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

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.

1 - 36 . (canceled)  
     
     
         37 . A method for the systemic, multi-tiered treatment of acute or 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) administering at least one dose of an effective amount of a first therapeutic growth factor protein formulation comprising: 
 1. a growth factor protein selected from the group consisting of FGF-1 and FGF-2, and mixtures thereof; and  
 2. a growth factor protein selected from the group consisting of VEGF, VEGF-A, VEGF-B, VEGF-165, and PIGF, and mixtures thereof;  
   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 indicators;    e) determining, based on monitoring the effectiveness of stem cell treatment by echo-cardiogram and/or other clinical indicators, whether an additional dose of stem cells is indicated or whether an additional dose of growth factor protein is indicated;    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    if indicated, repeating steps b) through e) until there is a clinical indication of amelioration of the symptoms of acute or chronic heart disease in the patient, or until there is contraindication to continued treatment.    
     
     
         38 . The method of  claim 37 , wherein said at least one dose of an effective amount of a first therapeutic growth factor protein formulation is administered via intracoronary infusion.  
     
     
         39 . The method of  claim 37 , wherein said at least one dose of an effective amount of a first therapeutic growth factor protein formulation is administered via direct myocardial injection.  
     
     
         40 . The method of  claim 37 , wherein said at least one dose of an effective amount of a first therapeutic growth factor protein formulation is administered via intracoronary infusion during bypass surgery or angioplasty.  
     
     
         41 . The method of  claim 37 , wherein said at least one dose of an effective amount of a first therapeutic growth factor protein formulation is administered via direct myocardial injection during bypass surgery or angioplasty.  
     
     
         42 . The method of  claim 37 , wherein said at least one dose of an effective amount of a first therapeutic growth factor protein formulation is administered via intravenous injection.  
     
     
         43 . The method of  claim 37 , wherein said at least one dose of an effective amount of a first therapeutic growth factor protein formulation is administered via intrapericardial injection.  
     
     
         44 . The method of  claim 37 , wherein said at least one dose of an effective amount of a first therapeutic growth factor protein formulation is administered via endomyocardial injection during heart catheterization.  
     
     
         45 . The method of  claim 37 , wherein the symptoms of acute 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.  
     
     
         46 . The method of  claim 45 , wherein the reperfusion injury is induced by a procedure selected from the group consisting of thrombolytic therapy, bypass surgery and angioplasty.  
     
     
         47 . The method of  claim 37  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.  
     
     
         48 . The method of  claim 37  wherein the second growth factor is administered by the same method of delivery utilized for administration of the previous dose.  
     
     
         49 . The method of  claim 37  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.  
     
     
         50 . The method of  claim 37. , wherein the growth factor formulation administered in step e) and subsequent steps is the same as the growth factor formulation administered initially.  
     
     
         51 . The method of  claim 37 , wherein the growth factor formulation administered in step e) and subsequent steps is different from the growth factor formulation administered initially.  
     
     
         52 . The method of  claim 37  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.  
     
     
         53 . The method of  claim 37  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.  
     
     
         54 . The method of  claim 37  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.  
     
     
         55 . The method of  claim 37 , wherein the stem cells have been isolated from the patient.  
     
     
         56 . The method of  claim 37 , wherein the stem cells have been isolated from an HLA-matched individual.  
     
     
         57 . The method of  claim 37 , wherein the stem cells are peripheral blood stem cells.  
     
     
         58 . The method of  claim 37 , wherein the stem cells are bone marrow stem cells.  
     
     
         59 . The method of  claim 37  wherein the stem cells are purified by fluorescence-activated cell sorting.  
     
     
         60 . The method of  claim 37  wherein the stem cells are purified by density gradient centrifugation.  
     
     
         61 . The method of  claim 37  wherein step e) further includes monitoring the effectiveness of administration of adult stem cells by stress echo-cardiogram.