Tuberous sclerosis complex as a model disease for developing new therapeutics for epilepsy

Expert Rev Neurother. 2016;16(4):437-47. doi: 10.1586/14737175.2016.1151788. Epub 2016 Feb 29.

Abstract

An unmet need in the treatment of epilepsy has been targeted therapies that prevent the onset or progression of seizures in the susceptible individual. We have no treatments that target the process of epileptogenesis, through which the genetically predisposed or injured brain becomes capable of generating unprovoked, recurrent seizures. Tuberous Sclerosis Complex (TSC) is a multiorgan disorder caused by a defect in the mTOR (mechanistic/mammalian target of rapamycin) pathway. Epilepsy is a prominent feature of TSC, with seizures often occurring after the diagnosis of TSC has already been made. The mTOR pathway has been studied in animal models, with evidence suggesting that downstream effectors may contribute to the mechanisms leading to seizure generation, making the mTOR pathway an attractive candidate for potentially novel and rational antiepileptogenic therapies.

Keywords: Seizures; epilepsy; epileptogenesis; everolimus; mTOR; rapamycin; traumatic brain injury; tuberous sclerosis.

Publication types

  • Review

MeSH terms

  • Animals
  • Anticonvulsants / therapeutic use*
  • Epilepsy / drug therapy*
  • Epilepsy / etiology*
  • Humans
  • Immunosuppressive Agents / therapeutic use
  • Signal Transduction / drug effects
  • Sirolimus / therapeutic use
  • Tuberous Sclerosis / complications*

Substances

  • Anticonvulsants
  • Immunosuppressive Agents
  • Sirolimus