Sulfated-oxysterol and oxysterol sulfation by hydroxysterol sulfotransferase promote lipid homeostasis and liver proliferation

Patent metadata

Field	Value
Publication number	US-9480692-B2
Application number	US-201514689822-A
Country	US
Kind code	B2
Filing date	Apr 17, 2015
Priority date	Apr 6, 2011
Publication date	Nov 1, 2016
Grant date	Nov 1, 2016

Abstract

Methods and compositions for the prevention and treatment of liver damage or disease in a subject in need thereof are provided. The methods involve providing the sulfated oxysterol 25-hydroxycholesterol-3-sulfate (25HC3S) to the subject e.g. by 1) administering 25HC3S to the subject; or 2) overexpressing, in the subject, the hydroxysterol sulfotransferase enzyme SULT2B1b, which catalyzes the sulfation of 25-hydroxycholesterol (25HC) to form 25HC3S.

First claim

We claimed:

1. A method for promoting hepatocyte proliferation in a liver surgery subject, comprising:
identifying the liver surgery subject, wherein the liver surgery subject is in need of hepatocyte proliferation, and
elevating a level of 25-hydroxycholesterol-3-sulfate (25HC3S) in the liver surgery subject, during or after liver surgery, by
administering to the liver surgery subject a composition comprising
25HC3S and
a physiologically compatible carrier,

wherein the elevating promotes hepatocyte proliferation in the liver surgery subject.

2. The method of claim 1 , wherein the 25HC3S is administered in an amount ranging from 0.1mg/kg to 100mg/kg, based on body mass of the liver surgery subject.

3. The method of claim 1 , wherein the 25HC3S is administered in an amount ranging from 0.1mg/kg to 10mg/kg, based on body mass of the liver surgery subject.

4. The method of claim 1 , wherein the administration comprises at least one of oral administration, enteric administration, sublingual administration, transdermal administration, intravenous administration, peritoneal administration, parenteral administration, administration by injection, subcutaneous injection, and intramuscular injection.

5. The method of claim 1 , wherein the administration comprises oral administration.

6. A method for promoting liver tissue regeneration in a liver surgery subject, comprising:
identifying the liver surgery subject, wherein the liver surgery subject is in need of liver tissue regeneration, and
elevating a level of 25-hydroxycholesterol-3-sulfate (25HC3S) in the liver surgery subject, during or after liver surgery, by
administering to the liver surgery subject a composition comprising
25HC3S and
a physiologically compatible carrier,

wherein the elevating promotes liver tissue regeneration in the liver surgery subject.

7. The method of claim 6 , wherein the 25HC3S is administered in an amount ranging from 0.1mg/kg to 100mg/kg, based on body mass of the liver surgery subject.

8. The method of claim 6 , wherein the 25HC3S is administered in an amount ranging from 0.1mg/kg to 10mg/kg, based on body mass of the liver surgery subject.

9. The method of claim 6 , wherein the administration comprises at least one of oral administration, enteric administration, sublingual administration, transdermal administration, intravenous administration, peritoneal administration, parenteral administration, administration by injection, subcutaneous injection, and intramuscular injection.

10. The method of claim 6 , wherein the administration comprises oral administration.

11. The method of claim 1 , wherein the liver surgery is liver transplantation.

12. The method of claim 1 , wherein the liver surgery is a partial hepatectomy.

13. The method of claim 12 , wherein the partial hepatectomy removes damaged or diseased liver tissue.

14. The method of claim 12 , wherein the partial hepatectomy removes a cancerous tumor.

15. The method of claim 6 , wherein the liver surgery is liver transplantation.

16. The method of claim 6 , wherein the liver surgery is a partial hepatectomy.

17. The method of claim 16 , wherein the partial hepatectomy removes damaged or diseased liver tissue.

18. The method of claim 16 , wherein the partial hepatectomy removes a cancerous tumor.

19. The method of claim 1 , wherein the elevating occurs during liver surgery.

20. The method of claim 1 , wherein the elevating occurs after liver surgery.

21. The method of claim 6 , wherein the elevating occurs during liver surgery.

22. The method of claim 6 , wherein the elevating occurs after liver surgery.

Assignees

• Ren Shunlin
• Univ Virginia Commonwealth

Inventors

• Ren Shunlin

Classifications

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P3/06

  Antihyperlipidemics · CPC title

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title