Inhibiting activity of senescent cells using a glucocorticoid

Patent metadata

Field	Value
Publication number	US-9884065-B2
Application number	US-201615077630-A
Country	US
Kind code	B2
Filing date	Mar 22, 2016
Priority date	Dec 13, 2011
Publication date	Feb 6, 2018
Grant date	Feb 6, 2018

Abstract

Methods are provided herein for enhancing the effectiveness of medical therapies by administering agents that suppress a biological damage response that is inducible by the medical therapy administered to a subject. In certain embodiments, a method is provided for administering an anti-senescent cell agent that suppresses a biological response comprising cellular senescence that is induced by the medical therapy.

First claim

We claim the following:

1. A method of inhibiting activity of a senescent cell in a cell population, wherein the senescent cell is characterized as expressing senescence-associated beta-galactosidase, the method comprising:
suppressing expression of senescence-associated secretory phenotype (SASP) by the senescent cell by applying to the cell population an amount of a glucocorticoid that is effective in causing expression of the SASP by the senescent cell to be suppressed; and
confirming that the amount of the glucocorticoid is effective by measuring expression of SASP by the cell population.

2. The method of claim 1 , wherein the amount of the glucocorticoid causes expression of IL-6 by the senescent cell to be suppressed.

3. The method of claim 1 , wherein the amount of the glucocorticoid causes expression of IL-6, IL-8, GM-CSF and MCP-2 by the senescent cell to be suppressed.

4. The method of claim 1 , wherein the amount of the glucocorticoid causes suppression of VEGF by the senescent cell to be suppressed.

5. The method of claim 1 , wherein the fraction of cells expressing senescence-associated beta-galactosidase is not altered in the cell population by the glucocorticoid.

6. The method of claim 1 , wherein the glucocorticoid is corticosterone.

7. The method of claim 1 , wherein the glucocorticoid is cortisol.

8. The method of claim 1 , wherein the senescent cell is contacted with the glucocorticoid in vitro.

9. The method of claim 1 , wherein the amount of the glucocorticoid reduces the likelihood of side effects mediated by the senescent cell following senescence inducing radiotherapy or chemotherapy.

10. The method of claim 9 , wherein the senescent cell is contacted with the glucocorticoid at least two days prior to administration of the radiotherapy or the chemotherapy.

11. The method of claim 1 , wherein the amount of the glucocorticoid improves the effectiveness of chemotherapy.

12. The method of claim 11 , wherein the amount of the glucocorticoid reduces the number of metastases of a primary tumor.

13. A method of reducing the likelihood of side effects of radiotherapy or chemotherapy in a subject that has cancer, comprising:
removing or reducing activity of senescent cells in the subject prior to administration of the radiotherapy or the chemotherapy by administering to the subject an effective amount of a glucocorticoid; and
confirming that as a consequence of administering the glucocorticoid, the activity of the senescent cells has been reduced by determining expression of senescence-associated secretory phenotype (SASP) by the senescent cells.

14. The method of claim 13 , wherein the subject is administered corticosterone or cortisol.

15. The method of claim 13 , wherein the removing or reducing activity of the senescent cells causes reduction in the number of metastases of the cancer in the subject.

Assignees

• Buck Inst Res Aging

Inventors

• Campisi Judith
• Laberge Remi Martin
• Rodier Francis
• Demaria Marco

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A01K2217/052

  inducing gain of function · CPC title

• A61K38/28

  Insulins · CPC title

• A61K31/573 Primary

  substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone · CPC title

• A61P31/12

  Antivirals · CPC title