Methods for treating multiple sclerosis

Abstract

Methods for increasing oligodendrocyte survival are disclosed. The methods of the invention are useful for the treatment of Multiple Sclerosis.

1 . A method for increasing survival of oligodendrocytes, comprising administering an effective amount of a deprenyl compound to a patient such that survival of oligodendrocytes is increased.  
     
     
         2 . The method of  claim 1 , wherein the deprenyl compound is represented by the structure:  
       
         
           
           
               
               
           
         
       
       in which 
 R 1  is hydrogen, alkyl, alkenyl, alkynyl, aralkyl, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, or aryloxycarbonyl;  
 R 2  is hydrogen or alkyl;  
 R 3  is a single bond, alkylene, or —(CH 2 ) n —X—(CH 2 ) m ;  
 in which X is O, S, or N-methyl; m is 1 or 2; and n is 0,1, or 2;  
 R 4  is alkyl, alkenyl, alkynyl, heterocyclyl, aryl or aralkyl; and  
 R 5  is alkylene, alkenylene, alkynylene and alkoxylene; and  
 R 6  is C 3 -C 6  cycloalkyl or —CCH; or  
 R 2  and R 4 -R 3  are joined to form, together with the methine to which they are attached, a cyclic or polycyclic group;  
 and pharmaceutically acceptable salts thereof.  
 
     
     
         3 . The method of  claim 2 , wherein R 1  is a group that can be removed in vivo.  
     
     
         4 . The method of  claim 2 , wherein R 1  is hydrogen.  
     
     
         5 . The method of  claim 2 , wherein R 1  is alkyl.  
     
     
         6 . The method of  claim 2 , wherein R 1  is methyl.  
     
     
         7 . The method of  claim 2 , wherein R 2  is methyl.  
     
     
         8 . The method of  claim 2 , wherein R 3  is methylene.  
     
     
         9 . The method of  claim 2 , wherein R 4  is aryl.  
     
     
         10 . The method of  claim 2 , wherein 4 is phenyl.  
     
     
         11 . The method of  claim 2 , wherein R 5  is methylene.  
     
     
         12 . The method of  claim 2 , wherein R 5  is  
         —C≡CH  
     
     
         13 . The method of  claim 2 , wherein the deprenyl compound is represented by the structure:  
       
         
           
           
               
               
           
         
       
       in which 
 R 1  is hydrogen, alkyl, alkenyl, alkynyl, aralkyl, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, or aryloxycarbonyl;  
 R 2  is hydrogen or alkyl;  
 R 3  is a bond or methylene; and  
 R 4  is aryl or aralkyl; or  
 R 2  and R 4 -R 3  are joined to form, together with the methine to which they are attached, a cyclic or polycyclic group;  
 and pharmaceutically acceptable salts thereof.  
 
     
     
         14 . The method of  claim 2 , wherein the deprenyl compound is represented by the structure:  
       
         
           
           
               
               
           
         
       
       in which 
 R 2  is hydrogen or alkyl;  
 R 3  is a bond or methylene; and  
 R 4  is aryl or aralkyl; or  
 R 2  and R 4 —R 3  are joined to form, together with the methine to which they are attached, a cyclic or polycyclic group; and  
 R 5  is alkylene, alkenylene, alkynylene and alkoxylene;  
 and pharmaceutically acceptable salts thereof.  
 
     
     
         15 . The method of  claim 2 , wherein the deprenyl compound is represented by the structure:  
       
         
           
           
               
               
           
         
       
       in which 
 R 1  is hydrogen, alkyl, alkenyl, alkynyl, aralkyl, alkylcarbonyl, arylcarbonyl, alkoxycarbonyl, or aryloxycarbonyl;  
 A is a substituent independently selected for each occurrence from the group consisting of halogen, hydroxyl, alkyl, alkoxyl, cyano, nitro, amino, carboxyl, —CF 3 , or azido;  
 n is 0 or an integer from 1 to 5;  
 and pharmaceutically acceptable salts thereof.  
 
     
     
         16 . The method of  claim 1 , wherein said patient is a human.  
     
     
         17 . The method of  claim 1 , wherein said deprenyl compound is (−)-desmethyldeprenyl.  
     
     
         18 . A method for inhibiting Multiple Sclerosis, comprising administering to a patient an effective amount of a deprenyl compound such that Multiple Sclerosis is inhibited.  
     
     
         19 . The method of  claim 18 , wherein said deprenyl compound is (−)-desmethyldeprenyl.  
     
     
         20 . The method of  claim 18 , wherein said patient is a human.  
     
     
         21 . A method for increasing oligodendrocyte survival in vitro, comprising contacting oligodendrocytes with an effective amount of a deprenyl compound such that oligodendrocyte survival is increased.  
     
     
         22 . A method for increasing oligodendrocyte survival in a patient, comprising contacting an oligodendrocyte with a deprenyl compound such that oligodendrocyte survival increases.  
     
     
         23 . The method of  claim 22 , wherein said patient is a human.  
     
     
         24 . The method of  claim 23 , wherein the deprenyl compound is (−)-desmethyldeprenyl.  
     
     
         25 . The method of  claim 24 , wherein the (−)-desmethyldeprenyl is administered transdermally to the patient.