Methods for increasing vascularization
View Patent ↗Disclosed are methods of increasing vascularization in a tissue by administering a neublastin polypeptide to a mammal exhibiting impaired or inadequate blood flow in the tissue. The methods can be used to in the treatment or prevention of a disorder characterized by impaired or inadequate blood flow or to increase vascularization in an organ that has been transplanted into a subject.
1. A method of treating a skin lesion in skin tissue having impaired or inadequate blood flow, the method comprising
administering to a human in need of such treatment a therapeutically effective amount of a polypeptide that comprises an amino acid sequence that is at least 80% identical to amino acids 15-113 of SEQ ID NO:1, wherein the polypeptide, when dimerized, binds to a complex containing GFRalpha3 and RET.
2. The method of claim 1 , wherein the skin lesion is associated with a diabetic ulcer.
3. The method of claim 2 , wherein the diabetic ulcer is a diabetic foot ulcer.
4. The method of claim 1 , further comprising administering to the human one or more of an antithrombotic agent, a factor other than neublastin that increases vascularization, a cholesterol-lowering agent, a beta blocker, an anti-hypertensive agent, or an immunosuppressive agent.
5. The method of claim 1 , further comprising determining whether increased vascularization has occurred subsequent to administration of the polypeptide.
6. The method of claim 1 , wherein the polypeptide is administered to the human via systemic administration.
7. The method of claim 1 , wherein the polypeptide is administered to the human via subcutaneous administration.
8. The method of claim 1 , wherein the polypeptide is administered to the human via local administration.
9. The method of claim 1 , wherein the amino acid sequence is at least 90% identical to amino acids 15-113 of SEQ ID NO:1.
10. The method of claim 1 , wherein the amino acid sequence is at least 95% identical to amino acids 15-113 of SEQ ID NO:1.
11. The method of claim 1 , wherein the amino acid sequence is at least 98% identical to amino acids 15-113 of SEQ ID NO:1.
12. The method of claim 1 , wherein the polypeptide comprises amino acids 15-113 of SEQ ID NO:1, amino acids 15-113 of SEQ ID NO:2, amino acids 15-113 of SEQ ID NO:3, amino acids 15-113 of SEQ ID NO:4, amino acids 15-113 of SEQ ID NO:5, amino acids 15-113 of SEQ ID NO:8, or amino acids 15-113 of SEQ ID NO:9.
13. The method of claim 1 , wherein the polypeptide comprises the amino acid sequence of SEQ ID NO:1, the amino acid sequence of SEQ ID NO:2, the amino acid sequence of SEQ ID NO:3, the amino acid sequence of SEQ ID NO:4, the amino acid sequence of SEQ ID NO:5, the amino acid sequence of SEQ ID NO:8, or the amino acid sequence of SEQ ID NO:9.
14. The method of claim 1 , wherein the polypeptide comprises amino acids 10-113 of SEQ ID NO:1.
15. The method of claim 1 , wherein the human has not been diagnosed with a neurological disorder.
16. The method of claim 1 , wherein the human has not been diagnosed with an ocular disorder.
17. The method of claim 2 , wherein the amino acid sequence is at least 90% identical to amino acids 15-113 of SEQ ID NO:1.
18. The method of claim 2 , wherein the amino acid sequence is at least 95% identical to amino acids 15-113 of SEQ ID NO:1.
19. The method of claim 2 , wherein the amino acid sequence is at least 98% identical to amino acids 15-113 of SEQ ID NO:1.
20. The method of claim 2 , wherein the polypeptide comprises amino acids 15-113 of SEQ ID NO:1, amino acids 15-113 of SEQ ID NO:2, amino acids 15-113 of SEQ ID NO:3, amino acids 15-113 of SEQ ID NO:4, amino acids 15-113 of SEQ ID NO:5, amino acids 15-113 of SEQ ID NO:8, or amino acids 15-113 of SEQ ID NO:9.
21. The method of claim 2 , wherein the polypeptide comprises the amino acid sequence of SEQ ID NO:1, the amino acid sequence of SEQ ID NO:2, the amino acid sequence of SEQ ID NO:3, the amino acid sequence of SEQ ID NO:4, the amino acid sequence of SEQ ID NO:5, the amino acid sequence of SEQ ID NO:8, or the amino acid sequence of SEQ ID NO:9.
22. The method of claim 2 , wherein the polypeptide comprises amino acids 10-113 of SEQ ID NO:1.
23. The method of claim 3 , wherein the amino acid sequence is at least 90% identical to amino acids 15-113 of SEQ ID NO:1.
24. The method of claim 3 , wherein the amino acid sequence is at least 95% identical to amino acids 15-113 of SEQ ID NO:1.
25. The method of claim 3 , wherein the amino acid sequence is at least 98% identical to amino acids 15-113 of SEQ ID NO:1.
26. The method of claim 3 , wherein the polypeptide comprises amino acids 15-113 of SEQ ID NO:1, amino acids 15-113 of SEQ ID NO:2, amino acids 15-113 of SEQ ID NO:3, amino acids 15-113 of SEQ ID NO:4, amino acids 15-113 of SEQ ID NO:5, amino acids 15-113 of SEQ ID NO:8, or amino acids 15-113 of SEQ ID NO:9.
27. The method of claim 3 , wherein the polypeptide comprises the amino acid sequence of SEQ ID NO:1, the amino acid sequence of SEQ ID NO:2, the amino acid sequence of SEQ ID NO:3, the amino acid sequence of SEQ ID NO:4, the amino acid sequence of SEQ ID NO:5, the amino acid sequence of SEQ ID NO:8, or the amino acid sequence of SEQ ID NO:9.
28. The method of claim 3 , wherein the polypeptide comprises amino acids 10-113 of SEQ ID NO:1.
29. The method of claim 1 , wherein the polypeptide consists of amino acids 10-113 of SEQ ID NO:1.
30. The method of claim 2 , wherein the polypeptide consists of amino acids 10-113 of SEQ ID NO:1.
31. The method of claim 3 , wherein the polypeptide consists of amino acids 10-113 of SEQ ID NO:1.