Methods for identification, and compounds useful for the treatment of degenerative & inflammatory diseases

Abstract

The present invention relates to in vivo and in vitro methods, agents and compound screening assays for inhibiting extra-cellular matrix degradation, including joint degenerative inhibiting and/or anti-inflammatory pharmaceutical compositions, and the use thereof in treating and/or preventing a disease involving extra-cellular matrix degradation in a subject.

1 . A method for identifying a compound that inhibits extra-cellular matrix (ECM) degradation, comprising
 contacting a compound with a polypeptide comprising the amino acid sequence of SEQ ID NO: 39; and   measuring a compound-polypeptide property related to extra-cellular matrix (ECM) degradation.   
     
     
         2 . The method according to  claim 1 , wherein said polypeptide is in an in vitro cell-free preparation. 
     
     
         3 . The method of  claim 1 , wherein said property is a binding affinity of said compound to said polypeptide. 
     
     
         4 . The method according to  claim 1 , wherein said compound is selected from the group consisting of compounds of a commercially available screening library and compounds having binding affinity for a polypeptide comprising the amino acid sequence of SEQ ID NO: 39. 
     
     
         5 . The method according to  claim 2 , wherein said compound is a peptide in a phage display library or an antibody fragment library. 
     
     
         6 . The method of  claim 3 , further comprising the steps of
 selecting a compound that exhibits moderate or high binding affinity to said polypeptide;   contacting a population of mammalian cells with said compound; and   measuring a second compound-polypeptide property related to extra-cellular matrix (ECM) degradation.   
     
     
         7 . The method of  claim 6 , wherein said second compound-polypeptide property is activity of an ECM-degrading protein. 
     
     
         8 . The method of  claim 6 , wherein said second compound-polypeptide property is expression of an ECM-degrading protein. 
     
     
         9 . The method of  claim 7 , wherein said ECM-degrading protein is a Matrix Metallo Proteinase (MMP). 
     
     
         10 . The method of  claim 9 , wherein said MMP is selected from the group consisting of MMP1, MMP2, MMP3, MMP8, MMP9, MMP13 and MMP14. 
     
     
         11 . The method of  claim 10 , wherein said MMP is MMP1. 
     
     
         12 . The method of  claim 7 , wherein said ECM-degrading protein is Cathepsin K. 
     
     
         13 . The method of  claim 8 , wherein said ECM-degrading protein is a Matrix Metallo Proteinase (MMP). 
     
     
         14 . The method of  claim 13 , wherein said MMP is selected from the group consisting of MMP1, MMP2, MMP3, MMP8, MMP9, MMP13 and MMP14. 
     
     
         15 . The method of  claim 14 , wherein said MMP is MMP1. 
     
     
         16 . The method of  claim 8 , wherein said ECM-degrading protein is Cathepsin K.