Methods for treating refractory anemia with ringed sideroblasts
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 treating refractory anemia with ringed sideroblasts in a patient in need thereof, the method comprising administering to the patient an effective amount of a polypeptide comprising an amino acid sequence that is at least 90% identical to the sequence of amino acids 29-109 of SEQ ID NO: 1, wherein the polypeptide comprises an acidic amino acid at the position corresponding to position 79 of SEQ ID NO: 1, and wherein the polypeptide binds to GDF11 and/or myostatin.
2. The method of claim 1 , wherein the polypeptide comprises an amino acid sequence that is at least 95% identical to the sequence of amino acids 29-109 of SEQ ID NO: 1.
3. The method of claim 1 , wherein the acidic amino acid is glutamic acid.
4. The method of claim 1 , wherein the acidic amino acid is aspartic acid.
5. The method of claim 1 , wherein the polypeptide comprises one or more modified amino acid residues selected from: a glycosylated amino acid, a PEGylated amino acid, a farnesylated amino acid, an acetylated amino acid, a biotinylated amino acid, an amino acid conjugated to a lipid moiety, and an amino acid conjugated to an organic derivatizing agent.
6. The method of claim 1 , wherein the polypeptide binds to GDF11.
7. The method of claim 1 , wherein the polypeptide binds to myostatin.
8. The method of claim 1 , wherein the polypeptide binds to myostatin and GDF11.
9. The method of claim 1 , wherein the polypeptide inhibits signaling by GDF11 and myostatin in a cell-based assay.
10. The method of claim 1 , wherein the polypeptide inhibits signaling by GDF11 in a cell-based assay.
11. The method of claim 1 , wherein the polypeptide inhibits signaling by myostatin in a cell-based assay.
12. The method of claim 1 , wherein the polypeptide further comprises a constant region of an immunoglobulin.
13. The method of claim 12 , wherein the constant region is derived from an IgG heavy chain.
14. The method of claim 13 , wherein the constant region of an immunoglobulin is an Fc domain.
15. The method of claim 14 , wherein the polypeptide forms a homodimer.
16. The method of claim 1 , wherein the polypeptide comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 7.
17. The method of claim 1 , wherein the polypeptide comprises an amino acid sequence that is at least 95% identical to SEQ ID NO: 7.
18. The method of claim 1 , wherein the polypeptide comprises an amino acid sequence that is at least 99% identical to SEQ ID NO: 7.
19. The method of claim 1 , wherein the polypeptide comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 28.
20. The method of claim 1 , wherein the polypeptide comprises an amino acid sequence that is at least 95% identical to SEQ ID NO: 28.
21. The method of claim 1 , wherein the polypeptide comprises an amino acid sequence that is at least 99% identical to SEQ ID NO: 28.
22. The method of claim 1 , wherein the polypeptide comprises the amino acid sequence of SEQ ID NO: 7.
23. The method of claim 1 , wherein the polypeptide comprises the amino acid sequence of SEQ ID NO: 28.
24. The method of claim 23 , wherein the refractory anemia is associated with a myelodysplastic syndrome.
25. The method of claim 1 , wherein the refractory anemia is associated with a myelodysplastic syndrome.