Molecular targets for the prevention and/or treatment of fibrosis, hypertrophic scars or keloids

Abstract

The present invention relates to a therapeutic compound comprising: an agent that inhibits the activity of at least one gene selected from the group consisting of HIC1, FOXS1, CREB5, IRF7, POU2F2, STAT4, TCF4, and/or an agent that enhances the activity of at least one gene selected from the group consisting of MAF, MEOX2, SIX2.

1 . A method for preventing and/or treating fibrosis, hypertrophic scar or keloid in a subject in need thereof, comprising administering to said subject a therapeutic compound comprising :
 an agent that inhibits the activity of at least one gene selected from the group consisting of HIC1, CREB5, IRF7, POU2F2, and STAT4;   
       and/or
 an agent that enhances the activity of at least one gene selected from the group consisting of MEOX2 and SIX2. 
 
     
     
         2 . The method according to  claim 1  further comprising:
 an agent that inhibits the activity of at least one gene selected from the group consisting of E2F1, EGR2, GLI1, JUN, MYC, SMAD3, SMAD4 and SOX9, SRF, preferentially EGR2, SOX9 
 
       and/or
 an agent that enhances the activity of at least one gene selected from the group consisting of ETS1 and PPARG. 
 
     
     
         3 . The method according to  claim 1  wherein said agent is selected from the group consisting of: anti-sense DNA or RNA, siRNA, shRNA, cDNA, TALENS or ribozymes, either naked or in the form of plasmid or viral vectors. 
     
     
         4 . The method according to  claim 1  wherein said agent is an inhibitor or enhancer of protein function. 
     
     
         5 . The method according to  claim 4  wherein said agent is selected from the group consisting of: a binding agent that binds, either reversibly or irreversibly, to inhibit protein function such as an antibody or a synthetic antagonist; or an agent that works upstream or downstream of the protein signaling mechanism to inhibit protein function. 
     
     
         6 . The method according to  claim 1  wherein it is for treating mammalian fibrosis, hypertrophic scars or keloid or tissue susceptible of developing fibrosis, hypertrophic scar or keloid. 
     
     
         7 . The method according to  claim 1  wherein it is for treating human fibrosis, hypertrophic scars or keloid or tissue susceptible of developing fibrosis, hypertrophic scar or keloid. 
     
     
         8 . The method according to  claim 1  wherein the therapeutic compound is for topical application. 
     
     
         9 . The method according to  claim 1  wherein the therapeutic compound is for application to a dressing or impregnation of a dressing. 
     
     
         10 . A pharmaceutical composition comprising a therapeutic compound according to  claim 1  together with a pharmaceutically acceptable carrier. 
     
     
         11 . A method for preparing a pharmaceutical composition according to  claim 10  comprising bringing said therapeutic compound in conjunction or association with a pharmaceutically or veterinary acceptable carrier or vehicle. 
     
     
         12 . A method for treating a mammalian fibrosis, hypertrophic scar or keloid or tissue susceptible of developing fibrosis, hypertrophic scar or keloid, wherein said method comprises administering to said fibrosis, hypertrophic scar or keloid or tissue susceptible of developing fibrosis, hypertrophic scar or keloid, a therapeutic compound comprising:
 an agent that inhibits the activity of at least one gene selected from the group consisting of HIC1, CREB5, IRF7, POU2F2, and STAT4,   
       and/or
 an agent that enhances the activity of at least one gene selected from the group consisting of MEOX2 and SIX2. 
 
     
     
         13 . A kit for treating a fibrosis, hypertrophic scar or keloid or tissue susceptible of developing fibrosis, hypertrophic scar or keloid wherein said kit comprises:
 (a) at least one therapeutic compound according to  claim 1  and   (b) at least one dressing for applying to said fibrosis, hypertrophic scar or keloid or tissue susceptible of developing fibrosis, hypertrophic scar or keloid.   
     
     
         14 . A kit for treating a fibrosis, hypertrophic scar or keloid or tissue susceptible of developing fibrosis, hypertrophic scar or keloid wherein said kit comprises:
 (a) a composition according to  claim 10  and   (b) at least one dressing for applying to said fibrosis, hypertrophic scar or keloid or tissue susceptible of developing fibrosis, hypertrophic scar or keloid.   
     
     
         15 . A combination therapy for treating a fibrosis, hypertrophic scar or keloid or tissue susceptible of developing fibrosis, hypertrophic scar or keloid comprising:
 (a) an agent that inhibits the activity of at least one gene selected from the group consisting of HIC1, CREB5, IRF7, POU2F2, STAT4,   
       and/or
 an agent that enhances the activity of at least one gene selected from the group consisting of MEOX2 and SIX2 
 
       and
 b) at least one further therapeutic. 
 
     
     
         16 . A method for treating a fibrosis, hypertrophic scar or keloid or tissue susceptible of developing fibrosis, hypertrophic scar or keloid, comprising administering:
 an agent that inhibits the activity of at least one gene selected from the group consisting of HIC1, CREB5, IRF7, POU2F2, STAT4,   
       and/or
 an agent that enhances the activity of at least one gene selected from the group consisting of MEOX2 and SIX2, 
 
       wherein said agent modulates fibroblast and myofibroblast differentiation and/or activity.