TREATMENT OF CONGESTIVE HEART FAILURE AND OTHER CARDIAC DYSFUNCTION USING A GDF15 MODULATOR
The invention provides methods and compositions of treating a subject having a cardiac-related disorder such as congestive or chronic heart failure (CHF), cardiac hypertrophy, cardiac hypotrophy, and other cardiac myopathies/dystrophies. The methods comprise administering an effective amount of a composition that modulates, for example, reduces or inhibits, GDF 15 activity in the subject.
1 . A method of increasing cardiac function in a subject in need thereof, the method comprising administering an effective amount of a composition comprising a GDF15 modulator thereby to increase cardiac function in said subject.
2 . The method of claim 1 , wherein the subject has elevated GDF15 activity in a body fluid.
3 . A method of treating a subject having a cardiac disorder or dysfunction, the method comprising administering an effective amount of a composition comprising a GDF15 modulator thereby to ameliorate a symptom of the cardiac disorder or dysfunction.
4 . The method of claim 3 , wherein the subject has elevated GDF15 activity in a body fluid.
5 . A method of reducing or reversing cardiac hypotrophy in a subject exhibiting one or more symptoms of congestive heart failure, the method comprising administering an effective amount of a composition comprising a GDF15 modulator, wherein the composition ameliorates at least one symptom of cardiac hypotrophy in the subject.
6 . The method of claim 5 , wherein the subject has elevated GDF15 activity in a body fluid.
7 . A method of treating or preventing congestive heart failure (CHF) in a subject in need thereof, the method comprising administering an effective amount of a composition that reduces or inhibits a GDF15 activity in the subject, thereby to treat or prevent CHF in the subject.
8 . The method of claim 7 , wherein the subject has elevated GDF15 activity in a body fluid.
9 . A method of reducing cardiac hypotrophy in a subject exhibiting one or more characteristics of congestive heart failure, the method comprising administering an effective amount of a composition that modulates the activity of GDF15, thereby to reduce cardiac hypotrophy in the subject.
10 . The method of claim 9 , wherein the subject has elevated GDF15 activity in a body fluid.
11 . The method of any one of claims 1 - 10 , wherein the subject exhibits a peak VO 2 of less than less than 14 mL/kg/min.
12 . The method of any one of claims 1 - 11 , wherein the subject exhibits an LVEF of less than 40%.
13 . The method of any one of claims 1 - 12 , wherein the subject exhibits BNP levels in excess of 100 pg/ml.
14 . The method of any one of claims 1 - 13 , wherein the subject exhibits serum cardiac troponin I (cTnI) levels in excess of 1.5 ng/mL.
15 . The method of any one of claims 1 - 14 , wherein the subject has been diagnosed as having congestive heart failure.
16 . The method of any one of claims 1 - 15 , wherein the GDF15 modulator reduces or inhibits GDF15 activity in the subject.
17 . The method of claim 16 , wherein the GDF15 modulator binds GDF15.
18 . The method of claim 17 , wherein the GDF15 inhibitor is an anti-GDF15 antibody.
19 . The method of claim 18 , wherein the antibody is humanized or human.
20 . The method of any one of claims 1 - 19 , wherein the subject exhibits above normal levels of a marker selected from the group consisting of cardiac troponin I, cardiac troponin T, brain natriuretic protein (BNP), N-terminal peptides derived from BNP (NT-proBNP), and cardiac fatty acid binding protein (cFABP).
21 . The method of any one of claim 2 , 4 , 6 , 8 , or 10 , wherein the body fluid is plasma or serum.