Connective Tissue Growth Factor Fragments and Methods and Uses Thereof

Abstract

The present invention is directed to CTGF fragments comprising at least exon 2 or exon 3 of CTGF and having the ability to induce extracellular matrix synthesis, in particular, collagen synthesis and myofibroblast differentiation. The present invention is further directed to methods using said CTGF fragments to identify compositions which modulate the activity of said CTGF fragments and to the compositions so identified. The invention also relates to methods of treating CTGF-associated disorders and diseases associated with the overproduction of the extracellular matrix.

1 . An antisense molecule that binds to a nucleic acid sequence encoding a fragment of CTGF polypeptide, wherein the fragment of CTGF has the ability to induce extracellular matrix and/or collagen synthesis. 
     
     
         2 . The antisense molecule of  claim 1 , wherein the fragment of CTGF comprises an amino acid sequence selected from the group consisting of:
 (a) residue 24 through 95 of SEQ ID NO:4;   (b) residue 96 through 180 of SEQ ID NO:4; and   (c) residue 24 through 180 of SEQ ID NO:4.   
     
     
         3 . A method for treating a CTGF-associated disease or disorder comprising administering to a subject in need the antisense molecule of  claim 1 . 
     
     
         4 . The method of  claim 3 , wherein the disease or disorder is a fibroproliferative disease/disorder. 
     
     
         5 . The method of  claim 3 , wherein the disease or disorder is selected from the group consisting of kidney fibrosis, scleroderma, pulmonary fibrosis, liver fibrosis, arthritis, hypertropic scarring, atherosclerosis, diabetic nephropathy and retinopathy, hypertension, kidney disorders, angiogenesis-related disorders, skin fibrotic disorders, and cardiovascular disorders.