Methods and compositions 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 for increasing red blood cell levels in a patient, the method comprising administering to a patient in need thereof a polypeptide selected from the group consisting of a BMP9 polypeptide comprising an amino acid sequence that is at least 90% identical to the sequence of SEQ ID NO: 3 and a BMP10 polypeptide comprising an amino acid sequence that is at least 90% identical to the sequence of SEQ ID NO: 6, wherein the polypeptide binds to ALK1 and increases red blood cell levels when administered to the patient.
2. The method of claim 1 , wherein the polypeptide is a BMP9 polypeptide that comprises an amino acid sequence that is at least 95% identical to the sequence of SEQ ID NO: 3.
3. The method of claim 2 , wherein the BMP9 polypeptide comprises an amino acid sequence that is at least 97% identical to the sequence of SEQ ID NO.: 3.
4. The method of claim 2 , wherein the BMP9 polypeptide comprises an amino acid sequence that is at least 98% identical to the sequence of SEQ ID NO: 3.
5. The method of claim 2 , wherein the BMP9 polypeptide comprises an amino acid sequence that is at least 99% identical to the sequence of SEQ ID NO.: 3.
6. The method of claim 1 , wherein the polypeptide is a BMP10 polypeptide that comprises an amino acid sequence that is at least 95% identical to the sequence of SEQ ID NO: 6.
7. The method of claim 6 , wherein the BMP10 polypeptide comprises an amino acid sequence that is at least 97% identical to the sequence of SEQ ID NO.: 6.
8. The method of claim 6 , wherein the BMP10 polypeptide comprises an amino acid sequence that is at least 98% identical to the sequence of SEQ ID NO: 6.
9. The method of claim 6 , wherein the BMP10 polypeptide comprises an amino acid sequence that is at least 99% identical to the sequence of SEQ ID NO.: 6.
10. The method of claim 1 , wherein the BMP9 polypeptide or BMP10 polypeptide is administered in a pharmaceutical preparation.
11. The method of claim 10 , wherein the pharmaceutical preparation comprises a prodomain polypeptide selected from the group consisting of a BMP9 prodomain polypeptide and a BMP10 prodomain polypeptide.
12. The method of claim 11 , wherein the prodomain polypeptide is a BMP9 prodomain polypeptide.
13. The method of claim 12 , 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.
14. The method of claim 12 , wherein the prodomain polypeptide comprises the amino acid sequence of amino acids 23-319 of SEQ ID NO.: 1.
15. The method of claim 12 , wherein the pharmaceutical preparation comprises a BMP9 polypeptide noncovalently associated with the BMP9 prodomain polypeptide.
16. The method of claim 12 , wherein the pharmaceutical preparation comprises a BMP10 polypeptide noncovalently associated with the BMP9 prodomain polypeptide.
17. The method of claim 11 , wherein the prodomain polypeptide is a BMP10 prodomain polypeptide.
18. The method of claim 17 , wherein the prodomain polypeptide comprises an amino acid sequence that is at least 80% identical to the sequence of amino acids 22-316 of SEQ ID NO.: 4.
19. The method of claim 17 , wherein the prodomain polypeptide comprises the amino acid sequence of amino acids 22-316 of SEQ ID NO.: 4.