L-methylfolate treatment for psychiatric or neurologic disorders

Abstract

Provided herein are methods of treating neuropsychiatric disorders or improving the symptoms associated therewith administering a medical food, such as L-methylfolate, to a subject having the disorder. The neuropsychiatric disorder may be an autism spectrum disorder or attention deficit disorder with or without hyperactivity (ADD/ADHD). The L-methylfolate may be administered as an adjunct to other therapeutic agents effective to treat the disorder. The subject preferably may be a child and also may have a single nucleotide polymorphism in the MTHFR gene associated with reduced expression of MTHFR enzyme. Also provided is a method of increasing the de novo synthesis of neurotransmitters in vivo by transporting a methyl-donating compound across the blood-brain barrier in a subject.

1 . A method of increasing in vivo de novo synthesis of neurotransmitters associated with the folate cycle, comprising:
 transporting across a blood brain barrier a compound effective to donate methyl groups for methionine biosynthesis and concurrent de novo synthesis of the neurotransmitters.   
     
     
         2 . The method of  claim 1 , wherein oral administration of the compound effects transport across the blood brain barrier. 
     
     
         3 . The method of  claim 1 , wherein the compound is L-methylfolate or a pharmacological salt or hydrate thereof. 
     
     
         4 . The method of  claim 2 , wherein the L-methylfolate is administered to a subject diagnosed with an autism spectrum disorder or attention deficit disorder with or without hyperactivity. 
     
     
         5 . The method of  claim 4 , wherein the subject has a single nucleotide polymorphism in the MTHFR gene. 
     
     
         6 . The method of  claim 4 , wherein the L-methylfolate is administered at an initial dose of about 2.5 mg to about 15 mg. 
     
     
         7 . The method of  claim 6 , wherein the dose is increased during a period of about 7 days to about 30 days from initial administration. 
     
     
         8 . The method of  claim 1 , wherein the neurotransmitters are one or more of dopamine, norepinephrine or serotonin. 
     
     
         9 . A method for treating one or both of a psychiatric or neurologic disorder in a subject, comprising:
 administering a pharmacological amount of a compound effective to supplement one or both of a serum folate deficiency or suspected cerebrospinal deficiency in the subject thereby treating the psychiatric or neurologic disorder(s).   
     
     
         10 . The method of  claim 9 , further comprising:
 administering one or more other agents effective to treat the psychiatric or neurologic disorder(s).   
     
     
         11 . The method of  claim 10 , wherein the other agent(s) is administered concurrently or consecutively with the compound. 
     
     
         12 . The method of  claim 9 , wherein the compound is a medical food. 
     
     
         13 . The method of  claim 12 , wherein the medical food is L-methylfolate or a pharmacological salt or hydrate thereof. 
     
     
         14 . The method of  claim 9 , wherein a dose of the compound is a daily dose of about 2.5 mg to about 15 mg. 
     
     
         15 . The method of  claim 14 , wherein the dose is escalated during a period of about 7 days to about 30 days from initial administrations. 
     
     
         16 . The method of  claim 9 , wherein the psychiatric and/or neurologic disorder is an autism spectrum disorder, attention deficit disorder with or without hyperactivity or a combined subtype thereof or comorbid anxiety with or without oppositional or conduct disorders. 
     
     
         17 . The method of  claim 9 , wherein the subject has a single nucleotide polymorphism in the MTHFR gene associated with reduce expression of MTHFR enzyme. 
     
     
         18 . The method of  claim 9 , wherein the subject is a child. 
     
     
         19 . A method for improving behavioral or neurologic symptoms associated with an autism spectrum disorder and/or an attention deficit disorder with or without hyper-activity in a subject, comprising:
 administering to the subject a dose of L-methylfolate that is increased as the behavioral or neurological symptoms associated with the disorder or disorders decrease thereby improving the symptoms associated with the disorder or disorders.   
     
     
         20 . The method of  claim 19 , further comprising:
 administering one or more other agents effective to treat the disorder or disorders.   
     
     
         21 . The method of  claim 20 , wherein the other agent(s) is administered concurrently or consecutively with the dose of L-methyfolate. 
     
     
         22 . The method of  claim 19 , wherein an initial administered dose is a single dose of about 7 days to about 30 days from initial administration. 
     
     
         23 . The method of  claim 19 , wherein the dose is increased during a period of about 7 days to about 30 days from initial administration. 
     
     
         24 . (canceled) 
     
     
         25 . The method of  claim 19 , wherein the subject has a single nucleotide polymorphism in the MTHR gene associated with reduced expression of MTHFR enzyme. 
     
     
         26 . The method of  claim 19 , wherein the subject is a child.