Process of inhibiting cell death in injured cartilage

Abstract

Processes for inhibiting apoptotic cell death and glycosaminoglycan release from injured cartilage is provided. Inhibition is accomplished using caspase inhibitors.

1 . A process of inhibiting apoptotic cell death in cartilage following traumatic mechanical injury of the cartilage of a human patient, comprising (a) identifying a human patient having a traumatic mechanical injury to cartilage; and (b) administering to the patient a non-fluoromethylketone based caspase inhibitor to specifically inhibit the activity of cysteine-aspartate-specific proteases in the injured cartilage, thereby inhibiting apoptotic cell death in cartilage of the patient. 
     
     
         2 . The process of  claim 1 , wherein the caspase inhibitor is administered to the patient within seven days of the injury. 
     
     
         3 . The process of  claim 1 , wherein the caspase inhibitor is administered in an amount that is sufficient to achieve a concentration of from about 20 μM to about 250 μM in an interstitial fluid which perfuses the injured cartilage. 
     
     
         4 . The process of  claim 1 , wherein the traumatic mechanical injury of the cartilage is blunt traumatic mechanical injury. 
     
     
         5 . The process of  claim 1 , wherein the traumatic mechanical injury of the cartilage is external traumatic mechanical injury. 
     
     
         6 . The process of  claim 1 , wherein the cartilage is articular cartilage. 
     
     
         7 . A process of inhibiting glycosaminoglycan release from cartilage following mechanical injury of the cartilage of a human patient, comprising inhibiting apoptotic cell death in the injured cartilage by inhibiting the activity of cysteine-aspartate-specific proteases in the injured cartilage. 
     
     
         8 . The process of  claim 7 , wherein the activity of cysteine-aspartate-specific proteases is inhibited by contacting the cartilage with a caspase inhibitor. 
     
     
         9 . The process of  claim 8 , wherein the caspase inhibitor is a fluoromethylketone caspase inhibitor. 
     
     
         10 . The process of  claim 8 , wherein the caspase inhibitor is a broad spectrum caspase inhibitor. 
     
     
         11 . The process of  claim 8 , wherein the caspase inhibitor is administered to the patient within seven days of the injury. 
     
     
         12 . The process of  claim 8 , wherein the caspase inhibitor is administered in an amount that is sufficient to achieve a concentration of from about 20 μM to about 250 μM in an interstitial fluid which perfuses the injured cartilage. 
     
     
         13 . The process of  claim 7 , wherein the traumatic mechanical injury of the cartilage is blunt traumatic mechanical injury. 
     
     
         14 . The process of  claim 7 , wherein the traumatic mechanical injury of the cartilage is external traumatic mechanical injury. 
     
     
         15 . The process of  claim 7 , wherein the cartilage is articular cartilage.