Method for treating adamts-5-associated disease

Abstract

The present invention relates to methods of treating ADAMTS-5-associated diseases and particularly osteoarthritis comprising administering an agent capable of modulating ADMATS-5 activity to a subject afflicted with the disease. The agent is preferably a biaryl sulfonamide compound. The invention is based, in part, on the discovery that transgenic animals that do not express functional ADAMTS-5 show a reduction in the degree of osteoarthritis after the induction of osteoarthritis as compared to WT animals. Furthermore, the ADAMTS-5 transgenic animals have reduced aggrecanase activity in articular tissue as compared to WT animals. These animals are good models for ADAMTS-5-associated diseases, and for screening of drugs useful in the treatment and/or prevention of these diseases. There are no other animal models in which the deletion of the activity of a single gene is capable of abrogating the course of osteoarthritis. Accordingly, these animals also show that osteoarthritis can be prevented and/or treated by administering to a subject an ADAMTS-5 inhibitory agent and particularly an agent capable of inhibiting the aggrecanase activity of ADAMTS-5.

1 . A method for treating osteoarthritis, comprising administering to a subject in need thereof a therapeutically effective amount of an agent which inhibits ADAMTS-5, wherein the agent is an anti-ADAMTS-5 antibody. 
     
     
         2 - 17 . (canceled) 
     
     
         18 . A method for identifying a potential agent useful for the treatment of an ADAMTS-5-associated disease comprising contacting ADAMTS-5 with the potential agent and measuring the activity of ADAMTS-5 in the presence of the potential agent, wherein a reduction in activity is indicative that the potential agent is useful for the treatment of the disease. 
     
     
         19 . The method of  claim 18 , wherein the activity is selected from the group consisting of metalloproteinase activity and aggrecanase activity. 
     
     
         20 . The method of  claim 18  or  19 , wherein the ADAMTS-5 is in a cell and the activity is measured in the cell. 
     
     
         21 . The method of  claim 20 , further comprising contacting a cell lacking ADAMTS-5 with the potential agent, measuring the activity in the cell lacking ADAMTS-5 and comparing the activity to the activity of the cell having ADAMTS-5. 
     
     
         22 . The method of  claim 18 , wherein the ADAMTS-5-associated disease is selected from the group consisting of osteoarthritis, cancer, asthma, chronic obstructive pulmonary disease (“COPD”), atherosclerosis, age-related macular degeneration, myocardial infarction, corneal ulceration and other ocular surface diseases, hepatitis, aortic aneurysms, tendonitis, central nervous system diseases, abnormal wound healing, angiogenesis, restenosis, cirrhosis, multiple sclerosis, glomerulonephritis, graft versus host disease, diabetes, inflammatory bowel disease, shock, invertebral disc degeneration, stroke, osteopenia, and periodontal disease. 
     
     
         23 . The method of  claim 18 , wherein the ADAMTS-5-associated disease is osteoarthritis. 
     
     
         24 - 37 . (canceled) 
     
     
         38 . The method of  claim 18 , wherein the agent is an anti-ADAMTS-5 antibody. 
     
     
         39 . The method of  claim 1  or  38 , wherein the antibody has metalloprotese inhibitory activity. 
     
     
         40 . The method of  claim 39 , wherein the antibody has aggrecanase inhibitory activity.