Methods for Treatment with Bucindolol Based on Genetic Targeting

Abstract

The present invention concerns the use of methods for evaluating bucindolol treatment for a patient, particularly one with heart failure. It concerns methods for determining whether to administer or prescribe bucindolol to a patient based on whether the patient is homozygous for the Arg 389 polymorphism in the β1-adrenergic receptor (AR).

1 .- 70 . (canceled) 
     
     
         71 . A method for measuring peak systolic force after treatment with isoproterenol comprising:
 a) administering isoproterenol to isolated right ventricular trabeculae from a failing human heart determined to be either homozygous Arg389 or carrier Gly389 in the β 1 -adrenergic receptor (AR) gene;   b) measuring peak systolic force.   
     
     
         72 . The method of  claim 71 , wherein isoproterenol is administered to isolated right ventricular trabeculae from at least one failing human heart determined to be homozygous Arg389 in the β 1 -AR gene. 
     
     
         73 . The method of  claim 71 , wherein isoproterenol is administered to isolated right ventricular trabeculae from at least one failing human heart determined to be homozygous carrier Gly389 in the β 1 -AR gene. 
     
     
         74 . The method of  claim 71 , wherein isoproterenol is administered to isolated right ventricular trabeculae from at least one failing human heart determined to be homozygous Arg389 in the β 1 -AR gene and at least one failing human heart determined to be homozygous carrier Gly389 in the β 1 -AR gene. 
     
     
         75 . The method of  claim 74 , wherein the measured levels of peak systolic force from failing human heart(s) determined to be homozygous Arg389 in the β 1 -AR gene are compared to the measured levels of peak systolic force from failing human heart(s) determined to be homozygous carrier Gly389 in the β 1 -AR gene. 
     
     
         76 . The method of  claim 71 , further comprising administering isoproterenol to isolated right ventricular trabeculae from at least one nonfailing human heart determined to be either homozygous Arg389 or Gly389 in the β 1 -adrenergic receptor (AR) gene and measuring peak systolic force. 
     
     
         77 . The method of  claim 76 , wherein isoproterenol is administered to isolated right ventricular trabeculae from at least one nonfailing human heart determined to be homozygous Arg389 in the β 1 -AR gene. 
     
     
         78 . The method of  claim 76 , wherein isoproterenol is administered to isolated right ventricular trabeculae from at least one nonfailing human heart determined to be homozygous carrier Gly389 in the β 1 -AR gene. 
     
     
         79 . The method of  claim 76 , wherein isoproterenol is administered to isolated right ventricular trabeculae from at least one nonfailing human heart determined to be homozygous Arg389 in the β 1 -AR gene and at least one nonfailing human heart determined to be homozygous carrier Gly389 in the β 1 -AR gene. 
     
     
         80 . The method of  claim 79 , wherein the measured levels of peak systolic force from nonfailing human heart(s) determined to be homozygous Arg389 in the β 1 -AR gene are compared to the measured levels of peak systolic force from nonfailing human heart(s) determined to be homozygous carrier Gly389 in the β 1 -AR gene. 
     
     
         81 . The method of  claim 71 , wherein isoproterenol is administered in different concentrations to multiple isolated right ventricular trabeculae. 
     
     
         82 . The method of  claim 71 , wherein the measured peak systolic force is between 0 and 20 mN/mm 2 . 
     
     
         83 . A method for measuring peak systolic force after treatment with isoproterenol comprising:
 a) administering isoproterenol to isolated right ventricular trabeculae from
 i) failing human hearts determined to be homozygous Arg389 in the β 1 -adrenergic receptor (AR) gene; 
 ii) failing human hearts determined to be carrier Gly389 in the β 1 -AR gene; 
 iii) nonfailing human hearts determined to be homozygous Arg389 in the β 1 -adrenergic receptor (AR) gene; and 
 ii) nonfailing human hearts determined to be carrier Gly389 in the β 1 -AR gene; 
   b) measuring peak systolic force in the isolated right ventricular trabeculae.   
     
     
         84 . The method of  claim 83 , wherein isoproterenol is administered in different concentrations to multiple isolated right ventricular trabeculae. 
     
     
         85 . The method of  claim 83 , wherein the measured peak systolic force is between 0 and 20 mN/mm 2 . 
     
     
         86 . A method comprising:
 a) administering different concentrations of isoproterenol to isolated right ventricular trabeculae from
 i) failing human hearts determined to be homozygous Arg389 in the β 1 -adrenergic receptor (AR) gene; 
 ii) failing human hearts determined to be carrier Gly389 in the β 1 -AR gene; 
 iii) nonfailing human hearts determined to be homozygous Arg389 in the β 1 -adrenergic receptor (AR) gene; and 
 ii) nonfailing human hearts determined to be carrier Gly389 in the β 1 -AR gene; 
   b) measuring peak systolic force in the isolated right ventricular trabeculae.   
     
     
         87 . The method of  claim 86 , wherein the measured peak systolic force is between 0 and 20 mN/mm 2 .