title: Mammalian target of rapamycin (mTOR) inhibition: potential for antiseizure, antiepileptogenic, and epileptostatic therapy.
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 Furthermore, beneficial effects on seizures are lost when treatment is withdrawn, suggesting that mTOR inhibitors are "epileptostatic" in only stalling epilepsy progression during treatment.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.
authors.affiliation: 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. rytherr@neuro.wustl.edu
authors.forename: Robin C C
authors.initials: RC
authors.lastname: Ryther
authors.forename: Michael
authors.initials: M
authors.lastname: Wong
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000188:drug therapy*; D004195:Disease Models, Animal; D006801:Humans; D012640:Seizures / Q000188:drug therapy*; D015398:Signal Transduction / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D014402:Tuberous Sclerosis / Q000188:drug therapy*
chemical_list: D058570:TOR Serine-Threonine Kinases