Combination growth factor therapy and cell therapy for treatment of acute and chronic heart disease

• US 7,166,280 B2
• Filed: 11/18/2004
• Issued: 01/23/2007
• 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): Romeo; David S
• Assistant Examiner(s): Gamett; Daniel C
• Application Number:
  US10/991,592
• Publication Number:
  US 20050214260A1
• Time in Patent Office: 796 Days
• Field of Search: None
• US Class Current: 424/93.7
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 35/28 Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
• CPC Class Codes: A61K 38/1825 Fibroblast growth factor [FGF]
• CPC Class Codes: A61K 38/1866 Vascular endothelial growth factor [VEGF]
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• 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 2800/325 Heart failure or cardiac arrest, e.g. cardiomyopathy, congestive heart failure
• CPC Class Codes: G01N 33/6893 related to diseases not provided for elsewhere

Abstract

Acute and chronic heart disease is treated using a rational, multi-tier approach. A patient is pretreated with growth factor proteins or gene therapy, followed by the administration of adult stem cells. The progress of treatment is continuously monitored by echo-cardiogram with growth factor treatment and/or stem cell administration adjusted according to the results of the echo-cardiogram or clinical status of the patient. Heart disease is also treated by a method that comprises administration of a therapeutically effective amount of a growth factor protein by oral inhalation therapy.

Claims

1. A method for the systemic, multi-tiered treatment of acute and chronic cardiomyopathy by delivering a formulation comprising one or more therapeutic growth factor proteins together with adult stem cells, the method comprising the steps of:

a) selecting a patient displaying symptoms of acute or chronic cardiomyopathy;

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, VEGFA, VEGF165, and mixtures thereof by inhalation therapy;

c) following administration of at least one dose of an effective amount of a first therapeutic growth factor protein formulation, administrating at least one dose of an effective amount of adult stem cells;

d) monitoring the effectiveness of administration of adult stem cells by echo-cardiogram and/or other clinical indictors;

e) determining, based on monitoring the effectiveness of stem cell treatment by echo-cardiogram, whether an additional dose of stem cells is necessary or whether an additional dose of growth factor protein is indicted;

f) depending on the results of the step e), administering a second dose of an effective amount of adult stem cells and or growth factor proteins; and

g) if indicated, repeating steps b) through e) until there is a clinical indication of amelioration of amelioration of the symptoms of acute or chronic heart disease in the patient, or until there is 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 formulation.

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

4. The method of claim 1 wherein the method of delivery of the second growth factor formulation is selected from the group consisting of oral inhalation, intravenous injection, intracoronary infusion, intrapericardial, direct myocardial injection, and endomyocardial injection during heart catheterization.

5. 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.

6. 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.

7. The method of claim 1, wherein each of said first and second growth factor formulations comprises FGF-1 and/or FGF-2.

8. The method of claim 1, wherein each of said first and second growth factor formulations comprises VEGF and/or VEGFA and/or VEGF165.

9. The method of claim 1 wherein the second dose of adult stem cells is administered by a method of delivery more invasive than the method of delivery utilized for administration of the first dose of adult stem cells.

10. The method of claim 1 wherein the second dose of adult stem cells is administered by the same method of delivery utilized for administration of the first dose of adult stem cells.

11. The method of claim 1 wherein the method of delivery of the second dose of adult stem cells is selected from the group consisting of intravenous administration, intracoronary administration, endomyocardial administration, epimyocardial administration intramyocardial administration, or by intraventricular administration.

12. The method of claim 1, wherein each of said first and second growth factor formulations is a dry powder formulation.

13. The method of claim 1, wherein each of said first and second growth factor formulations is a liquid aerosol formulation.

14. The method of claim 1, wherein the stem cells have been isolated from the patient.

15. The method of claim 1, wherein the stem cells have been isolated from an HLA-matched individual.

16. The method of claim 1, wherein the stem cells are peripheral blood stem cells.

17. The method of claim 1, wherein the stem cells are bone marrow stem cells.

18. The method of claim 1 wherein the stem cells are purified by fluorescence-activated cell sorting.

19. The method of claim 1 wherein the stem cells are purified by density gradient centrifugation.

20. The method of claim 1 wherein step e) further includes monitoring the effectiveness of administration of adult stem cells by stress echo-cardiogram.

21. The method of claim 1 wherein the method is further used to help alleviate reperfusion injury before, during, and/or after thrombolytic therapy.