Use of fkbp-l polypeptides and nucleic acids for the treatment of obesity

Abstract

The inventors have determined that increasing the expression level or activity of FKBP-L polypeptide in a subject, which can be provided by expression of nucleic acids encoding FKBP-L or by providing FKBP-L polypeptides to a subject is advantageous for use in the treatment of obesity and obesity-related disorders. In particular increased expression or activity of FKBP-L polypeptide in a subject may be used to treat excessive weight gain (which can be characterised as obesity), glucose intolerance, diabetes and metabolic syndrome, which are closely linked to obesity and insulin resistance. FKBP-L can also be used as a biomarker for obesity and obesity-related disorders.

1 . A FKBP-L polypeptide, a biologically active fragment of an FKBP-L polypeptide, a derivative of FKBP-L polypeptide, or a derivative of a biologically active fragment of an FKBP-L polypeptide, or a nucleic acid sequence capable of being expressed in a subject to provide FKBP-L or a biologically active fragment or derivative thereof for use in treating obesity or obesity-related disorders. 
     
     
         2 . A FKBP-L polypeptide, a biologically active fragment of an FKBP-L polypeptide, a derivative of FKBP-L polypeptide, or a derivative of a biologically active fragment of an FKBP-L polypeptide, or a nucleic acid sequence capable of being expressed in a subject to provide FKBP-L or a biologically active fragment or derivative thereof for use in treating obesity and obesity-related disorders according to  claim 1 , wherein the FKBP-L polypeptide comprises the amino acid sequence shown in SEQ ID NO: 2, or SEQ ID NO: 29. 
     
     
         3 . A FKBP-L polypeptide, a biologically active fragment of an FKBP-L polypeptide, a derivative of FKBP-L polypeptide, or a derivative of a biologically active fragment of an FKBP-L polypeptide, or a nucleic acid sequence capable of being expressed in a subject to provide FKBP-L or a biologically active fragment or derivative thereof for use in treating obesity and obesity-related disorders according to  claim 1 , wherein the biologically active fragment of FKBP-L comprises or consists of the amino acid sequence shown in any one of SEQ ID NOs: 3 to 28. 
     
     
         4 . A FKBP-L polypeptide, a biologically active fragment of an FKBP-L polypeptide, a derivative of FKBP-L polypeptide, or a derivative of a biologically active fragment of an FKBP-L polypeptide, or a nucleic acid sequence capable of being expressed in a subject to provide FKBP-L or a biologically active fragment or derivative thereof for use in treating obesity and obesity-related disorders according to  claim 1 , wherein the biologically active fragment of FKBP-L consists of the amino acid sequence 
       
         
           
                 
                 
               
                     
                   NH2-IRQQPRDPPTETLELEVSPDPAS-OH (ALM201) 
                 
                     
                   or 
                 
                     
                     
                 
                     
                   NH2-QIRQQPRDPPTETLELEVSPDPAS-OH (AD-01). 
                 
             
                
                
                
                
               
            
           
         
       
     
     
         5 . A FKBP-L polypeptide, a biologically active fragment of an FKBP-L polypeptide, a derivative of FKBP-L polypeptide, or a derivative of a biologically active fragment of an FKBP-L polypeptide, or a nucleic acid sequence capable of being expressed in a subject to provide FKBP-L or a biologically active fragment or derivative thereof for use in treating obesity and obesity-related disorders according to  claim 1 , wherein the obesity-related disorder is type 2 diabetes. 
     
     
         6 . A FKBP-L polypeptide, a biologically active fragment of an FKBP-L polypeptide, a derivative of FKBP-L polypeptide, or a derivative of a biologically active fragment of an FKBP-L polypeptide, or a nucleic acid sequence capable of being expressed in a subject to provide FKBP-L or a biologically active fragment or derivative thereof for use in treating obesity and obesity-related disorders according to  claim 1 , wherein the FKBP-L polypeptide, biologically active fragment or derivative of a FKBP-L polypeptide is provided in combination with at least one pharmacologically active agent(s) that is (are) useful in the treatment of obesity or obesity-related disorders. 
     
     
         7 . A pharmaceutical formulation for use in the treatment of obesity or obesity-related disorders comprising a FKBP-L polypeptide, a biologically active fragment of an FKBP-L polypeptide, a derivative of FKBP-L polypeptide, or a derivative of a biologically active fragment of an FKBP-L polypeptide, or a nucleic acid sequence capable of being expressed in a subject to provide FKBP-L or a biologically active fragment or derivative thereof for use in treating obesity and obesity-related disorders and at least one pharmaceutical carrier, wherein a FKBP-L polypeptide, or a biologically active fragment or a derivative thereof is present in an amount effective for use in the treatment of obesity and obesity-related disorders. 
     
     
         8 . A method of treating obesity or an obesity-related disorder comprising the step of administering to a subject in need thereof a FKBP-L polypeptide, a biologically active fragment of an FKBP-L polypeptide, a derivative of FKBP-L polypeptide, or a derivative of a biologically active fragment of an FKBP-L polypeptide, or a nucleic acid sequence capable of being expressed in a subject to provide FKBP-L or a biologically active fragment or derivative thereof. 
     
     
         9 . The method of  claim 8  wherein the FKBP-L polypeptide comprises the amino acid sequence shown in SEQ ID NO: 2, or SEQ ID NO: 29. 
     
     
         10 . The method of  claim 8  wherein the FKBP-L polypeptide comprises or consists of the amino acid sequence shown in any one of SEQ ID NOs: 3 to 28. 
     
     
         11 . The method of  claim 8  wherein the FKBP-L polypeptide consists of the amino acid sequence NH2-IRQQPRDPPTETLELEVSPDPAS-OH (ALM201) or NH2-QIRQQPRDPPTETLELEVSPDPAS-OH (AD-01). 
     
     
         12 . A FKBP-L polypeptide, a biologically active fragment of an FKBP-L polypeptide, a derivative of FKBP-L polypeptide, or a derivative of a biologically active fragment of an FKBP-L polypeptide, or a nucleic acid sequence capable of being expressed in a subject to provide FKBP-L or a biologically active fragment or derivative thereof for use in treating obesity and obesity-related disorders according to  claim 1 , wherein obesity is at least one condition selected from excessive weight gain, glucose intolerance, diabetes and metabolic syndrome. 
     
     
         13 . A FKBP-L polypeptide, a biologically active fragment of an FKBP-L polypeptide, a derivative of FKBP-L polypeptide, or a derivative of a biologically active fragment of an FKBP-L polypeptide, or a nucleic acid sequence capable of being expressed in a subject to provide FKBP-L or a biologically active fragment or derivative thereof for use in treating obesity and obesity-related disorders according to  claim 1 , wherein the nucleic acid is provided in combination with a RALA peptide.