Triheptanoin for the treatment of glucose transport 1 deficiency

Abstract

Provided are methods for treating GLUT1 and related brain energy deficiencies comprising administering odd-carbon fatty acid sources, e.g., C5 or C7 fatty acid sources, and related compositions.

1 . A method of treating a GLUT1 deficiency or a GLUT1 deficiency-associated condition or disorder in a human subject in need thereof, comprising administering to the subject an odd-chain fatty acid source. 
     
     
         2 . The method of  claim 1 , where the subject has a disease-associated mutation in at least one SLC2A1 gene. 
     
     
         3 . The method of  claim 2 , where the subject has experienced one or more GLUT1 deficiency-associated conditions selected from seizures, dystonic movements, developmental delay, acquired microcephaly, spasticity, ataxia, and paroxysmal exertion-induced dyskinesia. 
     
     
         4 . The method of  claim 1 , where the subject has hypoglycorrhachia without hypoglycemia. 
     
     
         5 . (canceled) 
     
     
         6 . The method of  claim 1 , where the subject is diagnosed with decreased 3-O-methyl-D-glucose uptake in erythrocytes. 
     
     
         7 . The method of  claim 1 , where the subject has cerebral fluoro-deoxy-glucose positron emission tomography (PET) findings characterized by diffuse hypometabolism of the cerebral cortex and regional hypometabolism of the cerebellum and thalamus. 
     
     
         8 . The method of  claim 1 , where the odd-chain fatty acid source is administered as a unit dosage of about 2-150 grams. 
     
     
         9 . (canceled) 
     
     
         10 . (canceled) 
     
     
         11 . The method of  claim 1 , where the odd-chain fatty acid source provides at least about 30-35% of the total calories in the diet of the subject. 
     
     
         12 . The method of  claim 1 , where the odd-chain fatty acid source is administered at about 1 to about 10 grams/kg/24 hours, about 1 to about 5 grams/kg/24 hours, or about 1 to about 2 grams/kg/24 hours. 
     
     
         13 . The method of  claim 1 , where the odd-chain fatty acid source is administered three times a day, twice a day, or once per day. 
     
     
         14 . The method of  claim 1 , where the odd-chain fatty acid source is administered for one month, two months, six months, twelve months, or eighteen months. 
     
     
         15 . (canceled) 
     
     
         16 . The method of  claim 1 , where the odd-chain fatty acid is administered as part of a ketogenic diet. 
     
     
         17 . (canceled) 
     
     
         18 . (canceled) 
     
     
         19 . (canceled) 
     
     
         20 . (canceled) 
     
     
         21 . The method of  claim 1 , where the odd-chain fatty acid is administered in combination with an anti-seizure medication. 
     
     
         22 . The method of  claim 1 , where the odd-chain fatty acid source comprises triheptanoin or a derivative thereof 
     
     
         23 . (canceled) 
     
     
         24 . The method of  claim 1 , where the administration provides a statistically significant therapeutic effect for the treatment of the GLUT1 deficiency or the GLUT1 deficiency-associated condition or disorder. 
     
     
         25 . The method of  claim 1 , comprising detecting the level of one or more Krebs cycle intermediates in the subject, and determining a treatment regimen based on an increase or decrease in the level of one or more Krebs cycle intermediates. 
     
     
         26 . The method of  claim 1 , comprising detecting the level of one or more Krebs cycle intermediates or derivatives in the subject, wherein an increase or decrease in the level of one or more Krebs cycle intermediates or derivatives compared to a predetermined standard level is predictive of the treatment efficacy. 
     
     
         27 . The method of  claim 1 , comprising detecting the level of one or more ketone bodies in the subject treated and determining a treatment regimen based on an increase or decrease in the level of one or more ketone bodies. 
     
     
         28 . The method of  claim 1 , comprising detecting the level of one or more ketone bodies in the subject, wherein an increase or decrease in the level of one or more ketone bodies compared to a predetermined standard level is predictive of the treatment efficacy. 
     
     
         29 . (canceled) 
     
     
         30 . (canceled) 
     
     
         31 . (canceled) 
     
     
         32 . (canceled) 
     
     
         33 . (canceled) 
     
     
         34 . A method of treating or preventing diseases of the brain affecting energy metabolism in a subject, comprising administering to the subject an effective amount of triheptanoin, where the administration of triheptanoin restores mitochondrial energy function and net biosynthesis through anaplerosis. 
     
     
         35 . (canceled) 
     
     
         36 . (canceled) 
     
     
         37 . (canceled) 
     
     
         38 . (canceled)