COMPOSITIONS, KITS, AND METHODS TO INDUCE ACQUIRED CYTORESISTANCE USING STRESS PROTEIN INDUCERS

• US 20170112869A1
• Filed: 01/06/2017
• Published: 04/27/2017
• Est. Priority Date: 09/29/2014
• Status: Active Grant

• Current Assignee: Fred Hutchinson Cancer Center
• Original Assignee: Fred Hutchinson Cancer Research Center (Fred Hutchinson Cancer Research Center|Argus Genetics|Mars)
• Inventors: Zager, Richard A., Johnson, Ali CM
• Granted Patent: US 9,844,563 B2
• Time in Patent Office: Days
• CPC Class Codes: A01N 1/0226 Physiologically active agents, i.e. substances affecting physiological processes of cells and tissue to be preserved, e.g. anti-oxidants or nutrients
• CPC Class Codes: A61K 31/194 having two or more carboxyl groups, e.g. succinic, maleic or phthalic acid
• CPC Class Codes: A61K 31/555 containing heavy metals, e.g. hemin, hematin, melarsoprol
• CPC Class Codes: A61K 31/714 Cobalamins, e.g. cyanocobalamin, i.e. vitamin B12
• CPC Class Codes: A61K 33/26 Iron; Compounds thereof
• CPC Class Codes: A61K 38/42 Haemoglobins; Myoglobins
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 11/00 Drugs for disorders of the respiratory system
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: A61P 37/06 Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07H 23/00 Compounds containing boron, silicon, or a metal, e.g. chelates, vitamin B12 esters with inorganic acids C07H11/00; metal salts, see parent compounds

Abstract

The present disclosure provides compositions, kits, and methods to protect organs by inducing acquired cytoresistance without causing injury to the organ. The compositions, kits, and methods utilize heme proteins, iron and/or vitamin B12 and, optionally, agents that impact heme protein metabolism.

Claims

1. A method of protecting an organ from injury based on a scheduled insult comprising administering to the organ a therapeutically effective amount of a composition comprising vitamin B12, iron, or a combination thereof, before the scheduled insult to the organ occurs, wherein the administering protects the organ from the injury without causing injury to the organ.

2. A method of claim 1, wherein the composition comprises vitamin B12.

3. A method of claim 1, wherein the composition comprises iron.

4. A method of claim 1, wherein the composition comprises the combination of iron and vitamin B12.

5. A method of claim 1, wherein the scheduled insult is surgery, chemotherapy, or radiocontrast toxicity.

6. A method of claim 1, wherein the organ is a heart, kidney, liver, or lung.

7. A method of claim 2, wherein the composition further comprises a heme protein degradation inhibitor.

8. A method of claim 7, wherein the heme protein degradation inhibitor is a nitrited heme protein degradation inhibitor.

9. A method of claim 2, further comprising administering to the organ a second composition comprising a heme protein degradation inhibitor.

10. A method of claim 7, wherein the heme protein degradation inhibitor is a heme oxygenase inhibitor.

11. A method of claim 10, wherein the heme oxygenase inhibitor is a protoporphyrin, hemin, or hematin.

12. A method of claim 10, wherein the heme oxygenase inhibitor is a metal protoporphyrin.

13. A method of claim 12, wherein the metal protoporphyrin is Sn-protoporphyrin.

14. A method of up-regulating expression of protective stress proteins in an organ before a scheduled insult comprising administering to the organ a therapeutically effective amount of a composition comprising a heme protein, vitamin B12, iron, or a combination thereof, wherein the administering up-regulates expression of protective stress proteins in the organ without causing injury to the organ and protects the organ from injury based on the scheduled insult.

15. A method of claim 14, wherein the composition comprises vitamin B12.

16. A method of claim 14, wherein the composition comprises iron.

17. A method of claim 14, wherein the composition comprises the combination of the vitamin B12 and the iron.

18. A method of claim 14, wherein the administration occurs at least 8 hours before the scheduled insult.

19. A method of claim 14, wherein the scheduled insult is surgery, chemotherapy, or radiocontrast toxicity.

20. A method of claim 14, wherein the organ is a heart, kidney, liver, or lung.

21. A method of claim 14, wherein the protective stress proteins are selected from heme oxygenase, haptoglobin, hemopexin, hepcidin, alpha-1 antitrypsin, interleukin-10, heat-shock proteins, neutrophil gelatinase-associated lipocalin, or HMG CoA reductase.

22. A method of claim 14, wherein the composition further comprises a heme protein degradation inhibitor.

23. A method of claim 22, wherein the heme protein degradation inhibitor is a nitrited heme protein degradation inhibitor.

24. A method of claim 14, further comprising administering to the organ a second composition comprising a heme protein degradation inhibitor.

25. A method of claim 22, wherein the heme protein degradation inhibitor is a heme oxygenase inhibitor.

26. A method of claim 25, wherein the heme oxygenase inhibitor is a protoporphyrin, hemin, or hematin.

27. A method of claim 25, wherein the heme oxygenase inhibitor is a metal protoporphyrin.

28. A method of claim 27, wherein the metal protoporphyrin is Sn-protoporphyrin.