Neurodegenerative disorders and methods of treatment and diagnosis thereof

Abstract

This invention relates to compositions and methods for the therapy and diagnosis of neurodegenerative or neuromuscular disorders. More particularly, this invention relates to use of anaplerotic agents for treating, preventing, or delaying the onset of a neurodegenerative or neuromuscular disorder.

1 . A method of treating an animal with a neurodegenerative and/or neuromuscular disease, disorder or condition, wherein said method includes the step of administering a therapeutically effective amount of one or more anaplerotic agents to said animal, to thereby treat the neurodegenerative and/or neuromuscular disease, disorder or condition in said animal. 
     
     
         2 . (canceled) 
     
     
         3 . The method of  claim 1 , wherein the neurodegenerative and/or neuromuscular disease, disorder or condition is a motor neuron disease (MND). 
     
     
         4 . The method of  claim 3 , wherein the MND is amyotrophic lateral sclerosis (ALS), primary lateral sclerosis (PLS), progressive muscular atrophy (PMA), progressive bulbar palsy (PBP), pseudobulbar palsy, or spinal muscular atrophy (SMA). 
     
     
         5 . The method of  claim 3 , wherein the MND is ALS. 
     
     
         6 . The method of  claim 1 , wherein the one or more anaplerotic agents are selected from the group consisting of glutamate, glutamine, pyruvate and one or more precursors of propionyl-CoA. 
     
     
         7 . The method of  claim 6 , wherein the one or more precursors of propionyl-CoA are selected from the group consisting of an uneven chain fatty acid, a triglyceride, a C5 ketone body, a phospholipid, a branched chain amino acid and combinations thereof. 
     
     
         8 . The method of  claim 7 , wherein the triglyceride is one or more compounds of Formula I: 
       
         
           
           
               
               
           
         
         wherein 
         R 1 , R 2  and R 3  are independently selected from alkyl, alkenyl or alkynyl. 
       
     
     
         9 . The method of  claim 8 , wherein R 1 , R 2  and R 3  are independently selected from C 1  to C 20  alkyl, alkenyl or alkynyl. 
     
     
         10 . The method of  claim 9 , wherein R 1 , R 2  and R 3  are the same and are selected from the group consisting of C 5 , C 7 , and C 9  alkyl. 
     
     
         11 . The method of  claim 9 , wherein the compound of Formula I is selected from tripentanoin, triheptanoin and trinonanoin. 
     
     
         12 . The method of  claim 11 , wherein the compound is triheptanoin. 
     
     
         13 . The method of  claim 1 , wherein the one or more anaplerotic agents are provided to the animal in an amount comprising at least about 5% of the dietary caloric intake for the animal. 
     
     
         14 . The method of  claim 13 , wherein the one or more anaplerotic agents are provided to the animal in an amount comprising at least about 20% of the dietary caloric intake for the animal. 
     
     
         15 . The method of  claim 14 , wherein the one or more anaplerotic agents are provided to the animal in an amount comprising at least about 30% of the dietary caloric intake for the animal. 
     
     
         16 . The method of  claim 15 , wherein the one or more anaplerotic agents are provided to the animal in an amount comprising at least about 35% of the dietary caloric intake for the animal. 
     
     
         17 . The method of  claim 1 , wherein the animal is an adult animal. 
     
     
         18 . The method of  claim 1 , wherein the animal is a mammal. 
     
     
         19 . The method of  claim 18 , wherein the mammal is a human. 
     
     
         20 . The method of  claim 1 , wherein the therapeutically effective amount of one or more anaplerotic agents is administered orally. 
     
     
         21 - 37 . (canceled)