Molecular targets for the treatment of wounds, in particular chronic wounds

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 MAF, MEOX2, SIX2 and homologues thereof having at least 50% identity with said genes and/or an agent that enhances the activity of at least one gene selected from the group consisting of CREB5, E2F1, EGR2, HIC1, IRF7, JUN, MYC, SRF, STAT4, TCF4, FOXS1, GLI1, SOX9 and homologues thereof having at least 50% identity with said gene for use in the treatment of wounds, preferably chronic wounds.

1 .- 19 . (canceled) 
     
     
         20 . A method for treating wounds, preferably chronic wounds, 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 MEOX2, SIX2, and homologues thereof having at least 50% identity with said genes, and/or   an agent that enhances the activity of at least one gene selected from the group consisting of CREB5, E2F1, EGR2, HIC1, IRF7, JUN, MYC, SRF, STAT4, GLI1, preferentially EGR2, STAT4 and homologues thereof having at least 50% identity with said gene.   
     
     
         21 . The method according to  claim 20  further comprising:
 an agent that inhibits the activity of PPARG or homologues thereof having at least 50% identity with PPARG; and/or 
 an agent that enhances the activity of at least one gene selected from the group consisting of SMAD3, SMAD4 and homologues thereof having at least 50% identity with said genes. 
 
     
     
         22 . The method according to  claim 20  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. 
     
     
         23 . The method according to  claim 20  wherein said agent is an inhibitor or enhancer of protein function. 
     
     
         24 . The method according to  claim 23  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. 
     
     
         25 . The method according to  claim 23  wherein said agent inhibits the activity of MEOX2 or SIX2; or wherein said agent enhances the activity of GLI1. 
     
     
         26 . The method according to  claim 23  wherein said agent is an agonist of GLI1. 
     
     
         27 . The method according to  claim 23 , wherein said agent is Gant 61. 
     
     
         28 . The method according to  claim 20  wherein it is for treating mammalian wounds. 
     
     
         29 . The method according to  claim 20  wherein it is for treating chronic wounds chosen among: venous ulcers, diabetic ulcers, or pressure ulcers. 
     
     
         30 . The method according to  claim 20  wherein it is for treating human wounds. 
     
     
         31 . The method according to  claim 20  wherein the therapeutic compound is for topical application. 
     
     
         32 . The method according to  claim 20  wherein the therapeutic compound is for application to a medical device or impregnation of a medical device. 
     
     
         33 . A pharmaceutical composition comprising a therapeutic compound comprising:
 an agent that inhibits the activity of at least one gene selected from the group consisting of MEOX2, SIX2, and homologues thereof having at least 50% identity with said genes, and/or   an agent that enhances the activity of at least one gene selected from the group consisting of CREB5, E2F1, EGR2, HIC1, IRF7, JUN, MYC, SRF, STAT4, GLI1, preferentially EGR2, STAT4 and homologues thereof having at least 50% identity with said gene; and   a pharmaceutically acceptable carrier.   
     
     
         34 . A method for preparing a pharmaceutical composition according to  claim 33  comprising combining said therapeutic compound with a pharmaceutically or veterinary acceptable carrier or vehicle. 
     
     
         35 . The method according to  claim 20 , wherein the subject is mammalian. 
     
     
         36 . A kit for treating a wound, preferably a chronic wound, wherein said kit comprises:
 (a) at least one therapeutic compound comprising:
 an agent that inhibits the activity of at least one gene selected from the group consisting of MEOX2, SIX2, and homologues thereof having at least 50% identity with said genes, and/or 
 an agent that enhances the activity of at least one gene selected from the group consisting of CREB5, E2F1, EGR2, HIC1, IRF7, JUN, MYC, SRF, STAT4, GLI1, preferentially EGR2, STAT4 and homologues thereof having at least 50% identity with said gene; and 
   (b) at least one dressing for applying to said wound.   
     
     
         37 . A combination therapeutic for treating a wound, preferably a chronic wound, comprising:
 a) the pharmaceutical composition of  claim 33 ; and   b) at least one further therapeutic.   
     
     
         38 . The method according to  claim 20 , wherein said agent modulates fibroblast and myofibroblast differentiation and/or activity.