Combination therapy

Abstract

The present disclosure provides certain combination therapy technologies that are particularly useful for treating one or more diseases, disorders, or conditions that may be related to abnormal metabolism. In some embodiments, provided technologies provides combinations of TCA cycle acids and ketone bodies. In some embodiments, provided technologies provides combinations of TCA cycle acids and other carboxylic acids.

1 - 20 . (canceled) 
     
     
         21 . A pharmaceutical composition comprising a compound of formula I-a; 
       
         
           
           
               
               
           
         
         or a salt thereof, wherein R′ is C 3 -C 7  linear alkyl. 
       
     
     
         22 . The composition of  claim 21 , wherein the compound is 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         23 . A method of treating a disease, disorder, or condition, the method comprising providing to a subject having a disease, disorder, or condition a composition comprising a pharmaceutically effective amount of a compound of formula I-a; 
       
         
           
           
               
               
           
         
         or a salt thereof, wherein R′ is C 3 -C 7  linear alkyl. 
       
     
     
         24 . The method of  claim 23 , wherein the compound is 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         25 . The method of  claim 23 , wherein the disease, disorder or condition is related to abnormal metabolism. 
     
     
         26 . The method of  claim 23 , wherein the disease, disorder or condition is an energetic disorder. 
     
     
         27 . The method of  claim 26 , wherein the energetic disorder is selected from the group consisting of refractory epilepsy, propionic acidemia (PA), methylmalonic acidemia (MMA), a long chain fatty acid oxidation disorder, succinyl-CoA lyase deficiency, and pyruvate carboxylase deficiency. 
     
     
         28 . The method of  claim 23 , wherein the disease, disorder or condition is a neurologic disease. 
     
     
         29 . The method of  claim 28 , wherein the neurologic disorder is selected from the group consisting of Huntington's disease, Parkinson's disease, and Alzheimer's disease. 
     
     
         30 . The method of  claim 23 , wherein the disease, disorder or condition is a cancer. 
     
     
         31 . The method of  claim 23 , wherein the disease, disorder or condition is a pain or fatigue disease. 
     
     
         32 . The method of  claim 31 , wherein the pain or fatigue disease is selected from the group consisting of fibromyalgia and chronic fatigue syndrome. 
     
     
         33 . The method of  claim 23 , wherein the disease, disorder or condition is a muscular dystrophy. 
     
     
         34 . The method of  claim 33 , wherein the muscular dystrophy is selected from the group consisting of Duchenne's muscular dystrophy and Becker's muscular dystrophy. 
     
     
         35 . The method of  claim 23 , wherein the disease, disorder or condition is a mitochondrial myopathy. 
     
     
         36 . The method of  claim 35 , wherein the mitochondrial myopathy is selected from the group consisting of mitochondrial encephalomyopathy, lactic acidosis, stroke-like syndrome (MELAS), and myoclonic epilepsy and ragged-red fibers (MERRF). 
     
     
         37 . The method of  claim 23 , wherein the disease, disorder or condition is a mitochondrial associated disease. 
     
     
         38 . The method of  claim 37 , wherein the mitochondrial associated disease is related to POLG mutation. 
     
     
         39 . The method of  claim 23 , wherein the disease, disorder or condition is a mitochondrial respiratory chain deficiency. 
     
     
         40 . The method of  claim 39 , wherein the mitochondrial respiratory chain deficiency is selected from the group consisting of glutaric acidemia type 1 and glutaric acidemia type 2.