Methods of determining response to therapy

A method of determining whether a subject with Fragile X Syndrome or other cognitive disorder will derive a benefit from a metadoxine treatment regimen comprising:

• a) measuring the amount of phosphorylated ERK and Akt protein in a sample derived from the subject;
• b) measuring the total amount of ERK and Akt protein in the sample;
• c) calculating a ratio of the amount of phosphorylated ERK and Akt protein determined in step (a) to the amount of ERK and Akt protein determined in step b);
• and
• d) comparing the calculated ratio of step c) to a calculated ratio measured from a non-diseased subject, wherein when the calculated ratio of step c) is higher than the calculated ratio of non-diseased subject indicates that the subject will derive a benefit from the metadoxine treatment regimen.

A method of monitoring a metadoxine treatment regimen in a subject having Fragile X Syndrome or other cognitive disorder comprising:

• a) measuring the amount of phosphorylated ERK and Akt protein in a first sample from the subject at a first period of time;
• b) measuring the total amount of ERK and Akt protein in the first sample at the first period of time;
• c) calculating a first ratio of the amount of phosphorylated ERK and Akt protein determined in step a) to the amount of total ERK and Akt protein determined in step b);
• d) measuring the amount of phosphorylated ERK and Akt protein in a second sample from the subject at a second period of time;
• e) measuring the total amount of ERK and Akt protein in the second sample at the second period of time;
• f) calculating a second ratio of the amount of phosphorylated ERK and Akt protein determined in step d) to the total amount of ERK and Akt protein determined in step e) to produce a second ratio;
• d) comparing the first ratio to the second ratio.