 
     
     
         9 . The method of  claim 8  wherein inhibition of Cathepsin'S ameliorates glucose homeostasis in said obese subject. 
     
     
         10 . The method of  claim 7  wherein said inhibitor of Cathepsin S is a selective inhibitor. 
     
     
         11 . The method of  claim 10  wherein said selective inhibitor is an antibody or aptamer. 
     
     
         12 . The method of  claim 7  wherein said inhibitor of Cathepsin S is an inhibitor of Cathepsin S expression. 
     
     
         13 . The method of  claim 12  wherein said inhibitor of Cathepsin S expression is an anti-sense RNA molecule or an anti-sense DNA molecule. 
     
     
         14 . The method of  claim 12  wherein said inhibitor of Cathepsin S expression is siRNA or shRNA. 
     
     
         15 . A method for treating glucose homeostasis in a subject in need thereof, comprising the step of administering to said subject an effective amount of an inhibitor of Cathepsin S. 
     
     
         16 . The method of  claim 15  wherein said subject is an obese subject. 
     
     
         17 . The method of  claim 16  wherein inhibition of Cathepsin S ameliorates glucose homeostasis in said obese subject. 
     
     
         18 . The method of  claim 15  wherein said inhibitor of Cathepsin S is a selective inhibitor. 
     
     
         19 . The method of  claim 18  wherein said selective inhibitor is an antibody or aptamer. 
     
     
         20 . The method of  claim 15  wherein said inhibitor of Cathepsin S is an inhibitor of Cathepsin S expression. 
     
     
         21 . The method of  claim 20  wherein said inhibitor of Cathepsin S expression is an anti-sense RNA molecule or an anti-sense DNA molecule. 
     
     
         22 . The method of  claim 20  wherein said inhibitor of Cathepsin S expression is siRNA or shRNA. 
     
     
         23 . A pharmaceutical composition formulated for administration to a subject that has or is at risk of having an obesity-associated disorder comprising a vehicle and a vector for transferring oligonucleotide, siRNA, shRNA, or ribozyme nucleic acids to cells of said subject which inhibit Cathepsin S expression.