Methods for treating ulcers in a hemoglobinopathy anemia with a soluble actRIIB polypeptide
The present disclosure provides compositions and methods for treating or preventing ulcers in subjects having low red blood cell levels and/or hemoglobin levels (e.g, anemia). In some embodiments, the compositions of the disclosure may be used to treat or prevent ulcers associated with anemia.
1. A method for treating a cutaneous ulcer in a subject that has a hemoglobinopathy anemia, comprising administering to the subject an ActRIIB polypeptide; wherein the polypeptide comprises an amino acid sequence that is at least 85% identical to the sequence of amino acids 29-109 of SEQ ID NO: 1.
2. The method of claim 1 , wherein the polypeptide comprises 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.
3. The method of claim 1 , wherein the polypeptide is a fusion protein further comprising an immunoglobulin Fc domain.
4. The method of claim 3 , wherein the fusion protein further comprises a linker domain positioned between the polypeptide and the immunoglobulin Fc domain.
5. The method of claim 1 , wherein the polypeptide comprises one or more amino acid modifications selected from: a glycosylated amino acid, a PEGylated amino acid, a farnesylated amino acid, an acetylated amino acid, a biotinylated amino acid, and an amino acid conjugated to a lipid moiety.
6. The method of claim 1 , wherein the polypeptide comprises an amino acid sequence that is 95% identical to amino acids 29-109 of SEQ ID NO: 1, and wherein the polypeptide comprises an acidic amino acid at the position corresponding to position 79 of SEQ ID NO: 1.
7. The method of claim 1 , wherein the polypeptide comprises amino acids 29-109 of SEQ ID NO: 1, but wherein the polypeptide comprises an acidic amino acid at the position corresponding to position 79 of SEQ ID NO: 1.
8. The method of claim 1 , wherein the polypeptide comprises an amino acid sequence that is at least 85% identical to the sequence of amino acids 25-131 of SEQ ID NO: 1, and wherein the polypeptide comprises an acidic amino acid at the position corresponding to position 79 of SEQ ID NO: 1.
9. The method of claim 1 , wherein the polypeptide comprises an amino acid sequence that is at least 90% identical to the sequence of amino acids 25-131 of SEQ ID NO: 1, and wherein the polypeptide comprises an acidic amino acid at the position corresponding to position 79 of SEQ ID NO: 1.
10. 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 25-131 of SEQ ID NO: 1, and wherein the polypeptide comprises an acidic amino acid at the position corresponding to position 79 of SEQ ID NO: 1.
11. The method of claim 1 , wherein the polypeptide comprises amino acids 25-131 of SEQ ID NO: 1, but wherein the polypeptide comprises an acidic amino acid at the position corresponding to position 79 of SEQ ID NO: 1.
12. The method of claim 1 , wherein the polypeptide comprises an amino acid sequence that is at least 85% identical to SEQ ID NO: 44, and wherein the polypeptide comprises an acidic amino acid at the position corresponding to position 79 of SEQ ID NO: 1.
13. The method of claim 1 , wherein the polypeptide comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 44, and wherein the polypeptide comprises an acidic amino acid at the position corresponding to position 79 of SEQ ID NO: 1.
14. The method of claim 1 , wherein the polypeptide comprises an amino acid sequence that is at least 95% identical to SEQ ID NO: 44, and wherein the polypeptide comprises an acidic amino acid at the position corresponding to position 79 of SEQ ID NO: 1.
15. The method of claim 1 , wherein the polypeptide comprises the amino acid sequence of SEQ ID NO: 44, but wherein the polypeptide comprises an acidic amino acid at the position corresponding to position 79 of SEQ ID NO: 1.
16. The method of claim 1 , wherein the polypeptide inhibits signaling by GDF8 in a cell-based assay.
17. The method of claim 1 , wherein the polypeptide inhibits signaling by GDF11 in a cell-based assay.
18. The method of claim 1 , wherein the amino acid at the position corresponding to position 79 of SEQ ID NO: 1 is an aspartic acid.
19. The method of claim 1 , wherein the amino acid at the position corresponding to position 79 of SEQ ID NO: 1 is a glutamic acid.
20. The method of claim 1 , wherein the polypeptide binds GDF8.
21. The method of claim 1 , wherein the polypeptide binds GDF11.