Methods for suppressing cancer-related cachexia

Patent metadata

Field	Value
Publication number	US-11219607-B2
Application number	US-201414547771-A
Country	US
Kind code	B2
Filing date	Nov 19, 2014
Priority date	Nov 20, 2013
Publication date	Jan 11, 2022
Grant date	Jan 11, 2022

Abstract

Methods of suppressing cachexia in a mammal with cancer comprising administering HDAC inhibitors are provided. Aspects include methods of administering an HDAC class 1 and 2b inhibitor in an amount effective to substantially maintain the mammal's weight compared to a mammal that does receive the HDAC class 1 and 2b inhibitor.

First claim

What is claimed is:

1. A method of restoring skeletal muscle weight in a mammal having cancer and loss of skeletal muscle weight associated with cancer-induced cachexia, comprising administering a composition comprising AR-42 to said mammal wherein the skeletal muscle weight is substantially restored compared to a mammal that does not receive AR-42.

2. The method of claim 1 , wherein the cancer is selected from the group consisting of pancreatic, colon, head, neck, gastric, lung, and esophageal.

3. The method of claim 1 , wherein the mammal is a human.

4. The method of claim 1 , wherein AR-42 is administered in an amount of about 1 mg/kg to about 100 mg/kg of the mammal.

5. The method of claim 4 , wherein AR-42 is administered at least once a day.

6. The method of claim 5 , wherein AR-42 is administered twice a day in an amount of about 50 mg/kg of the mammal.

7. The method of claim 1 , wherein levels of IL-6 are reduced by about 56% compared to a mammal that does not receive AR-42.

8. The method of claim 1 , wherein levels of LIF are reduced by about 88% compared to a mammal that does not receive AR-42.

9. The method of claim 1 , wherein expression of Atrogin-1 mRNA is restored to basal levels compared to a mammal that does not receive AR-42.

10. The method of claim 1 , wherein expression of MuRF1 mRNA is restored to basal levels compared to a mammal that does not receive AR-42.

11. The method of claim 1 , wherein expression of IL-6Rα mRNA is restored to basal levels compared to a mammal that does not receive AR-42.

12. The method of claim 1 , wherein a cachexia-induced loss of adipose tissue is substantially restored compared to a mammal that does not receive AR-42.

13. The method of claim 1 , wherein at least about 90% of said mammal's skeletal muscle weight is maintained over a period of time of at least fifteen days compared to a mammal that does not receive AR-42.

14. The method of claim 1 , wherein the cancer is lung cancer.

15. The method of claim 1 , wherein the cancer is prostate cancer.

Assignees

• Ohio State Innovation Foundation

Inventors

• Chen Ching-Shih
• Bekaii-Saab Tanios
• Guttridge Denis
• Marcucci Guido
• Kulp Samuel
• Tseng Yu-Chou

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61K31/166 Primary

  having the carbon of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol · CPC title

• A61P7/00

  Drugs for disorders of the blood or the extracellular fluid · CPC title

• A61K31/16 Primary

  Amides, e.g. hydroxamic acids · CPC title

• A61K31/167

  having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol · CPC title