Alpha Connexin c-Terminal (ACT) peptides for use in transplant

Patent metadata

Field	Value
Publication number	US-9408381-B2
Application number	US-201514932630-A
Country	US
Kind code	B2
Filing date	Nov 4, 2015
Priority date	Dec 21, 2004
Publication date	Aug 9, 2016
Grant date	Aug 9, 2016

Abstract

The present disclosure provides compositions and methods for treating or preventing macular degeneration in a subject. The disclosure also provides compositions and methods for preserving organs and tissues for transplantation, and for preventing cellular injury in organs or in subjects.

First claim

What is claimed is:

1. A method of preserving an organ for organ transplantation comprising incubating the organ with a solution comprising an isolated polypeptide consisting of the carboxy terminal most 4 to 30 contiguous amino acids of an alpha connexin, or a conservative variant thereof.

2. The method of claim 1 , wherein the organ is selected from the group consisting of heart, kidneys, liver, lungs, pancreas, intestine, and thymus.

3. The method of claim 2 , wherein the organ is a kidney.

4. The method of claim 2 , wherein the organ is a heart.

5. The method of claim 1 , wherein the polypeptide inhibits cellular injury in the organ.

6. The method of claim 5 , wherein the polypeptide inhibits endothelial cellular injury.

7. The method of claim 5 , wherein the polypeptide inhibits epithelial cellular injury.

8. The method of claim 5 , wherein the cellular injury is caused by cold preservation induced damage.

9. The method of claim 5 , wherein the cellular injury is caused by hypoxia.

10. The method of claim 5 , wherein the cellular injury is ischemia reperfusion injury (IRI).

11. The method of claim 5 , wherein the cellular injury is ischemic reperfusion induced graft injury.

12. The method of claim 1 , wherein the polypeptide promotes cell-cell communication in the organ.

13. The method of claim 1 , wherein the polypeptide stabilizes gap junctions in cells of the organ.

14. The method of claim 1 , wherein the polypeptide stabilizes tight junctions in cells of the organ.

15. The method of claim 1 , wherein the polypeptide inhibits or mitigates hemichannel activity in cells of the organ.

16. The method of claim 1 , wherein the polypeptide inhibits apoptosis in cells of the organ.

17. The method of claim 1 , wherein the polypeptide inhibits mitochondrial oxidant production in cells of the organ.

18. The method of claim 1 , wherein the polypeptide promotes the integrity of endothelial cells of the organ.

19. The method of claim 1 , wherein the polypeptide promotes barrier function of endothelial cells of the organ.

20. The method of claim 1 , wherein the polypeptide inhibits pro-inflammatory cytokine release from cells in the organ.

21. The method of claim 20 , wherein the pro-inflammatory cytokine is IL-8.

22. The method of claim 1 , wherein the polypeptide comprises the amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, and SEQ ID NO: 5.

23. The method of claim 22 , wherein the polypeptide comprises the amino acid sequence of SEQ ID NO: 2.

24. The method of claim 1 , wherein the alpha connexin is connexin 37, connexin 40, connexin 43, or connexin 45.

25. The method of claim 1 , wherein the polypeptide is present in the solution at a concentration of about 10 to about 500 M.

26. The method of claim 1 , wherein the polypeptide is present in the solution at a concentration of about 100 pM.

Assignees

• Musc Found For Res Dev

Inventors

• Ghatnekar Gautam
• Gourdie Robert
• Jourdan Jane

Classifications

• A61K38/1709

  from mammals · CPC title

• C07K14/705

  Receptors; Cell surface antigens; Cell surface determinants {(tumour specific antigens C07K14/4748)} · CPC title

• A61K38/177

  Receptors; Cell surface antigens; Cell surface determinants · CPC title

• A01N1/122

  Preservation or perfusion media · CPC title

• A01N1/126 Primary

  Physiologically active agents, e.g. antioxidants or nutrients · CPC title