Methods of use of fibroblast growth factor, vascular endothelial growth factor and related proteins in the treatment of acute and chronic heart disease

• US 6,759,386 B2
• Filed: 04/06/2001
• Issued: 07/06/2004
• Est. Priority Date: 04/06/2000
• Status: Expired due to Fees

• Current Assignee: Wayne P. Franco
• Original Assignee: Wayne P. Franco
• Inventors: Franco, Wayne P.
• Primary Examiner(s): Kemmerer, Elizabeth
• Assistant Examiner(s): NICHOLS, CHRISTOPHER J
• Application Number:
  US09/828,330
• Publication Number:
  US 20020058612A1
• Time in Patent Office: 1,187 Days
• Field of Search: 514/2, 514/8, 514/169, 514/456, 514/12, 514/14, 424/84, 424/46, 424/434, 424/435, 424/489, 424/493, 530/300
• US Class Current: 514/8.1
• CPC Class Codes: A61K 38/1825 Fibroblast growth factor [FGF]
• CPC Class Codes: A61K 38/1866 Vascular endothelial growth factor [VEGF]
• CPC Class Codes: G01N 2800/32 Cardiovascular disorders
• CPC Class Codes: G01N 2800/324 Coronary artery diseases, e.g. angina pectoris, myocardial infarction
• CPC Class Codes: G01N 33/6893 related to diseases not provided for elsewhere

Abstract

Disclosed herein is a rational, multi-tier approach to the administration of growth factor proteins in the treatment of heart disease. Also disclosed is a method to evaluate the effectiveness of the administration of growth factor proteins comprising the clinical assay of CPK-MB levels in a patient undergoing treatment with growth factor proteins. In addition, there is disclosed a method for treatment of heart disease comprising administration of a therapeutically effective amount of a growth factor protein by oral inhalation therapy.

Claims

1. A method for the systematic, multi-tiered treatment of coronary artery disease by delivey of a formulation comprising one or more therapeutic growth factor proteins, the method comprising the steps of:

a.) selecting a patient displaying symptoms of acute coronary artery disease;

b.) administrating at least one dose of an effective amount of a first therapeutic growth factor protein formulation comprising a growth factor protein being selected from the group consisting of FGF-1, FGF-2, VEGF, and mixtures thereof by inhalation therapy;

c.) monitoring one or more clinical indicators of acute coronary artery disease;

d.) determining, based on monitoring the one or more clinical indicators of coronary artery disease, whether an additional dose of a therapeutic growth factor protein formulation is neceasary;

e.) depending on the results of the step d.), administering one or more additional doses of a second growth factor protein formulation comprising a growth factor protein being selected from the group consisting of FGF-1, FGF-2, VEGF, and mixtures thereof; and

f.) repeating steps c.) through e.) until there is a clinical indication of amelioration of the symptoms of acute coronary artery disease in the patient, or until there is a contraindication to continued treatment.

2. The method of claim 1, wherein the second growth factor protein is administered by a method of delivery more invasive than the method of delivery utilized for administration of the first growth factor protein formulation.

3. The method of claim 1, wherein the second growth factor protein is administered by the same method of delivery utilized foe administration of the previous dose.

4. The method claim 1, wherein the one or more clinical indicators of acute coronary artery disease are selected from the group consisting of levels of CPK-MB, electrocardiogram tracings, and chest pain.

5. The method of claim 1, wherein the symptoms of acute coronary artery disease are brought on by a condition selected from the group consisting of myocardial infarct, unstable angina, and acute anginal attack.

6. The method of claim 1, wherein the method of delivery of the second growth factor protein formulation is selected from the group consisting of oral inhalation, intravenous administration, intracoronary infusion, intrapericardial injection, myocardial introduction via catheter during cardiac catherization, and direct myocardial injection.

7. The method of claim 1, wherein the growth factor formulation administered in step e.) and subsequent steps is the same as the growth factor formulation administered initially.

8. The method of claim 1, wherein the growth factor formulation administered in step e.) and subsequent steps is different from the growth factor formulation administered initially.

9. The method of claim 1, wherein each of said first and second therapeutic growth factor protein formulations comprise FGF-1 and/or FGF-2.

10. The method of claim 1, wherein each of said first and second therapeutic growth factor protein formulations comprise VEGF.

11. The method of claim 1, wherein at least one of said first and second therapeutic growth factor protein formulations is a dry powder formulation.

12. The method of claim 1, wherein at least one of said first and second therapeutic growth factor protein formulations is a liquid aerosol formulation.

13. The method of claim 1, wherein the acute symptoms of heart disease are brought on by reperfusion injury.

14. The method of claim 13, wherein the reperfusion injury is induced by a procedure selected from the group consisting of thrombolytic therapy, bypass surgery and angioplasty.

15. A method for the systematic, multi-tiered treatment of chronic coronary artery disease by delivery of a formulation comprising one or more therapeutic growth factor proteins, the method comprising the steps of:

a.) selecting a patient displaying symptoms of chronic coronary artery disease;

b.) administering at least one dose of an effective amount of a first therapeutic growth factor protein formulation comprising a growth factor protein being selected from the group consisting of FGF-1, FGF-2, VEGF, and mixtures thereof, by inhalation therapy;

c.) monitoring one or more clinical indicators of chronic coronary artery disease;

d.) determining, based on monitoring the one or more clinical indicators of chronic coronary artery disease, whether an additional dose of a therapeutic growth factor protein formulation is necessary;

e.) depending on the results of step d.), administering one or more additional doses of a second growth factor protein formulation comprising a growth factor protein being selected from the group consisting of FGF-1, FGF-2, VEGF, and mixtures thereof; and

f.) repeating steps c.) through e.) until there is a clinical indication of amelioration of the symptoms of chronic artery disease in the patient, or until there is a contraindication to continued treatment.

16. The method of claim 15, wherein the amelioration of symptoms is achieved as a result of a clinically significant amount of angiogenesis.

17. The method of claim 15, wherein the second growth factor protein formulation is administered by the same method of delivery utilized for the administration of the previous dose.

18. The method of claim 15, wherein the second growth factor protein formulation is administered by a method of delivery more invasive than the method of delivery utilized for the administration of the first growth protein formulation.

19. The method of claim 15, wherein the one or more clinical indicators of chronic coronary artery disease are selected from the group consisting of frequency and intensity of anginal symptoms, myocardial perfusion, electrocardiogram tracings, scores on quantitative angina scales, and angiography.

20. The method of claim 15, wherein the method of delivery of the second growth factor protein formulation is selected from the group consisting of oral inhalation, intravenous administration, intracoronary infusion, intrapericardial injection, myocardial introduction via catheter during cardiac catherization, introduction during transmyocardial revascularization and direct myocardial injection.

21. The method of claim 15, wherein the growth factor formulation administered in step e.) and subsequent steps is the same as the growth factor formulation administered initially.

22. The method of claim 15, wherein the growth factor formulation administered in step e.) and subsequent steps is different from the growth factor formulation administered initially.

23. The method of claim 15, wherein each of said first and second therapeutic growth factor protein formulations comprise FGF-1 and/or FGF-2.

24. The method of claim 15, wherein each of said first and second therapeutic growth factor protein formulations comprise VEGF.