mTOR Inhibition in Epilepsy: Rationale and Clinical Perspectives.

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Bibliographic Details
Title:	mTOR Inhibition in Epilepsy: Rationale and Clinical Perspectives.
Authors:	Ostendorf, Adam, Wong, Michael
Source:	CNS Drugs. Feb2015, Vol. 29 Issue 2, p91-99. 9p.
Subjects:	Treatment of epilepsy, mTOR protein, Cell communication, Targeted drug delivery, Neurotransmitters, Ion channels
Abstract:	Despite a large number of available medical options, many individuals with epilepsy are refractory to existing therapies that mainly target neurotransmitter or ion channel activity. A growing body of preclinical data has uncovered a molecular pathway that appears crucial in many genetic and acquired epilepsy syndromes. The mammalian target of rapamycin (mTOR) pathway regulates a number of cellular processes required in the growth, metabolism, structure, and cell-cell interactions of neurons and glia. Rapamycin and similar compounds inhibit mTOR complex 1 and decrease seizures, delay seizure development, or prevent epileptogenesis in many animal models of mTOR hyperactivation. However, the exact mechanisms by which mTOR inhibition drives decreased seizure activity have not been completely determined. Nonetheless, these preclinical data have led to limited use in humans with epilepsy due to tuberous sclerosis complex and polyhydramnios, megalencephaly, and symptomatic epilepsy with promising results. Currently, larger controlled studies are underway using mTOR inhibitors in individuals with tuberous sclerosis complex and intractable epilepsy. [ABSTRACT FROM AUTHOR]
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Database:	Psychology and Behavioral Sciences Collection

Description
Abstract:	Despite a large number of available medical options, many individuals with epilepsy are refractory to existing therapies that mainly target neurotransmitter or ion channel activity. A growing body of preclinical data has uncovered a molecular pathway that appears crucial in many genetic and acquired epilepsy syndromes. The mammalian target of rapamycin (mTOR) pathway regulates a number of cellular processes required in the growth, metabolism, structure, and cell-cell interactions of neurons and glia. Rapamycin and similar compounds inhibit mTOR complex 1 and decrease seizures, delay seizure development, or prevent epileptogenesis in many animal models of mTOR hyperactivation. However, the exact mechanisms by which mTOR inhibition drives decreased seizure activity have not been completely determined. Nonetheless, these preclinical data have led to limited use in humans with epilepsy due to tuberous sclerosis complex and polyhydramnios, megalencephaly, and symptomatic epilepsy with promising results. Currently, larger controlled studies are underway using mTOR inhibitors in individuals with tuberous sclerosis complex and intractable epilepsy. [ABSTRACT FROM AUTHOR]
ISSN:	11727047
DOI:	10.1007/s40263-014-0223-x