METHODS OF MODULATING APOPTOSIS BY ADMINISTRATION OF RELAXIN AGONISTS OR ANTAGONISTS

• US 20120238499A1
• Filed: 02/17/2012
• Published: 09/20/2012
• Est. Priority Date: 10/04/2000
• Status: Active Grant

• Current Assignee: Korea Medicine Research Institute
• Original Assignee: Korea Medicine Research Institute
• Inventors: Amento, Edward P., Samuel, Chrishan S.
• Granted Patent: US 9,534,034 B2
• Time in Patent Office: Days
• US Class Current: 514/12.7
• CPC Class Codes: A01K 2227/105 Murine
• CPC Class Codes: A01K 67/0276 Knock-out vertebrates
• CPC Class Codes: A61K 38/22 Hormones derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin A61K38/33, e.g. corticotropin A61K38/35
• CPC Class Codes: A61K 38/2221 Relaxins
• CPC Class Codes: A61P 1/00 Drugs for disorders of the alimentary tract or the digestive system
• 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 13/08 of the prostate
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/00 Drugs for disorders of the endocrine system
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C07K 14/64 Relaxins

Abstract

The present invention relates to the discovery that relaxin is associated with the development or maturation of body tissues. Knockouts of the gene encoding relaxin result in various abnormalities in the development of various tissues. The present invention provides methods of modulating apoptosis by administering a relaxin agonist or antagonist to a subject.

Claims

1. A method of modulating apoptosis, comprising:

administering to a subject in need thereof an effective amount of a relaxin agonist for a period of time sufficient to decrease apoptosis in cells expressing a relaxin receptor.

2. The method of claim 1, wherein the cells are from the liver, kidney, spleen, thymus, brain, heart, intestine, skin, lung, the male reproductive tract, or the female reproductive tract.

3. The method of claim 2, wherein the male reproductive tract tissue is prostate, epididymis, seminal vesicles or testes.

4. The method of claim 2, wherein the female reproductive tract tissue is uterus, cervix, the interpubic ligament, or connective tissues within the pelvic girdle.

13. The method of claim 1, wherein the subject has a relaxin-deficient condition.

14. The method of claim 13, wherein the relaxin-deficient condition is immature tissue, or low sperm count.

15. The method of claim 14, wherein the immature tissue is immature male reproductive tract tissue.

16. The method of claim 15, wherein the immature male reproductive tract tissue is underdeveloped testes.

18. The method of claim 1, wherein the relaxin agonist is relaxin, a relaxin analog, a small molecule relaxin effector, or a relaxin nucleic acid.

19. The method of claim 18, wherein the relaxin is vertebrate relaxin or human relaxin.

21. The method of claim 1, wherein the administering is by infusion, injection, oral delivery, nasal delivery, intrapulmonary delivery, rectal delivery, transdermal delivery, interstitial delivery or subcutaneous delivery.

22. The method of claim 21, wherein the administering is by delayed release delivery.

25. The method of claim 1, wherein the administering comprises delivery of a vector encoding the relaxin agonist.

26. The method of claim 1, wherein the vector is an expression vector, and whereby the relaxin agonist is expressed in the cells.

28. The method of claim 1, wherein the subject is a post-pubescent subject or a pre-pubescent subject.

5. (canceled)

6. A method for stimulating maturation, development or differentiation of an immature tissue, comprising administering to a subject in need thereof an effective amount of a relaxin agonist for a time period sufficient to stimulate tissue maturation.

8. The method of claim 6, wherein the tissue is male reproductive tract tissue.

9. The method of claim 8, wherein the tissue is prostatic tissue, epididymal tissue, seminiferous tissue, testicular tissue or sperm.

11. The method of claim 9, wherein the maturation is an increase in cell number in an under-developed testes.

12. The method of claim 9, wherein the number of viable sperm cells increases.

7. (canceled)

10. (canceled)

17. (canceled)

20. (canceled)

23-24. -24. (canceled)

27. (canceled)

29-52. -52. (canceled)