Treatment of abnormal cutaneous scarring

Abstract

The invention relates to the prevention and treatment of pathologic scars using APC or analogue thereof.

1 . A method for inducing the expression or production of TGF-β3 by a skin cell including the step of contacting a skin cell with APC or analogue thereof; thereby inducing the expression or production of TGF-β3 by the skin cell. 
     
     
         2 . The method of  claim 1  wherein the skin cell constitutively produces TGF-β3 and TGF-β1 and the contact of the skin cell with the APC or analogue thereof enhances the constitutive expression or production of TGF-β3 by the skin cell. 
     
     
         3 . The method of  claim 1  or  claim 2  wherein the contact of the skin cell with the APC or analogue thereof does not enhance the constitutive expression or production of TGF-β1 by the skin cell. 
     
     
         4 . The method of any one of the preceding claims wherein the expression or production of TGF-33 is enhanced by about 100 to 500% in treated fibroblasts or about 5 to 50% in treated keratinocytes, relative to the constitutive expression or production of TGF-β3. 
     
     
         5 . The method of any one of the preceding claims wherein the skin cell is fibroblast, myofbroblast, endothelial cell or keratinocyte. 
     
     
         6 . The method of any one of the preceding claims wherein the skin cell is provided in a composition including one or more of a fibroblast, myofibroblast, endothelial cell and keratinocyte. 
     
     
         7 . A method for inhibiting or preventing the formation of a pathologic scar in an individual including the steps of:
 providing an individual having a site of tissue injury undergoing wound repair;   contacting the site of tissue injury with APC or analogue thereof;   thereby inhibiting or preventing the formation of a pathologic scar in the individual.   
     
     
         8 . The method of  claim 7  wherein the individual is one at risk for the formation of a pathological scar. 
     
     
         9 . The method of  claim 7 , including the further steps of:
 determining whether an individual is at risk for formation of a pathologic scar;   selecting an individual determined to be at risk for formation of a pathologic scar for treatment in the method.   
     
     
         10 . The method of any one of  claims 6  to  9  wherein the injury is a burn. 
     
     
         11 . A method for minimising or reducing the appearance of a pathologic scar in an individual including the steps of:
 providing an individual having a pathologic scar;   contacting the pathologic scar with APC or analogue thereof;   thereby reducing the appearance of a pathologic scar in the individual.   
     
     
         12 . The method of  claim 11  wherein the scar is a hypertrophic scar. 
     
     
         13 . The method of  claim 11  or  12  wherein the scar arises from a burn. 
     
     
         14 . The method of any one of  claims 7  to  13  wherein the APC or analogue thereof is provided topically or in the form of an injectable composition for use in the method. 
     
     
         15 . The method of any one of  claims 7  to  14  wherein the APC or analogue thereof is provided in an amount of from 0.1 μg to 5000 μg of APC per cm 2  of the region of skin to which the APC is applied, or from 1 μg to 2000 μg of APC per cm 2  of the region of skin to which the APC is applied, or from 10 μg to 1000 μg of APC per cm 2  of the region of skin to which the APC is applied, or from 10 μg to 500 μg of APC per cm 2  of the region of skin to which the APC is applied. 
     
     
         16 . The method of any one of  claims 7  to  15  wherein the APC or analogue thereof is provided at least once per day. 
     
     
         17 . The method of any one of  claims 7  to  10 ,  14  and  15  wherein the APC or analogue thereof is provided for a period of no more than about 4 to 5 weeks from the time of the injury. 
     
     
         18 . The method of any one of  claims 11  to  15  wherein the APC or analogue thereof is provided for a period of about 4 to 20 weeks. 
     
     
         19 . The method of any one of the preceding claims wherein the APC analogue is 3K3A-APC.