Use of a ppar-delta agonist for reducing loss of muscle strength, muscle mass, or type I muscle fibers in an immobilized limb
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.
1. A method of treatment comprising administering to a human subject (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 human subject has an immobilized limb, and
wherein the amount of (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 administered is sufficient to reduce the rate of loss of muscle strength in the muscle tissue of the immobilized limb of the subject relative to a control,
wherein muscle strength is measured by a muscle strength test.
2. The method of claim 1 , wherein the rate of loss of muscle strength comprises a comparison of muscle strength in the subject's immobilized limb to a baseline measurement of muscle strength in the same limb prior to a period of immobilization.
3. The method of claim 1 , 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 immobilization.
4. The method of claim 1 , 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.
5. The method of claim 1 , wherein the loss of muscle strength in the subject's immobilized limb is less than the loss of muscle strength relative to the control during a period of immobilization.
6. 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 is administered orally.
7. A method of treatment comprising administering to a human subject (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 human subject has an immobilized limb, and
wherein the amount of (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 administered is sufficient to reduce the rate of loss of muscle mass in the muscle tissue of the immobilized limb 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.
8. The method of claim 7 , wherein reducing the rate of loss of muscle mass in the subject's immobilized limb comprises a return to the subject's baseline measurement of muscle mass faster than the control.
9. The method of claim 7 , wherein reducing the rate of loss of muscle mass in the subject's immobilized limb comprises a return to the subject's baseline measurement of muscle mass following a period of limb immobilization in less than 90% of the time to return to baseline for a control.
10. The method of claim 7 , wherein the loss of muscle mass in the subject is less than the loss of muscle mass relative to the control.
11. The method of claim 7 , wherein the loss of muscle mass in the subject's immobilized limb comprises less than a 10% loss of muscle mass relative to the subject's baseline measurement of muscle mass prior to a period of immobilization.
12. The method of claim 7 , 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 is administered orally.
13. A method of treatment comprising administering to a human subject (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 human subject has an immobilized limb, and
wherein the amount of (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 administered is sufficient to reduce the rate of loss of Type I muscle fibers in immobilized muscle tissue of the subject relative to a control,
wherein the measure of the rate of loss of Type I muscle fibers in the immobilized muscle tissue 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.
14. The method of claim 13 , 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 is administered orally.