Methods for increasing red blood cell levels comprising administering BMP9
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 for increasing red blood cell levels or treating anemia in a patient, the method comprising administering to a patient in need thereof a BMP9polypeptide comprising an amino acid sequence that is at least 80% identical to the sequence of SEQ ID NO: 3, wherein the BMP9 polypeptide binds to ALK1 and increases red blood cell levels when administered to the patient.
2. The method of claim 1 , wherein the BMP9 polypeptide comprises an amino acid sequence that is at least 85% identical to the sequence of SEQ ID NO: 3.
3. A method for increasing red blood cell levels or treating anemia in a patient, the method comprising administering to a patient in need thereof a BMP9 polypeptide comprising an amino acid sequence that is at least 80% identical to the sequence of SEQ ID NO: 3, wherein the BMP9 polypeptide binds to ALK1 and increases red blood cell levels when administered to the patient, wherein the BMP9polypeptide comprises an amino acid sequence that is identical to the sequence of SEQ ID NO: 3.
4. The method of claim 1 , wherein the BMP9 polypeptide is administered in a pharmaceutical preparation.
5. The method of claim 4 , wherein the pharmaceutical preparation comprises a BMP9 prodomain polypeptide.
6. The method of claim 5 , wherein the prodomain polypeptide comprises an amino acid sequence that is at least 80% identical to the sequence of amino acids 23-319 of SEQ ID NO: 1.
7. The method of claim 5 , wherein the prodomain polypeptide comprises the amino acid sequence of amino acids 23-319 of SEQ ID NO: 1.
8. The method of claim 5 , wherein the pharmaceutical preparation comprises a BMP9 polypeptide noncovalently associated with the BMP9 prodomain polypeptide.
9. The method of claim 1 , wherein the patient has anemia associated with chronic kidney disease.
10. The method of claim 1 , wherein the patient has anemia associated with a chemotherapy treatment.
11. The method of claim 10 , wherein the chemotherapy treatment is a taxane.
12. The method of claim 1 , wherein the patient has anemia as a consequence of blood loss.
13. The method of claim 1 , wherein the BMP9 polypeptide comprises an amino acid sequence that is at least 90% identical to the sequence of SEQ ID NO: 3.
14. The method of claim 1 , wherein the BMP9 polypeptide comprises an amino acid sequence that is at least 95% identical to the sequence of SEQ ID NO: 3.
15. The method of claim 1 , wherein the BMP9 polypeptide stimulates SMAD 1/5/8 signaling.
16. The method of claim 1 , wherein the method is for increasing red blood cell levels in a patient in need thereof.
17. The method of claim 1 , wherein the method is for treating anemia in a patient in need thereof.