Use of a PPAR-delta agonist for treating muscle atrophy

Patent metadata

Field	Value
Publication number	US-9487493-B2
Application number	US-201414478594-A
Country	US
Kind code	B2
Filing date	Sep 5, 2014
Priority date	Sep 9, 2013
Publication date	Nov 8, 2016
Grant date	Nov 8, 2016

Abstract

The present invention provides methods for treating muscle atrophy by administering a PPARδ agonist.

First claim

We claim:

1. A method for reducing disuse-associated muscle atrophy in a subject in need thereof comprising administering to the subject an effective amount of a PPARδ agonist, wherein the PPARδ agonist is (E)-[4-[3-(4-Fluorophenyl)-3-[4-[3-(morpholin-4-yl)propynyl]phenyl]allyloxy]-2-methyl-phenoxy]acetic acid or a pharmaceutically acceptable salt thereof.

2. The method of claim 1 , wherein the disuse-associated muscle atrophy is caused by limb immobilization in the subject.

3. The method of claim 1 , wherein the disuse-associated muscle atrophy is caused by use of a mechanical ventilator by the subject.

4. The method of claim 1 , wherein reducing disuse-associated muscle atrophy comprises reducing the rate of loss of muscle strength in a muscle tissue of the subject relative to a control, wherein the rate of loss of muscle strength comprises a comparison of one or more measurements of muscle strength in the subject to a baseline measurement of muscle strength in the same subject prior to a period of disuse, wherein muscle strength is measured by a muscle strength test.

5. The method of claim 4 , wherein reducing the rate of loss of muscle strength in the subject comprises a return to the subject's baseline measurement of muscle strength faster than the control following a period of disuse.

6. The method of claim 4 , wherein reducing the rate of loss of muscle strength in the subject comprises a return to the subject's baseline measurement of muscle strength following a period of disuse in less than 90% of the time to return to baseline for a control.

7. The method of claim 4 , wherein the loss of muscle strength in the subject is less than the loss of muscle strength relative to the control during a period of disuse.

8. The method of claim 4 , wherein the loss of muscle strength in the subject comprises less than a 10% loss of muscle strength relative to the subject's baseline measurement of muscle strength prior to a period of disuse.

9. The method of claim 1 , wherein reducing disuse-associated muscle atrophy comprises reducing the rate of loss of muscle mass in a muscle tissue of the subject relative to a control, wherein the rate of loss of muscle mass comprises a comparison of one or more measurements of muscle volume in the subject to a baseline measurement of muscle volume in the same subject, wherein muscle volume is measured by the cross-section area of a muscle.

10. The method of claim 9 , wherein reducing the rate of loss of muscle mass in the subject comprises a return to the subject's baseline measurement of muscle mass faster than the control.

11. The method of claim 9 , wherein reducing the rate of loss of muscle mass in the subject comprises a return to the subject's baseline measurement of muscle mass following a period of disuse in less than 90% of the time to return to baseline for a control.

12. The method of claim 9 , wherein the loss of muscle mass in the subject is less than the loss of muscle mass relative to the control.

13. The method of claim 9 , wherein the loss of muscle mass in the subject comprises less than a 10% loss of muscle mass relative to the subject's baseline measurement of muscle mass prior to a period of disuse.

14. The method of claim 1 , wherein reducing disuse-associated muscle atrophy comprises reducing the rate of loss of Type I muscle fibers in a muscle tissue of the subject relative to a control, wherein the rate of loss of Type I muscle fibers comprises a comparison of one or more measurements of Type I muscle fibers in the subject to a baseline measurement of Type I muscle fibers in the same subject.

15. The method of claim 1 , wherein reducing disuse-associated muscle atrophy comprises reducing the rate of decrease in mitochondrial biogenesis in a muscle tissue of the subject relative to a control, wherein the rate of decrease in mitochondrial biogenesis comprises a comparison of one or more measurements of mitochondrial biogenesis in the subject to a baseline measurement of mitochondrial biogenesis in the same subject.

16. The method of claim 1 , wherein the PPARδ agonist is administered to the subject in need thereof before, during, or after a period of disuse, or any combination thereof.

17. The method of claim 1 , wherein the effective amount of the PPARδ agonist is from 0.1 mg/day to 500 mg/day.

18. A method of reducing the period to weaning from a mechanical ventilator comprising administering to a subject a PPARδ agonist compound in an effective amount, wherein the PPARδ agonist compound is (E)-[4-[3-(4-Fluorophenyl)-3-[4-[3-(morpholin-4-yl)propynyl]phenyl]allyloxy]-2-methyl-phenoxy]acetic acid or a pharmaceutically acceptable salt thereof.

19. The method of claim 18 , wherein the subject is suffering from acute respiratory distress syndrome (ARDS).

20. The method of claim 18 , wherein the period to weaning from a mechanical ventilator is reduced by at least 24 hours.

Assignees

• Vtv Therapeutics Llc

Inventors

• Valcarce Lopez Maria Carmen
• Ohlstein Eliot

Classifications

• A61P21/00

  Drugs for disorders of the muscular or neuromuscular system · CPC title

• A61K31/5375 Primary

  1,4-Oxazines, e.g. morpholine · CPC title

• C07D295/096 Primary

  with the ring nitrogen atoms and the oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings · CPC title

• A61K9/0053

  Mouth and digestive tract, i.e. intraoral and peroral administration · CPC title

• A61K31/192

  having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid  {(cannabinoids A61K31/658)} · CPC title