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

• US 7,091,179 B2
• Filed: 12/09/2003
• Issued: 08/15/2006
• 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:
  US10/731,197
• Publication Number:
  US 20040167070A1
• Time in Patent Office: 980 Days
• Field of Search: 424/9.1, 514/2, 514/8, 514/12, 514/14, 530/300, 530/324, 530/399
• 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 monitoring the clinical effectiveness of the administration of a formulation comprising one or more therapeutic growth factor proteins in the treatment of coronary artery disease, the method comprising the steps of:

a. selecting a patient displaying symptoms of 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 selected from the group consisting of FGF-1, FGF-2, VEGF-B, and mixtures thereof by inhalation therapy;

c. obtaining a sample of a biological fluid from the patient displaying symptoms of coronary artery disease;

d. performing an assay of the biological fluid to determine an amount of CPK-MB present in the fluid;

e. determining, based on monitoring the amount of CPK-MB present in the fluid, whether an additional dose of a therapeutic growth factor protein formulation is necessary;

f. depending on the results of the step e), 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-B, and mixtures thereof; and

g. repeating steps c) through f) until the assayed levels of CPK-MB in the biological fluid indicates the clinical effectiveness of the administration of the pharmaceutical formulation and amelioration of the symptoms of coronary artery disease in the patient, or until there is a contraindication to continued treatment.

2. The method of claim 1 wherein the growth factor protein formulation is a dry powder formulation.

3. The method of claim 1 wherein the growth factor protein formulation is a liquid aerosol formulation.

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

5. The method of claim 4, wherein the reperfusion injury is induced by a procedure selected from the group consisting of thrombolytic therapy, bypass surgery and angioplasty.

6. A method for monitoring the clinical effectiveness of the administration of a potentially therapeutic pharmaceutical formulation selected from the group consisting of FGF-1, FGF-2, VEGF-B, and mixtures thereof, in the treatment of chronic coronary artery disease, 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 selected from the group consisting of FGF-1, FGF-2, VEGF-B, 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 the step e), 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-B, and mixtures thereof; and

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

7. The method of claim 6 wherein the growth factor protein formulation is a dry powder formulation.

8. The method of claim 6 wherein the growth factor protein formulation is a liquid aerosol formulation.