Pharmaceutical compositions comprising fragments and homologs of troponin subunits

Abstract

The present invention relates to pharmaceutical compositions comprising therapeutically effective amounts of troponin C, I or T subunits, fragments or homologs for the treatment of diseases or disorders involving abnormal angiogenesis and methods of use thereof.

1 . A pharmaceutical composition comprising an amount of a peptide that is effective to inhibit angiogenesis, in which the peptide is: 
 a. an inhibitor of bFGF-stimulated bovine endothelial cell proliferation having an IC 50  of 10 μM or less;    b. greater than 75 amino acids in length; and    C. greater than 80% homologous with a subunit selected from the group consisting of human fast-twitch troponin subunit C (SEQ ID NO:1), human fast-twitch troponin subunit I (SEQ ID NO: 2), and human fast-twitch troponin subunit T (SEQ ID NO: 3); and    a pharmaceutically acceptable carrier.    
     
     
         2 . The composition of  claim 1 , in which the subunit is human fast-twitch troponin C or human fast-twitch tropinin I.  
     
     
         3 . The composition of  claim 1 , in which the subunit is human fast-twitch troponin C.  
     
     
         4 . The composition of  claim 1 , in which the subunit is human fast-twitch troponin I.  
     
     
         5 . The composition of  claim 1 , in which the peptide is greater than 95% homologous with a human troponin subunit.  
     
     
         6 . The composition of  claim 5 , in which the subunit is human fast-twitch troponin C.  
     
     
         7 . The composition of  claim 5 , in which the subunit is human fast-twitch troponin I.  
     
     
         8 . The composition of  claim 1 , in which the peptide is a mammalian troponin subunit.  
     
     
         9 . The composition of  claim 8 , in which the peptide is a mammalian troponin C or troponin I subunit.  
     
     
         10 . The composition of  claim 9 , in which the peptide is a troponin subunit selected from the group consisting of bovine, rabbit, mouse and rat troponin subunits.  
     
     
         11 . The composition of  claim 8 , in which the peptide is a human troponin C or troponin I subunit.  
     
     
         12 . The composition of  claim 8 , in which the peptide is a troponin subunit selected from the group consisting of bovine, rabbit, mouse and rat troponin subunits.  
     
     
         13 . The composition of  claim 1 , in which the peptide is a fragment of a mammalian troponin subunit.  
     
     
         14 . The composition of  claim 13 , in which the peptide is a fragment of a human troponin C or troponin I subunit.  
     
     
         15 . The composition of  claim 13 , in which the peptide is a fragment of a troponin I or troponin C subunit selected from the group consisting of bovine, rabbit, mouse and rat troponin C and I subunits.  
     
     
         16 . The composition of  claim 1 , wherein the carrier is acceptable for topical application to the eye.  
     
     
         17 . The composition of  claim 1 , wherein the carrier is acceptable for topical application to the skin.  
     
     
         18 . The composition of  claim 1 , wherein the angiogenesis inhibitor is in a biodegradable, biocompatible polymeric delivery device.  
     
     
         19 . A method of inhibiting atopic angiogenesis in a subject, having a disease or disorder causing atopic angiogenesis requiring such inhibition, which comprising the step of applying to a site of atopic angiogenesis an amount of a peptide that is effective to inhibit angiogenesis, in which the peptide is: 
 a. an inhibitor of bFGF-stimulated bovine endothelial cell proliferation having an IC 50  of 10 μM or less;    b. greater than 75 amino acids in length; and    c. greater than 80% homologous with a subunit selected from the group consisting of human fast-twitch troponin I subunit, human fast-twitch troponin C subunit and human fast-twitch troponin T subunit.    
     
     
         20 . The method of  claim 19 , in which the subunit is human fast-twitch troponin C or human fast-twitch troponin I.  
     
     
         21 . The method of  claim 20 , in which the disease or disorder is a solid tumor.  
     
     
         22 . The method of  claim 20 , in which the tumor is a tumor of the central nervous system.  
     
     
         23 . The method according to  claim 20 , in which the disease or disorder is an ophthalmologic disease or disorder.