Methods for modifying progression of osteoarthritis

Abstract

Methods for modifying progression of osteoarthritis by local administration of a clostridial derivative, such as a botulinum toxin, to an arthritis-affected site are disclosed herein.

We claim: 
     
         1 . A method for treating osteoarthritis in a patient in need thereof, the method comprising locally administering a therapeutically effective amount of a clostridial derivative to an osteoarthritis-affected site of the patient, thereby treating osteoarthritis in the patient; wherein the administering reduces the levels of at least one cartilage-degrading agent, increasing the levels of at least one cartilage-forming component, or both. 
     
     
         2 . The method of  claim 1 , wherein the at least one cartilage-degrading agent is selected from the group consisting of metalloproteinases, cysteine proteinases, aspartate proteinases, serine proteinases, or combinations thereof. 
     
     
         3 . The method of  claim 1 , wherein the at least one cartilage-forming component is selected from the group consisting of aggrecan, proteoglycans, collagens, hyaluronan, or combinations thereof. 
     
     
         4 . The method of  claim 1 , wherein the osteoarthritis-affected site is selected from the group consisting of a knee joint, a hip joint, a hand joint, a shoulder joint, an ankle joint, a foot joint, an elbow joint, a wrist joint, a sacroiliac joint, a spine joint, or combinations thereof. 
     
     
         5 . The method of  claim 1 , wherein the administering is by intra-articular injection into a joint space. 
     
     
         6 . The method of  claim 1 , wherein the clostridial derivative is selected from the group consisting of botulinum toxin types A, B, C 1 , D, E, F and G. 
     
     
         7 . The method of  claim 7 , wherein the botulinum toxin is type A and wherein the therapeutically effective amount is from about 2 units to about 800 units. 
     
     
         8 . A method for delaying progression of osteoarthritis or repairing cartilage defect in a patient in need thereof, the method comprising modifying the levels of at least one cartilage-forming component, one cartilage-degrading agent, or both, by locally administering a therapeutically effective amount of a clostridial derivative to an osteoarthritis-affected site of the patient, thereby delaying progression of osteoarthritis or repairing cartilage defect in the patient. 
     
     
         9 . The method of  claim 8 , wherein the at least one cartilage-forming component is selected from the group consisting of aggrecan, proteoglycans, collagens, hyaluronan, or combinations thereof. 
     
     
         10 . The method of  claim 8 , wherein the at least one cartilage-degrading agent is a proteinase. 
     
     
         11 . The method of  claim 10 , wherein the proteinase is selected from the group consisting of metalloproteinases, cysteine proteinases, aspartate proteinases, serine proteinases, or combinations thereof. 
     
     
         12 . The method of  claim 10 , wherein the at least one cartilage-degrading agent is matrix metalloproteinase-1. 
     
     
         13 . The method of  claim 8 , wherein the osteoarthritis-affected site is selected from the group consisting of a knee joint, a hip joint, a hand joint, a shoulder joint, an ankle joint, a foot joint, an elbow joint, a wrist joint, a sacroiliac joint, a spine joint, or combinations thereof. 
     
     
         14 . The method of  claim 8 , wherein the clostridial derivative is selected from the group consisting of botulinum toxin types A, B, C 1 , D, E, F and G. 
     
     
         15 . A method for reversing cartilage breakdown in a patient suffering from osteoarthritis, the method comprising modifying the levels and/or activities of at least one agent associated with osteoarthritis-mediated cartilage breakdown, by locally administering a therapeutically effective amount of a clostridial derivative to an osteoarthritis-affected site of the patient, thereby reversing cartilage breakdown in the patient. 
     
     
         16 . The method of  claim 15 , wherein the at least one agent associated with osteoarthritis-medicated cartilage breakdown comprises a cartilage-degrading agent, a cartilage-forming component, or mixtures thereof. 
     
     
         17 . The method of  claim 16 , wherein the cartilage-degrading agent is selected from a group consisted of metalloproteinases, cysteine proteinases, aspartate proteinases, serine proteinases, or combinations thereof. 
     
     
         18 . The method of  claim 16 , wherein the cartilage-forming component is selected from the group consisting of aggrecan, proteoglycans, collagens, hyaluronan, or combinations thereof. 
     
     
         19 . The method of  claim 15 , wherein the osteoarthritis-affected site is selected from the group consisting of a knee joint, a hip joint, a hand joint, a shoulder joint, an ankle joint, a foot joint, an elbow joint, a wrist joint, a sacroiliac joint, a spine joint, or combinations thereof. 
     
     
         20 . The method of  claim 15 , wherein the clostridial derivative is selected from the group consisting of botulinum toxin types A, B, C 1 , D, E, F and G.