Cardiac muscle function and manipulation

• US 7,964,555 B2
• Filed: 05/04/2006
• Issued: 06/21/2011
• Est. Priority Date: 12/21/1998
• Status: Expired due to Fees

• Current Assignee: Zensun (Shanghai) Science & Technology, Co., Ltd.
• Original Assignee: Zensun SCI & Tech Company Limited
• Inventors: Zhou, Mingdong
• Primary Examiner(s): AUDET, MAURY A
• Application Number:
  US11/429,203
• Publication Number:
  US 20060194734A1
• Time in Patent Office: 1,874 Days
• Field of Search: 514/12
• US Class Current: 514/1.1
• CPC Class Codes: A61K 38/1883 Neuregulins, e.g.. p185erbB2 ligands, glial growth factor, heregulin, ARIA, neu differentiation factor
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C12N 5/0657 Cardiomyocytes; Heart cells
• CPC Class Codes: G01N 2333/4756 Neuregulins, i.e. p185erbB2 ligands, glial growth factor, heregulin, ARIA, neu differentiation factor
• CPC Class Codes: G01N 2800/32 Cardiovascular disorders
• CPC Class Codes: G01N 2800/325 Heart failure or cardiac arrest, e.g. cardiomyopathy, congestive heart failure
• CPC Class Codes: G01N 33/6887 from muscle, cartilage or connective tissue
• CPC Class Codes: G01N 33/74 involving hormones or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors

Abstract

A method of causing cardiomyocyte growth and/or differentiation, the method comprising exposing a cardiomyocyte to neuregulin (NRG) thereby activating the MAP kinase pathway in the cardiomyocyte and causing growth and/or differentiation of the cardiomyocyte. Use of neuregulin, neuregulin polypeptide, neuregulin derivatives, or compounds which mimic the activities of neuregulins in the treatment or management of heart disease and heart failure in a mammal.

Claims

1. A method for providing a therapeutic treatment for heart failure in a mammal in need thereof, comprising administering an effective amount of polypeptide consisting of the amino acid sequence of SEQ ID NO:

2 to the mammal, wherein the heart failure is associated with cardiomyopathy, hypertension or myocarditis.

2. The method of claim 1, wherein the mammal is a human.

3. The method of claim 1, wherein the heart failure is characterized by disassociation of cardiac muscle cell-cell adhesion and/or the disarray of sarcomeric structures in the mammal.

4. The method of claim 1, wherein the polypeptide is administered with a pharmaceutically acceptable carrier, excipient or stabilizer.

5. The method of claim 1, further comprising administering an angiotensin-converting enzyme (ACE) inhibitor, or an agent for treating hypertension.

6. The method of claim 1, wherein the polypeptide is administered intravenously.

7. The method of claim 1, wherein the polypeptide is encoded by the nucleic acid sequence set forth in SEQ ID NO:

1.

8. The method of claim 1, wherein the polypeptide is administered by a gene therapy method.

9. The method of claim 1, wherein the polypeptide is administered by an adenovirus or adeno-associated virus.

10. The method of claim 1, wherein the polypeptide is administered in a sustained-release manner.

11. The method of claim 1, wherein administration of the polypeptide decreases DNA synthesis in cardiac muscle cells.

12. The method of claim 1, wherein the amount of polypeptide administered achieves a ligand concentration of at least 10⁻

8 M.

13. The method of claim 1, wherein the heart failure is associated with cardiomyopathy.

14. The method of claim 13, wherein the heart failure is associated with dilated cardiomyopathy or ischemic cardiomyopathy.

15. The method of claim 1, wherein the heart failure is associated with hypertension.

16. The method of claim 1, wherein the heart failure is associated with myocarditis.

17. The method of claim 16, wherein the heart failure is associated with viral myocarditis.

18. A method for providing a therapeutic treatment for heart failure in a mammal in need thereof, comprising administering an effective amount of polypeptide consisting of the amino acid sequence of SEQ ID NO:

2 to the mammal, wherein the heart failure is characterized by the heart not pumping blood at the rate needed for the requirements of metabolizing tissues.

19. The method of claim 18, wherein the mammal is a human.

20. The method of claim 18, wherein the heart failure is characterized by disassociation of cardiac muscle cell-cell adhesion and/or the disarray of sarcomeric structures in the mammal.

21. The method of claim 18, wherein the heart failure is caused by a drug treatment.

22. The method of claim 21, wherein the drug is fludrocortisone acetate or herceptin.

23. The method of claim 21, wherein the polypeptide is administered prior to, during or after said mammal is treated with said drug.

24. The method of claim 18, wherein the polypeptide is administered with a pharmaceutically acceptable carrier, excipient or stabilizer.

25. The method of claim 18, further comprising administering an angiotensin-converting enzyme (ACE) inhibitor or an agent for treating hypertension.

26. The method of claim 18, wherein the polypeptide is administered intravenously.

27. The method of claim 18, wherein the polypeptide is encoded by the nucleic acid sequence set forth in SEQ ID NO:

1.

28. The method of claim 18, wherein the polypeptide is administered by a gene therapy method.

29. The method of claim 18, wherein the polypeptide is administered by an adenovirus or adeno-associated virus.

30. The method of claim 18, wherein the polypeptide is administered in a sustained-release manner.

31. The method of claim 18, wherein the heart failure is associated with cardiomyopathy, hypertension or myocarditis.

32. The method of claim 18, wherein the heart failure is congestive heart failure.

33. The method of claim 18, wherein administration of the polypeptide decreases DNA synthesis in cardiac muscle cells.

34. The method of claim 18, wherein the amount of polypeptide administered achieves a ligand concentration of at least 10⁻

8 M.

35. A method for improving cardiac function in a mammal with heart failure, comprising administering an effective amount of polypeptide consisting of the amino acid sequence of SEQ ID NO:

2 to the mammal.

36. The method of claim 35, wherein the mammal is a human.

37. The method of claim 35, wherein the heart failure is characterized by disassociation of cardiac muscle cell-cell adhesion and/or the disarray of sarcomeric structures in the mammal.

38. The method of claim 35, wherein the heart failure is caused by a drug treatment.

39. The method of claim 38, wherein the drug is fludrocortisone acetate or herceptin.

40. The method of claim 38, wherein the polypeptide is administered prior to, during or after said mammal is treated with said drug.

41. The method of claim 35, wherein the polypeptide is administered with a pharmaceutically acceptable carrier, excipient or stabilizer.

42. The method of claim 35, further comprising administering an angiotensin-converting enzyme (ACE) inhibitor or an agent for treating hypertension.

43. The method of claim 35, wherein the polypeptide is administered intravenously.

44. The method of claim 35, wherein the polypeptide is encoded by the nucleic acid sequence set forth in SEQ ID NO:

1.

45. The method of claim 35, wherein the polypeptide is administered by a gene therapy method.

46. The method of claim 35, wherein the polypeptide is administered by an adenovirus or adeno-associated virus.

47. The method of claim 35, wherein the polypeptide is administered in a sustained-release manner.

48. The method of claim 35, wherein the heart failure is associated with cardiomyopathy, hypertension or myocarditis.

49. The method of claim 35, wherein the heart failure is congestive heart failure.

50. The method of claim 35, wherein administration of the polypeptide decreases DNA synthesis in cardiac muscle cells.

51. The method of claim 35, wherein the amount of polypeptide administered achieves a ligand concentration of at least 10⁻

8 M.