Use of a PPAR-δ agonist for reducing loss of muscle strength, muscle mass, or type I muscle fibers in an immobilized limb

Patent metadata

Field	Value
Publication number	US-10456406-B2
Application number	US-201815950949-A
Country	US
Kind code	B2
Filing date	Apr 11, 2018
Priority date	Sep 9, 2013
Publication date	Oct 29, 2019
Grant date	Oct 29, 2019

Abstract

The present invention provides methods for reducing loss of muscle strength, muscle mass, or Type I muscle fibers in an immobilized limb by administering (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.

First claim

We claim:

1. A method of treating muscle atrophy in a subject comprising administering to the subject in need thereof (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 (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:
increases muscle mass in the subject;
modulates muscle growth, enhances muscle formation, increases muscle strength, maintains muscle strength or reduces loss of muscle strength in the subject; or
reduces the rate of decrease in mitochondrial biogenesis in a muscle tissue; or
combination thereof.

3. A method of modulating muscle in a subject with muscle atrophy comprising administering to the subject in need thereof (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,
wherein the muscle modulation is selected from:
increasing muscle mass in the subject;
modulating muscle growth, enhancing muscle formation, increasing muscle strength, maintaining muscle strength or reducing loss of muscle strength in the subject; or
reducing the rate of decrease in mitochondrial biogenesis in a muscle tissue; or combination thereof.

4. The method of claim 1 , wherein (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,
reduces the rate of loss of Type I muscle fibers.

5. The method of claim 1 , wherein:
the treatment comprises activating PPARδ in skeletal muscle in the subject.

6. The method of claim 5 , wherein:
the muscle atrophy is skeletal muscle atrophy secondary to a chronic disease.

7. The method of claim 6 , wherein:
the chronic disease is a neurologic disease or drug-induced muscle disease.

8. The method of claim 6 , wherein:
the chronic disease is multiple sclerosis, amyotrophic lateral sclerosis, spinal muscular atrophy, critical illness neuropathy, cancer, congestive heart failure, chronic pulmonary disease, chronic renal failure, chronic liver disease, diabetes mellitus, Cushing syndrome, chronic infection, glucorticoid-induced myopathy, statin-induced myopathy, polymyositis or dermatomyositis.

9. The method of claim 1 , wherein:
the muscle atrophy is skeletal muscle atrophy secondary to a genetic disease that primarily affect skeletal muscle.

10. The method of claim 9 , wherein:
the genetic disease is muscular dystrophy or myotonic dystrophy.

11. The method of claim 1 , wherein:
(E)-[4-[3-(4-Fluorophenyl)-3-[4-[3-(morpholin-4-yl)propynyl]phenyl]allyloxy]-2-methyl-phenoxy]acedic acid, or a pharmaceutically acceptable salt thereof, is administered at a dose of 50-200 mg per day.

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

• A61K9/0053

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

• C07D295/096

  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

• A61K31/5375 Primary

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

• A61K31/192

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