Biglycan variant polypeptides and methods of use

Abstract

The invention provides compositions and methods for treating, preventing, and diagnosing diseases or conditions associated with an abnormal level or activity of biglycan; disorders associated with an unstable cytoplasmic membrane, due, e.g., to an unstable dystrophin associated protein complex (DAPC); disorders associated with abnormal synapses or neuromuscular junctions, including those resulting from an abnormal MuSK activation or acetylcholine receptor (AChR) aggregation. Examples of diseases include Amyotrophic Lateral Sclerosis (ALS), as well as muscular dystrophies, such as Duchenne's Muscular Dystrophy, Becker's Muscular Dystrophy, neuromuscular disorders and neurological disorders.

What is claimed is: 
     
         1 . A method for preventing or treating a disorder in a subject, comprising, administering to the subject a composition comprising an isolated biglycan variant polypeptide lacking glycosaminoglycan side chains, wherein the variant polypeptide potentiates agrin-induced AChR clustering. 
     
     
         2 . The method of  claim 1 , wherein the variant polypeptide is the M form of the polypeptide. 
     
     
         3 . The method of  claim 1 , wherein the disorder is a muscular, neuromuscular or neurological disorder. 
     
     
         4 . The method of  claim 3 , wherein the disorder is associated with an abnormal dystrophin-associated protein complex (DAPC). 
     
     
         5 . The method of  claim 3 , wherein the disorder is characterized by an abnormal neuromuscular junction or synapse in the subject. 
     
     
         6 . The method of  claim 3 , wherein the disorder is muscular dystrophy. 
     
     
         7 . The method of  claim 6 , wherein the disorder is selected from the group consisting of Duchenne's Muscular Dystrophy, Becker's Muscular Dystrophy, Congenital Muscular Dystrophy, Lamb-girdle Muscular Dystrophy, and mytonic dystrophy. 
     
     
         8 . The method of  claim 3 , wherein the disorder is low bone mass, osteoarthritis, or ectopic bone formation. 
     
     
         9 . The method of  claim 3 , wherein the disorder is Amyotrophic Lateral Sclerosis. 
     
     
         10 . The method of  claim 3 , wherein the disorder is congestive heart failure.