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

Patent metadata

Field	Value
Publication number	US-2016168565-A1
Application number	US-201414909626-A
Country	US
Kind code	A1
Filing date	Jul 30, 2014
Priority date	Aug 5, 2013
Publication date	Jun 16, 2016
Grant date	—

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.

First claim

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, FOXS1, CREB5, IRF7, POU2F2, STAT4 and TCF4, preferentially TCF4, FOXS1, STAT4; and/or an agent that enhances the activity of at least one gene selected from the group consisting of MAF, MEOX2 and SIX2.

2 . A 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 . A 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 . A method according to claim 1 wherein said agent is an inhibitor or enhancer of protein function.

5 . A 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 . A 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 . A 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 . A method according to claim 1 wherein the therapeutic compound is for topical application.

9 . A 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, FOXS1, CREB5, IRF7, POU2F2, STAT4, TCF4, preferentially TCF4, FOXS1, STAT4 and/or an agent that enhances the activity of at least one gene selected from the group consisting of MAF, MEOX2, 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 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, FOXS1, CREB5, IRF7, POU2F2, STAT4, TCF4, preferentially TCF4, FOXS1, STAT4 and/or an agent that enhances the activity of at least one gene selected from the group consisting of MAF, MEOX2, SIX2 and b) at least one further therapeutic.

15 . 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, FOXS1, CREB5, IRF7, POU2F2, STAT4, TCF4, preferentially TCF4, FOXS1, STAT4 and/or an agent that enhances the activity of at least one gene selected from the group consisting of MAF, MEOX2, SIX2, wherein said agent modulates fibroblast and myofibroblast differentiation and/or activity.

16 . 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.

Assignees

• Centre Nat Rech Scient
• Inserm Inst Nat De La Santé Et De La Rech Médicale
• Urgo Rech Innovation Et Développement
• Univ Paris Diderot Paris 7
• Ecole Normale Superieure
• Ct Nat De La Rech Scienctifique Cnrs

Inventors

• Dugast-Darzacq Claire
• Noizet Maite
• Darzacq Xavier

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P17/02

  for treating wounds, ulcers, burns, scars, keloids, or the like · CPC title

• C12N15/113 Primary

  Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; {Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing (when used in plants C12N15/8218)} · CPC title

• C12N2320/12

  in functional genomics, i.e. for the determination of gene function · CPC title

• C12N2320/30

  Special therapeutic applications · CPC title