Therapeutic use of activators of zinc finger protein GL13

• US 9,540,648 B2
• Filed: 01/25/2013
• Issued: 01/10/2017
• Est. Priority Date: 01/26/2012
• Status: Active Grant

• Current Assignee: Universitã¤T Leipzig
• Original Assignee: Universitã¤T Leipzig
• Inventors: Gebhardt, Rolf
• Primary Examiner(s): HOWARD, ZACHARY C
• Application Number:
  US14/374,887
• Publication Number:
  US 20140336111A1
• Time in Patent Office: 1,446 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A23L 33/13 Nucleic acids or derivatives thereof A23L33/145 takes precedence
• CPC Class Codes: A23V 2002/00 Food compositions, function of food ingredients or processes for food or foodstuffs
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/381 having five-membered rings
• CPC Class Codes: A61K 31/4436 containing a heterocyclic ring having sulfur as a ring hetero atom
• CPC Class Codes: A61K 38/1709 from mammals
• CPC Class Codes: A61K 38/22 Hormones derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin A61K38/33, e.g. corticotropin A61K38/35
• CPC Class Codes: A61K 38/2264 Obesity-gene products, e.g. leptin
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: C12N 15/1135 against oncogenes or tumor suppressor genes
• CPC Class Codes: C12N 15/1136 against growth factors, growth regulators, cytokines, lymphokines or hormones
• CPC Class Codes: C12N 15/1138 against receptors or cell surface proteins
• CPC Class Codes: C12N 2310/11 Antisense
• CPC Class Codes: C12N 2310/14 interfering N.A.
• CPC Class Codes: C12N 2320/30 Special therapeutic applications

Abstract

The present invention relates to the therapeutic use of activators of the zinc finger protein GLI3 in diseases that are associated with reduced Hedgehog signaling in hepatocytes, in particular Polycystic ovary syndrome, Steatosis hepatis, Steatohepatitis and/or Adipositas. The invention further relates to methods of treating an individual with said activator, a pharmaceutical composition comprising said activator and the use of said activator as food supplement.

Claims

1. A method for treating or preventing a disease associated with reduced Hedgehog signaling in hepatocytes, including the step of administering to an individual in need thereof a therapeutically effective amount of an activator of the Hedgehog signaling pathway selected from the group consisting of:

Sonic hedgehog (Shh), Indian hedgehog (Ihh), Desert hedgehog (Dhh), Smoothened agonist (SAG);

compounds according to the following formula (1)

2. The method of claim 1, wherein the activator of the Hedgehog signaling pathway is administered to at least one hepatocyte of said individual.

3. The method according to claim 1, wherein the disease is associated with imbalanced liver lipid metabolism and/or increased fat deposits.

4. The method of claim 1, wherein the disease is selected from the group consisting of

polycystic ovary syndrome,

fatty liver disease,

non-alcoholic fatty liver disease,

adiposity, and

combinations thereof.

5. The method of claim 4, wherein the non-alcoholic fatty liver disease is non-alcoholic Steatosis hepatis or non-alcoholic Steatohepatitis.

6. The method of claim 4, wherein the fatty liver disease is Steatosis hepatis or Steatohepatitis.

7. The method of claim 1, for reducing visceral fat deposition or prevention of visceral fat deposition.

8. The method of claim 1, wherein the activator of the Hedgehog signaling pathway is SAG.

9. A method for activating Hedgehog signaling in hepatocytes comprising administration to an individual in need thereof an activator of the zinc finger protein GLI3 selected from the group consisting of:

Sonic hedgehog (Shh), Indian hedgehog (Ihh), Desert hedgehog (Dhh), Smoothened agonist (SAG);

compounds according to the following formula (1)