METHODS OF MODULATING APOPTOSIS BY ADMINISTRATION OF RELAXIN AGONISTS OR ANTAGONISTS

• US 20110059108A1
• Filed: 11/12/2010
• Published: 03/10/2011
• Est. Priority Date: 10/04/2000
• Status: Active Grant

• Current Assignee: Korea Medicine Research Institute
• Original Assignee: Korea Medicine Research Institute
• Inventors: Samuel, Chrishan S., Amento, Edward P.
• Granted Patent: US 8,119,136 B2
• Time in Patent Office: Days
• US Class Current: 424/158.1
• 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 increasing apoptosis in a population of cells expressing a human relaxin receptor, comprising:

administering to the population cells of an effective amount of an antagonist of rexlain for a period of time sufficient to increase apoptosis in the cell population expressing the relaxin receptor, as compared to the level of apoptosis in the cell population not contacted with the antagonist,

wherein said antagonist of relaxin is a relaxin receptor binding agent, a relaxin analog, or a double relaxin receptor.

2. The method of claim 1, wherein the relaxin antagonist inhibits binding of relaxin to relaxin receptor.

3. The method of claim 1, wherein the relaxin antagonist reduces relaxin-associated tissue remodeling.

4. The method of claim 1, wherein the cell population is from heart, brain, liver, kidney, spleen, thymus, skin, female reproductive tract tissue or male reproductive tract tissue.

5. The method of claim 4, wherein the male reproductive tract tissue is prostate, epididymis, seminal vesicles or testes.

6. The method of claim 5, wherein the tissue is prostatic tissue.

7. The method of claim 4, wherein the male reproductive tract tissue is mature.

8. The method of claim 4, wherein the tissues of the female reproductive tract are the uterus, cervix, the interpubic ligament, and connective tissues within the pelvic girdle.

9. The method of claim 1, wherein the cell population comprises fibroblasts, osteoblasts, monocytes, epithelial cells or endothelial cells.

10. 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.

11. The method of claim 10, wherein the administering is by delayed release delivery.

12. The method of claim 10, wherein the subcutaneous delivery is by infusion or injection.

13. The method of claim 10, wherein the administering is by intrapulmonary, subcutaneous or transdermal delivery.

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

15. The method of claim 1, wherein the vector is an expression vector, and whereby the relaxin antagonist is expressed in the cell population.

16. The method of claim 1, wherein increased apoptosis reduces unwanted cell accumulation.

17. The method of claim 16, wherein the unwanted cells accumulation is hyperplasia, hypertrophy, cancer or neoplasia.