Methods for treating tweak-related conditions

Abstract

The present invention provides methods and agents for the treatment of TWEAK-related conditions, including cardiac, liver, kidney, lung, adipose, skeletal, muscle, neuronal, bone and cartilage conditions. The invention also provides methods for identifying TWEAK agonists or antagonists for the treatment of TWEAK-related conditions. Additionally, the invention provides transgenic animals that express an exogenous DNA encoding a TWEAK polypeptide, or fragments, analogs, or muteins thereof, and methods for using such animals to identify TWEAK agonists or antagonists. The invention further provides methods for diagnosing a disease based on TWEAK expression. The invention also provides methods for affecting cellular differentiation of progenitor cells using TWEAK polypeptides, agonists, or antagonists.

1 . A method for treating glomerular disease in a human subject comprising the step of administering to the subject a therapeutically effective amount of a TWEAK antagonist selected from the group consisting of: (a) an antibody that binds human TWEAK (an anti-TWEAK antibody) or antigen-binding fragment thereof; (b) an antibody that binds human Fn14; and (c) a soluble human TWEAK receptor polypeptide. 
     
     
         2 . The method of  claim 1 , wherein the glomerular disease is selected from glomerulonephritis and glomerular nephropathy. 
     
     
         3 . The method of  claim 1 , wherein the glomerular disease is kidney fibrosis. 
     
     
         4 . The method of  claim 1 , wherein the glomerular disease is caused by an immunologic disorder, vascular disorder, diabetes mellitus, or Fabry disorder. 
     
     
         5 . The method of  claim 4 , wherein the immunologic disorder is systemic lupus erythematosus (SLE). 
     
     
         6 . The method of  claim 1 , wherein the antibody is human or humanized. 
     
     
         7 . The method of  claim 1 , wherein the antibody is monoclonal or chimeric. 
     
     
         8 . The method of  claim 1 , wherein the antibody is full length. 
     
     
         9 . The method of  claim 1 , wherein the antibody is an antigen-binding fragment. 
     
     
         10 . The method of  claim 1 , wherein the TWEAK antagonist is administered to the subject via a route selected from the group consisting of: injection, transmucosal, oral, inhalation, ocular, rectal, stent implantation, topical, parenteral, long acting implantation, sustained release, and aural routes. 
     
     
         11 . The method of  claim 1 , wherein said TWEAK antagonist is in a delivery formulation selected from the group consisting of: tablets, pills, liposomes, granules, spheres, dragees, capsules, liquids, gels, syrups, slurries, suspensions, stent coatings and sustained-release formulations. 
     
     
         12 . A method for treating fibrosis in a human subject comprising the step of administering to the subject a therapeutically effective amount of a TWEAK antagonist selected from the group consisting of: (a) an antibody that binds human TWEAK (an anti-TWEAK antibody) or antigen-binding fragment thereof; (b) an antibody that binds human Fn14; and (c) a soluble human TWEAK receptor polypeptide. 
     
     
         13 . The method of  claim 12 , wherein the fibrosis is selected from kidney fibrosis, liver fibrosis, or cardiac fibrosis. 
     
     
         14 . A method for treating heart disease characterized by fn14 expression in a human subject comprising the step of administering to the subject a therapeutically effective amount of a TWEAK antagonist selected from the group consisting of: (a) an antibody that binds human TWEAK (an anti-TWEAK antibody) or antigen-binding fragment thereof; (b) an antibody that binds human Fn14; and (c) a soluble human TWEAK receptor polypeptide.