Neuregulin based methods and compositions for treating cardiovascular disease
View Patent ↗The present invention relates to compositions and methods for preventing, treating or delaying various cardiovascular diseases or disorders in mammals, particularly in humans. More particularly, the present invention provides for compositions and methods for preventing, treating or delaying various cardiovascular diseases or disorders using, inter alia, a neuregulin protein, or a functional fragment thereof, or a nucleic acid encoding a neuregulin protein, or a functional fragment thereof, or an agent that enhances production and/or function of said neuregulin.
1. A method for treating myocardial infarction or heart failure caused by myocardial infarction in a mammal, comprising administering to a mammal in need thereof a neuregulin 1 protein in an amount from about 10 U/kg to about 400 U/kg of body weight of the mammal once a day.
2. The method of claim 1 , wherein the neuregulin 1 protein carries out its anti-myocardial infarction activity via binding with ErbB2-ErbB4 receptors.
3. The method of claim 1 , wherein the neuregulin 1 protein is neuregulin α2 or neuregulin β2.
4. The method of claim 1 , wherein the neuregulin 1 protein comprises the amino acid sequence of SEQ ID NO:4.
5. The method of claim 1 , wherein the neuregulin 1 protein antagonizes the increase of left ventricular end-diastolic (LVEDD) and end-systolic diameters (LVESD) associated with the myocardial infarction.
6. The method of claim 1 , wherein the neuregulin 1 protein antagonizes the decrease of left ventricular EF associated with the myocardial infarction.
7. The method of claim 1 , wherein the mammal is a human.
8. The method of claim 1 , wherein the myocardial infarction has a clinical feature selected from the group consisting of left ventricular dilation, reduced systolic function and increased filling pressure.
9. The method of claim 1 , wherein the neuregulin 1 protein is administered with a pharmaceutically acceptable carrier or excipient.
10. The method of claim 1 , further comprising administering a prophylactic or therapeutic agent for myocardial infarction.
11. The method of claim 10 , wherein the neuregulin 1 protein is administered prior to, concurrently with, or subsequent to the administration of the prophylactic or therapeutic agent.
12. The method of claim 10 , wherein the prophylactic or therapeutic agent is selected from the group consisting of an angiotensin I-converting enzyme inhibitor (ACEI), a calcium antagonist, a β-receptor antagonist, aspirin, atropine, nitroglycerin, scopolamine and a thrombolytic agent.
13. The method of claim 12 , wherein the ACEI is selected from the group consisting of Captopril, Rampril, Lisinopril, Zofenopril and Trandolapril.
14. The method of claim 12 , wherein the calcium antagonist is diltiazem.
15. The method of claim 12 , wherein the β-receptor antagonist is selected from the group consisting of propranolol, metoprolol, atenolol and timolol.
16. The method of claim 12 , wherein the thrombolytic agent is selected from the group consisting of streptokinase, t-PA and anistreplase.
17. The method of claim 1 , wherein the neuregulin 1 protein is administered in vivo.
18. The method of claim 1 , wherein the neuregulin 1 protein is administered for about 21 days or less than 21 days.
19. The method of claim 1 , wherein the neuregulin 1 protein is administered for a period of between 3 days and 21 days.
20. The method of claim 3 , wherein the neuregulin 1 protein is neuregulin α2.
21. The method of claim 3 , wherein the neuregulin 1 protein is neuregulin β2.
22. The method of claim 8 , wherein the myocardial infarction has the clinical feature of left ventricular dilation.
23. The method of claim 8 , wherein the myocardial infarction has the clinical feature of reduced systolic function.
24. The method of claim 8 , wherein the myocardial infarction has the clinical feature of increased filling pressure.
25. The method of claim 11 , wherein the neuregulin 1 protein is administered prior to the administration of the prophylactic or therapeutic agent.
26. The method of claim 11 , wherein the neuregulin 1 protein is administered concurrently with the administration of the prophylactic or therapeutic agent.
27. The method of claim 11 , wherein the neuregulin 1 protein is administered subsequent to the administration of the prophylactic or therapeutic agent.
28. The method of claim 12 , wherein the prophylactic or therapeutic agent is an angiotensin I-converting enzyme inhibitor (ACEI).
29. The method of claim 12 , wherein the prophylactic or therapeutic agent is a calcium antagonist.
30. The method of claim 12 , wherein the prophylactic or therapeutic agent is a β-receptor antagonist.
31. The method of claim 12 , wherein the prophylactic or therapeutic agent is aspirin.
32. The method of claim 12 , wherein the prophylactic or therapeutic agent is atropine.
33. The method of claim 12 , wherein the prophylactic or therapeutic agent is nitroglycerin.
34. The method of claim 12 , wherein the prophylactic or therapeutic agent is scopolamine.
35. The method of claim 12 , wherein the prophylactic or therapeutic agent is a thrombolytic agent.
36. The method of claim 13 , wherein the ACEI is Captopril.
37. The method of claim 13 , wherein the ACEI is Rampril.
38. The method of claim 13 , wherein the ACEI is Lisinopril.
39. The method of claim 13 , wherein the ACEI is Zofenopril.
40. The method of claim 13 , wherein the ACEI is Trandolapril.
41. The method of claim 15 , wherein the β-receptor antagonist is propranolol.
42. The method of claim 15 , wherein the β-receptor antagonist is metoprolol.
43. The method of claim 15 , wherein the β-receptor antagonist is atenolol.
44. The method of claim 15 , wherein the β-receptor antagonist is timolol.
45. The method of claim 16 , wherein the thrombolytic agent is streptokinase.
46. The method of claim 16 , wherein the thrombolytic agent is t-PA.
47. The method of claim 16 , wherein the thrombolytic agent is anistreplase.
48. The method of claim 18 , wherein the neuregulin 1 protein is administered for about 21 days.
49. The method of claim 18 , wherein the neuregulin 1 protein is administered for less than 21 days.