Growth differentiation factor (gdf) for treatment of diastolic heart failure

Abstract

The methods and uses described herein relate to the treatment of age-related conditions, e.g. by administering an agent that inhibits the interaction of GDF11 and follistatin. In some embodiments, the agent can bind to an epitope of GDF11 as described herein.

What is claimed herein: 
     
         1 . A method of treating an age-related condition, the method comprising administering to a subject a follistatin-GDF11 inhibitor. 
     
     
         2 . The method of  claim 1 , wherein the age-related condition is selected from the group consisting of:
 a cardiovascular condition; aging of the heart; aging of skeletal muscle; aging of the brain; a metabolic disorder; and obesity.   
     
     
         3 . The method of  claim 1 , wherein the subject has or has been diagnosed with a condition selected from the group consisting of:
 diastolic heart failure; cardiac hypertrophy; age-related cardiac hypertrophy;   hypertension; valvular disease; aortic stenosis; genetic hypertrophic cardiomyopathy; or   stiffness of the heart due to aging.   
     
     
         4 . The method of  claim 1 , wherein the level of GDF11 polypeptide in the subject is increased. 
     
     
         5 . The method of  claim 4 , wherein in the level of GDF11 polypeptide is the level of free GDF11. 
     
     
         6 . The method of  claim 4 , wherein the level of GDF11 polypeptide is the level of GDF11 in the circulation of the subject. 
     
     
         7 . The method of  claim 4 , wherein the level of GDF11 polypeptide is the level of GDF11 in the cardiac tissue of the subject. 
     
     
         8 . The method of  claim 1 , wherein the follistatin-GDF11 inhibitor comprises an inhibitory nucleic acid; an antibody reagent; an antibody; or a small molecule. 
     
     
         9 . The method of  claim 1 , wherein the follistatin-GDF11 inhibitor comprises an antibody reagent that binds specifically to an epitope comprised by SEQ ID NO: 15 or SEQ ID NO: 16. 
     
     
         10 . The method of  claim 9 , wherein the antibody reagent is selected from the group consisting of:
 a humanized antibody reagent; a monoclonal antibody; and a humanized monoclonal antibody.   
     
     
         11 . The method of  claim 1 , wherein the composition is administered via a route selected from the group consisting of:
 intravenously; subcutaneously; intra-arterial; and intra-coronary arterial.   
     
     
         12 . The method of  claim 1 , wherein the level of GDF11 is increased by at least 100%. 
     
     
         13 . The method of  claim 1 , wherein the level of GDF11 is increased to at least 75% of a healthy reference level. 
     
     
         14 . A pharmaceutical composition comprising an isolated follistatin-GDF11 inhibitor and a pharmaceutically acceptable carrier.