The present invention relates to methods of treating various neurodevelopmental and neuropsychiatric diseases which employ inhibition of the mTOR pathway, particularly using mTOR kinase inhibitors. It is based, at least in part, on extensive phenotypic characterization of a knock-out mouse model of Caspr2, the murine ortholog of CNTNAP2, which indicate that the mechanism via which CNTNAP2 deficits lead to neuropsychiatric disorders is overactivation of the mTOR pathway. Accordingly, the present invention provides for methods of treating subjects suffering from neurodevelopmental and/or neuropsychiatric disorders comprising administering, to the subject, an agent that inhibits the mTOR pathway. In particular non-limiting embodiments, the inhibitor of the mTOR pathway is a mTOR kinase inhibitor such as, but not limited to, WYE125132 and analogous compounds. In a non-limiting subset of embodiments, subjects may be tested to determine whether they have a copy number variation or mutation in CNTNAP2 and where such a copy number variation or mutation is present treatment with a mTOR pathway inhibitor may be initiated.
THERAPEUTIC TARGETING OF THE MTOR PATHWAY IN NEURODEVELOPMENTAL AND NEUROPSYCHIATRIC DISEASE