Treatment of muscular disorders with combinations of RXR agonists and thyroid hormones
The present specification provides methods of treating a muscular disorder with a combination of a RXR agonist and a thyroid hormone.
1. A method of treating a muscular disorder, the method comprising administering to an individual in need thereof a therapeutically effective amount of a RXR agonist and a thyroid hormone, wherein the RXR agonist has the structure of Formula II
wherein R is H or lower alkyl of 1 to 6 carbon; or a pharmaceutically acceptable salt thereof;
wherein administration of the RXR agonist and the thyroid hormone treats the muscular disorder in the individual more effectively than either the RXR agonist or the thyroid hormone alone; and
wherein the muscular disorder is cardiac muscle infarction.
2. The method according to claim 1 , wherein is the RXR agonist is a selective RXR agonist comprising 3,7-dimethyl-6(S),7(S)-methano, 7-[1,1,4,4-tetramethyl-1,2,3,4-tetrahydronaphth-7-yl]2(E),4(E) heptadienoic acid.
3. The method according to claim 1 , wherein the RXR agonist is 3,7-dimethyl-6(S),7(S)-methano, 7-[1,1,4,4-tetramethyl-1,2,3,4-tetrahydronaphth-7-yl]2(E),4(E) heptadienoic ethyl ester.
4. The method according to claim 1 , wherein the thyroid hormone is thyroxine.
5. The method according to claim 1 , wherein the therapeutically effective amount of an ester of the RXR agonist having the structure of Formula II is about 0.001 mg/day to about 1000 mg/day.
6. The method according to claim 1 , wherein the therapeutically effective amount of the RXR agonist is about 0.001 mg/day to about 1000 mg/day.
7. The method according to claim 1 , wherein the therapeutically effective amount of the RXR agonist is about 1 mg/day to about 100 mg/day.
8. The method according to claim 4 , wherein the dose of the thyroxine is about 12.5 μg/day to about 250 μg/day.
9. The method according to claim 1 , wherein the RXR agonist is administered by nasal administration.
10. The method according to claim 1 , wherein the RXR agonist is administered orally.
11. The method according to claim 1 , wherein the RXR agonist and the thyroid hormone are both administered substantially simultaneously.
12. The method according to claim 1 , wherein the RXR agonist and the thyroid hormone are administered on different schedules.
13. The method according to claim 1 , wherein the thyroid hormone is administered orally.
14. The method according to claim 1 , wherein the combination of the RXR agonist and the thyroid hormone is beneficial by effecting heart muscle protection or regeneration in vivo.
15. A method of treating a muscular disorder, the method comprising administering to an individual in need thereof a therapeutically effective amount of 3,7-di methyl-6(S),7(S)-methano, 7-[1, 1,4,4-tetramethyl-1,2,3,4-tetrahydronaphth-7-yl]2(E),4(E) heptadienoic acid, and thyroxine; and wherein administration of the combination reduces the severity of the muscular disorder in the individual by slowing or stopping progression, and/or inducing or hastening repair or regeneration of the affected muscle or muscles, wherein administration of the RXR agonist and the thyroxine treats the muscular disorder in the individual more effectively than either the RXR agonist or the thyroxine alone, wherein the muscular disorder is cardiac muscle infarction.