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Mammalian Target of Rapamycin (mTOR) Inhibition: Potential for Antiseizure, Antiepileptogenic, and Epileptostatic Therapy

  • Epilepsy (CW Bazil, Section Editor)
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Abstract

New epilepsy treatments are needed that not only inhibit seizures symptomatically (antiseizure) but also prevent the development of epilepsy (antiepileptogenic). The mammalian target of rapamycin (mTOR) pathway may mediate mechanisms of epileptogenesis and serve as a rational therapeutic target. mTOR inhibitors have antiepileptogenic and antiseizure effects in animal models of the genetic disease, tuberous sclerosis complex. The mTOR pathway is also implicated in epileptogenesis in animal models of acquired epilepsy and infantile spasms, although the effects of mTOR inhibitors are variable depending on the specific conditions and model. Furthermore, beneficial effects on seizures are lost when treatment is withdrawn, suggesting that mTOR inhibitors are “epileptostatic” in only stalling epilepsy progression during treatment. Clinical studies of rapamycin in human epilepsy are limited, but suggest that mTOR inhibitors at least have antiseizure effects in tuberous sclerosis patients. Further studies are needed to assess the full potential of mTOR inhibitors for epilepsy treatment.

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Acknowledgments

M. Wong receives funding from the National Institutes of Health (R01 NS056872) and the Washington University/Pfizer Biomedical Research Collaboration.

Disclosure

Conflicts of interest: R.C.C. Ryther: has received travel/accommodations/meeting expenses unrelated to activities listed from the American Epilepsy Society; M. Wong: none.

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  1. Department of Neurology and the Hope Center for Neurological Disorders, Washington University School of Medicine, Box 8111, 660 South Euclid Avenue, St. Louis, MO, 63110, USA

    Robin C. C. Ryther & Michael Wong

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Correspondence to Michael Wong.

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Ryther, R.C.C., Wong, M. Mammalian Target of Rapamycin (mTOR) Inhibition: Potential for Antiseizure, Antiepileptogenic, and Epileptostatic Therapy. Curr Neurol Neurosci Rep 12, 410–418 (2012). https://doi.org/10.1007/s11910-012-0276-5

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