Treatment of muscular disorders with combinations of rxr agonists and thyroid hormones

Abstract

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 myocytes for subsequent implantation of the myocytes into damaged cardiac muscle to regenerate heart muscle, the method comprising treating myocytes in vitro with an 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. 
       
     
     
         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 combination of RXR agonist and thyroid hormone generates myocytes more effectively than either the RXR agonist or thyroid hormone alone. 
     
     
         5 . The method according to  claim 1 , wherein the thyroid hormone is thyroxine. 
     
     
         6 . The method according to  claim 1 , wherein the thyroid hormone is triiodothyronine. 
     
     
         7 . The method of  claim 1 , wherein the concentration of the RXR agonist is from 0.08 nM to 1 μM. 
     
     
         8 . A method of treating a muscular disorder, the method comprising administering to an individual in need thereof a therapeutically effective amount of 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, 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 thyroid hormone treats the muscular disorder in the individual more effectively that either the RXR agonist or thyroid hormone alone.