Methods and compositions using GDF15 polypeptides for increasing red blood cells
In certain aspects, the present invention provides compositions and methods for increasing red blood cell and/or hemoglobin levels in vertebrates, including rodents and primates, and particularly in humans.
1. A method of treating anemia associated with acute blood loss in a human patient, the method comprising administering to a patient in need thereof an effective amount of a GDF15 polypeptide and an erythropoietin receptor activator, wherein the GDF15 polypeptide comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 8; and wherein the GDF15 polypeptide is capable of binding to ALK5.
2. The method of claim 1 , wherein the GDF15 polypeptide comprises an amino acid sequence that is encoded by a nucleic acid that hybridizes to the a nucleic acid that is complementary to the sequence of nucleotides 589-924 of SEQ ID NO: 13.
3. The method of claim 1 , wherein the GDF15 polypeptide is administered in a pharmaceutical preparation.
4. The method of claim 3 , wherein the pharmaceutical preparation comprises a GDF15 prodomain polypeptide.
5. The method of claim 4 , wherein the GDF15 prodomain polypeptide comprises an amino acid sequence that is at least 90% identical to the sequence of amino acids 30-196 of SEQ ID NO: 1.
6. The method of claim 4 or 5 , wherein the pharmaceutical preparation comprises a GDF15 polypeptide noncovalently associated with the GDF15 prodomain polypeptide.