Methods and compositions for treatment of cartilage damage and arthritis

Abstract

The invention provides methods and compositions for the treatment of cartilage damage or arthritis.

1 . A method of treating arthritis or cartilage damage in a human subject, the method comprising administering to a joint of the human subject an intra-articular dose of about 0.2-200 mg of a polypeptide comprising an amino acid sequence having at least 95% sequence identity to an amino acid sequence listed in Table 1, wherein the polypeptide comprises an amino acid that is a polar amino acid other than K or R at position 423, as determined with reference to SEQ ID NO:1, and the polypeptide has chondrogenic activity. 
     
     
         2 . The method of claim of 1, wherein the amino acid corresponding to position 423 of SEQ ID NO: 1 in the polypeptide is Q or S or deleted. 
     
     
         3 . The method of  claim 1 , wherein the polypeptide comprises an amino acid sequence listed in Table 1. 
     
     
         4 . The method of  claim 1 , wherein the polypeptide comprises SEQ ID NO: 17. 
     
     
         5 . The method of  claim 1 , wherein the intra-articular dose is about 0.2-60 mg. 
     
     
         6 . The method of  claim 5 , wherein the intra-articular dose is about 20 mg. The method of  claim 5 , wherein the intra-articular dose is about 40 mg. 
     
     
         8 . The method of  claim 5 , wherein the intra-articular dose is about 60 mg. 
     
     
         9 . The method of  claim 1 , wherein the polypeptide is administered to the joint of the human subject in a single injection. 
     
     
         10 . The method of  claim 1 , wherein the polypeptide is administered to the joint of the human subject monthly for a time period sufficient to treat the arthritis or cartilage damage. 
     
     
         11 . The method of  claim 1 , wherein administering the polypeptide occurs in conjunction with any one of bone marrow stimulation, cartilage replacement, autologous chondrocyte implantation (ACI), or matrix-induced autologous chondrocyte implantation (MACI). 
     
     
         12 . The method of  claim 1 , wherein administering the polypeptide occurs in conjunction with autologous chondrocyte implantation (ACI). 
     
     
         13 . The method of  claim 1 , wherein the human subject has osteoarthritis, trauma arthritis, or autoimmune arthritis. 
     
     
         14 . The method of  claim 1 , wherein the human subject has cartilage damage.