Compositions for diagnosis and therapy of diseases associated with aberrant expression of kremen and/or wnt

Abstract

The present invention relates to a composition useful for the diagnosis and therapy of diseases associated with aherrant expression of the gene encoding the receptor Kremen 1 and/or Kremen 2 e.g. tumors or diseases of the kidneys, bones and eyes, lipid and glucose metabolism and obesity. The present invention also relates to a pharmaceutical composition containing a compound which is capable of modifying (a) the expression of the gene encoding Kremen 1 and/or Kremen 2 or (b) the activity of the Kremen 1 and/or Kremen 2 receptor.

1 . Use of 
 (a) a nucleic acid molecule encoding human Kremen 1 and having the nucleotide sequence as depicted in  FIG. 1  or human Kremen 2 and having the nucleotide sequence as depicted in  FIG. 2 ,    (b) a nucleic acid molecule which is capable of specifically hybridizing to the nucleotide sequence encoding Kremen 1 as depicted in  FIG. 1  and/or to the nucleotide sequence encoding Kremen 2 as depicted in  FIG. 2 ; or    (c) at least one ligand which is capable of specifically binding to a Kremen 1 and/or Kremen 2 polypeptide.    for the preparation of a composition for diagnosis of a defect of the wnt/frz/LRP5,6 cascade.    
     
     
         2 . The use of  claim 1 , wherein the ligand is an antibody.  
     
     
         3 . The use of  claim 1  or  2 , wherein the nucleic acid molecule has a length of at least 10 nucleotides.  
     
     
         4 . The use of any one of  claims 1  to  3 , wherein the nucleic acid molecule or ligand are detectably labeled.  
     
     
         5 . The use of  claim 4 , wherein the label is selected from the group consisting of a radioisotope, a bioluminescent compound, a chemiluminescent compound, a fluorescent compound, a metal chelate, or an enzyme.  
     
     
         6 . The use of any one of  claims 1  to  5 , wherein the nucleic acid molecule or ligand are bound to a solid support.  
     
     
         7 . Use according to  claims 1  to  6 , wherein the target to which the nucleic acid molecule hybridizes is an mRNA.  
     
     
         8 . A method for identifying a binding partner to a Kremen 1 and/or Kremen 2 polypeptide comprising: 
 (a) contacting said polypeptide with a compound to be screened; and    (b) determining whether the compound effects an activity of said polypeptide or whether binding of the compound to said polypeptide has occured.    
     
     
         9 . A method for identifying activators/agonists or inhibitors/antagonists of a Kremen 1 and/or Kremen 2 polypeptide comprising the steps of: 
 (a) incubating a candidate compound with said polypeptide;    (b) assaying a biological activity, and    (c) determining if a biological activity of said polypeptide has been altered.    
     
     
         10 . Use of a nucleotide molecule encoding a polypeptide having a biological activity of Kremen 1 and/or Kremen 2, a Kremen 1 and/or Kremen 2 polypeptide, an activator/agonist of a Kremen 1 and/or Kremen 2 polypeptide or binding partner of said polypeptide(s) for the preparation of a pharmaceutical composition for inhibiting the Wnt signal cascade.  
     
     
         11 . Use according to  claim 10  for supporting regenerative processes.  
     
     
         12 . An activator/agonist or inhibitor/antagonist of a Kremen 1 and/or Kremen 2 polypeptide or binding partner of said polypeptide(s) obtainable by the method  claim 8  or  9 .  
     
     
         13 . A pharmaceutical composition comprising a compound which is capable of modulating the expression of a nucleic acid molecule (a) encoding human Kremen 1 and having the nucleotide sequence as depicted in  FIG. 1  or human Kremen 2 and having the nucleotide sequence as depicted in  FIG. 2  or (b) which is capable of specifically hybridizing to the nucleotide sequence encoding human Kremen 1 as depicted in  FIG. 1  and/or to the nucleotide sequence encoding human human Kremem 2 as depicted in  FIG. 2  or the activity of Kremen 1 and/or Kremen 2, and a pharmaceutically acceptable excipient, diluent or carrier.  
     
     
         14 . The pharmaceutical composition of  claim 13 , wherein the compound stimulates expression of the gene encoding Kremen 1 and/or Kremen 2 or the activity of Kremen 1 and/or Kremen 2.  
     
     
         15 . The pharmaceutical composition of  claim 13  or  14 , wherein the compound is a nucleotide molecule encoding a polypeptide having a biological activity of Kremen 1 and/or Kremen 2, a Kremen 1 and/or Kremen 2 polypeptide, an activator/agonist or inhibitor/antagonist of a Kremen 1 and/or Kremen 2 polypeptide or binding partner of said polypeptide(s) obtainable by the method of  claim 8  or  9 .