Use of Pramipexole to Treat Amyotrophic Lateral Sclerosis

Abstract

The present invention is directed to compositions comprising pramipexole and the use of such compositions to treat neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). As shown in FIG. 6 B the mean +/− SEM serum 2.3 DHBA levels for the 12 ALS participants decreased significantly after pramipexole treatment.

1 . A method of treating ALS in a patient in need thereof, said method comprising administering to said patient a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a neuroprotectant amount of a tetrahydrobenthiazole having the general structure:  
     
       
         
         
             
             
         
       
     
     wherein R 1 , R 2 , R 3 , and R 4 , are independently selected from the group consisting of H and C 1 -C 3  alkyl.  
   
   
       2 . The method of  claim 1  wherein R 1 , R 2  and R 4 , are H and R 3  is C 1 -C 3  alkyl.  
   
   
       3 . The method of  claim 1  wherein said tetrahydrobenthiazole is pramipexole.  
   
   
       4 . The method of  claim 3  wherein greater than 90% of the pramipexole in said composition is R(+) 2-amino-4,5,6,7-tetrahydro-6-propylaminobenzathiazole.  
   
   
       5 . The method of  claim 1  wherein the bioelectric potential (ΔΨ) across mitochondrial membranes of cells with impaired mitochondrial energy production is enhanced by the tetrahydrobenthiazole.  
   
   
       6 . The method of  claim 5  wherein said tetrahydrobenthiazole is pramipexole.  
   
   
       7 . The method of  claim 6  wherein greater than 90% of the pramipexole compound is R(+) 2-amino-4,5,6,7-tetrahydro-6-propylaminobenzathiazole.  
   
   
       8 . The method of  claim 1  effective to reduce oxidative stress  
     
       
         
         
             
             
         
       
     
   
   
       9 . The method of  claim 8  wherein said tetrahydrobenthiazole is pramipexole.  
   
   
       10 . The method of  claim 9  wherein said pramipexole is R(+) 2-amino-4,5,6,7-tetrahydro-6-propylaminobenzathiazole.  
   
   
       11 . The method of  claim 1 , wherein about 3 mg to about 500 mg of tetrahydrobenthiazole is administered daily.  
   
   
       12 . The method of  claim 12 , wherein said tetrahydrobenthiazole is R(+) 2-amino-4,5,6,7-tetrahydro-6-propylaminobenzathiazole.  
   
   
       13 . The method of  claim 13 , wherein between about 3 mg to about 6 mg is administered daily.  
   
   
       14 . The method of  claim 1 , wherein about 30 mg/kg to about 100 mg/kg of tetrahydrobenthiazole is administered per day.  
   
   
       15 . The method of  claim 15 , wherein said tetrahydrobenthiazole is R(+) 2-amino-4,5,6,7-tetrahydro-6-propylaminobenzathiazole.  
   
   
       16 . The method of  claim 1 , wherein said tetrahydrobenthiazole is administered via a route selected from the group consisting of transdermal, topical, oral, intravenous, intramuscular, intra-arterial, intramedullary, intrathecal, intraventricular, subcutaneous, intrapeitoneal, intranasal, enteral, sublingual, and rectal.  
   
   
       17 . The method of  claim 1 , wherein said tetrahydrobenthiazole is administered in a dosage escalation regime.  
   
   
       18 . A dosage formulation kit for administering a tetrahydrobenthiazole, said kit comprising a pharmaceutical composition comprising a tetrahydrobenthiazole, a pharmaceutically acceptable carrier, an applicator, and an instructional material for the use thereof, wherein the tetrahydrobenthiazole has the general structure:  
     
       
         
         
             
             
         
       
     
     wherein R 1 , R 2 , R 3 , and R 4 , are independently selected from the group consisting of H and C 1 -C 3  alkyl.