Autoimmune Disorder Treatment Using RXR Agonists

Abstract

The present specification provides RXR agonist compounds, compositions comprising such RXR agonists, and methods using such compounds and compositions to treat an autoimmune disorder, inflammation associated with an autoimmune disorder and/or a transplant rejection as well as use of such RXR agonists to manufacture a medicament and use of such compounds and compositions to treat an autoimmune disorder, inflammation associated with an autoimmune disorder and/or a transplant rejection.

1 . A method of treating Alzheimer's Disease, the method comprising the step of administering to an individual in need thereof a therapeutically effective amount of a RXR agonist, having the structure of formula V 
       
         
           
           
               
               
           
         
       
       where R 4  is lower alkyl of 1 to 6 carbons; B is —COOH or —COOR 8  where R 8 is lower alkyl of 1 to 6 carbons, and the configuration about the cyclopropane ring is cis, and the configuration about the double bonds in the pentadienoic acid or ester chain attached to the cyclopropane ring is trans in each of the double bonds, or a pharmaceutically acceptable salt of the compound, and wherein the individual does not have cachexia. 
     
     
         2 . The method according to  claim 1 , wherein the RXR agonist is a compound having the structure of formula XII: 
       
         
           
           
               
               
           
         
       
       wherein R is H, lower alkyl or 1 to 6 carbons, or a pharmaceutically acceptable salt of the compound. 
     
     
         3 . The method according to  claim 2 , 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 acid, and has the structure of formula XXIX: 
       
         
           
           
               
               
           
         
       
     
     
         4 . The method according to  claim 1 , wherein the therapeutically effective amount is about 0.01 mg/kg/day to about 100 mg/kg/day. 
     
     
         5 . The method according to  claim 1 , wherein the therapeutically effective amount is about 0.1 mg/kg/day to about 10 mg/kg/day. 
     
     
         6 . The method according to  claim 1 , wherein as a result of the treatment, at least one symptom selected from inflammation, fatigue, dizziness, malaise, irritability, anxiety, and depression is reduced. 
     
     
         7 . The method according to  claim 3 , wherein the RXR agonist is a salt or an ester of formula XXIX.