Moesin modulators and uses thereof

Abstract

The present application provides compositions and methods useful for treating and diagnosing diseases and disorders associated with moesin activation.

What is claimed is: 
     
         1 . A method for treating a disorder or pathological condition associated with abnormal moesin activation in a subject, comprising
 administering to the subject a composition comprising an effective amount of a moesin inhibitor capable of inhibiting the activation of human moesin.   
     
     
         2 . The method of  claim 1 , wherein the disorder or pathological condition is associated with respiratory system or fibrosis of organs. 
     
     
         3 . The method of  claim 2 , wherein the fibrosis of organs is pulmonary fibrosis, cystic fibrosis, cirrhosis, endomyocardial fibrosis, myelofibrosis, retroperitoneal fibrosis, Crohn's Disease, Keloid, systemic sclerosis or progressive massive fibrosis. 
     
     
         4 . The method of  claim 2 , wherein the disorder or pathological condition is pulmonary artery hypertension. 
     
     
         5 . The method of  claim 1 , wherein the moesin inhibitor is an isolated antibody that binds the C-terminal tail domain of human moesin (SEQ ID NO:1). 
     
     
         6 . The method of  claim 5 , wherein the isolated antibody blocks the phosphorylation site Threonine 558 of human moesin. 
     
     
         7 . The method of  claim 1 , wherein the moesin inhibitor comprises a truncated moesin fragment having at least ten contiguous amino acid residues of the C-terminal tail domain of human moesin (SEQ ID NO:1). 
     
     
         8 . The method of  claim 7 , wherein the truncated moesin fragment comprises the phosphorylation site Threonine 558. 
     
     
         9 . The method of  claim 8 , wherein the truncated moesin fragment is capable of competing for the phosphorylation of Threonine 558 with full length human moesin. 
     
     
         10 . The method of  claim 9 , wherein the truncated moesin fragment comprises at least ten contiguous amino acid residues of the sequence GRDKYKTLRQIRQ (SEQ ID NO:2). 
     
     
         11 . The method of  claim 1 , wherein the moesin inhibitor inhibits proliferation of epithelial or endothelial cells. 
     
     
         12 . The method of  claim 1 , wherein the moesin inhibitor promotes apoptosis of epithelial or endothelial cells. 
     
     
         13 . The method of  claim 1 , wherein the composition further comprises a carrier. 
     
     
         14 . The method of  claim 1 , wherein the composition further comprises an effective amount of a second therapeutic agent suitable for combination use with the moesin inhibitor. 
     
     
         15 . The method of  claim 14 , wherein the second therapeutic agent is a cytokine. 
     
     
         16 . The method of  claim 15 , wherein the cytokine is a proinflammatory cytokine. 
     
     
         17 . The method of  claim 16 , wherein the proinflammatory cytokine is TNF-alpha, TNF-beta, IL-1 or IL-6.