Use of HMGB1 for protection against ischemia reperfusion injury

• US 7,829,097 B2
• Filed: 02/06/2007
• Issued: 11/09/2010
• Est. Priority Date: 02/06/2006
• Status: Active Grant

• Current Assignee: The Feinstein Institutes For Medical Research, University of Pittsburgh of The Commonwealth System of Higher Education
• Original Assignee: The Feinstein Institute for Medical Research (Northwell Health, Inc.), University of Pittsburgh of The Commonwealth System of Higher Education
• Inventors: Tsung, Allan, Billiar, Timothy R., Fink, Mitchell P., Tracey, Kevin J.
• Primary Examiner(s): SKELDING, ZACHARY S
• Application Number:
  US11/671,932
• Publication Number:
  US 20080004207A1
• Time in Patent Office: 1,372 Days
• Field of Search: None
• US Class Current: 424/185.1
• CPC Class Codes: A01N 1/02 Preservation of living parts
• CPC Class Codes: A01N 1/0226 Physiologically active agents, i.e. substances affecting physiological processes of cells and tissue to be preserved, e.g. anti-oxidants or nutrients
• CPC Class Codes: A61K 38/17 from animals; from humans enzyme inhibitors A61K38/005
• CPC Class Codes: A61P 37/02 Immunomodulators
• CPC Class Codes: A61P 9/10 for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Abstract

Methods and compositions are disclosed for protecting an organ or tissue from inflammation and organ injury following ischemia, reperfusion, and trauma through the administration of an HMGB1 protein within a time period sufficient to protect the organ or tissue from injury.

Claims

1. A method of protecting a heart, liver or a portion of a liver contained within a host animal from injury resulting from controlled ischemia and reperfusion of the heart, liver or a portion of a liver, the method comprising administering to the host animal prior to the initial ischemic insult a mammalian High Mobility Group Box 1 (HMGB1) protein in an amount effective to protect the heart, liver or portion of a liver from injury.

2. The method of claim 1, wherein the HMGB1 protein comprises a polypeptide having the amino acid sequence of SEQ ID NO:

2.

3. The method of claim 1, wherein the HMGB1 protein consists of a polypeptide having the amino acid sequence of SEQ ID NO:

2.

4. The method of claim 1, wherein the HMGB1 protein is administered about one hour prior to the injury.

5. The method of claim 1, wherein the HMGB1 protein is administered about 45 minutes prior to the injury.

6. The method of claim 1, wherein the HMGB1 protein is administered about 30 minutes prior to the injury.

7. The method of claim 1, wherein the HMGB1 protein is administered about 15 minutes prior to the injury.

8. The method of claim 1, wherein the HMGB1 protein is administered about 10 minutes prior to the injury.

9. The method of claim 1, wherein the HMGB1 protein is administered about 5 minutes prior to the injury.

10. The method of claim 1, wherein the host is a human.

11. The method of claim 1, wherein the host is a non-human mammal.

12. The method of claim 1, wherein the HMGB1 protein is administered systemically to the host.

13. The method of claim 1, wherein the HMGB1 protein is administered by a route selected from the group consisting of intravenous, intramuscular, intraperitoneal, percutaneous, subcutaneous, topical, transmucosal, or oral.

14. The method of claim 1, wherein the HMGB1 protein is administered locally to the heart, liver or a portion of a liver.

15. The method of claim 1, wherein the HMGB1 protein is administered in a dosage of about 5 μ

g to about 35 mg.

16. The method of claim 15, wherein the HMGB1 protein is administered in a dosage of about 5 μ

g to about 20 μ

g.

17. The method of claim 15, wherein the HMGB1 protein is administered in a dosage of about 20 μ

g to about 1 mg.

18. The method of claim 15, wherein the HMGB1 protein is administered in a dosage of about 1 mg to about 10 mg.

19. The method of claim 15, wherein the HMGB1 protein is administered in a dosage of about 10 mg to about 35 mg.

20. The method of claim 1, wherein the injury resulting from controlled ischemia and reperfusion occurs during transplantation of the heart, liver or portion of a liver from a donor to a recipient, and wherein the HMGB1 protein is administered to the donor prior to the initial ischemic insult.

21. The method of claim 1, wherein the ischemia and reperfusion occur during a surgical procedure.

22. The method of claim 1, wherein the heart, liver or a portion of a liver is a heart.

23. The method of claim 1, wherein the heart, liver or a portion of a liver is a liver or a portion of a liver.

24. The method of claim 1, wherein the host animal is a donor of the heart, liver or portion of the liver.

25. The method of claim 24, wherein the donor is a cadaver donor.

26. The method of claim 24, wherein the donor is a human.

27. The method of claim 24, wherein the donor is a non-human mammal.

28. The method of claim 24, wherein the HMGB1 protein is administered systemically to the donor.

29. The method of claim 1, wherein the HMGB1 protein is administered locally to the heart, liver or portion of the liver.

30. The method of claim 24, wherein the HMGB1 protein is administered by a route selected from the group consisting of intravenous, intramuscular, intraperitoneal, percutaneous, subcutaneous, transmucosal, topical, or oral.