The role of mTOR inhibitors in preventing epileptogenesis in patients with TSC: Current evidence and future perspectives

Epilepsy Behav. 2019 Feb:91:94-98. doi: 10.1016/j.yebeh.2018.05.039. Epub 2018 Jun 22.

Abstract

Tuberous sclerosis complex (TSC) is one of the most common genetic causes of epilepsy. Mutations in the TSC1 or TSC2 genes lead to the dysregulation of the mechanistic target of rapamycin (mTOR) pathway. This mTOR pathway hyperactivation is associated with several processes resulting in epileptic conditions. The occurrence of seizures and their treatment outcomes seem to play a crucial role in cognitive and behavioral developments in patients with TSC. Mechanistic target of rapamycin inhibitors have been proven to be effective in epilepsy treatment in individuals with TSC. Specifically, because of their disease-modifying mechanism of action, they have the capability to prevent epileptogenesis in patients with TSC. This article will provide an overview of the current evidence of and delineate future perspectives for mTOR inhibitors and their role in preventing epileptogenesis.

Keywords: Personalized medicine; Preventive treatment; Refractory epilepsy; Seizure; TSC; mTOR inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anticonvulsants / pharmacology
  • Anticonvulsants / therapeutic use*
  • Epilepsy / drug therapy*
  • Epilepsy / etiology
  • Epilepsy / metabolism
  • Forecasting
  • Humans
  • Sirolimus / pharmacology
  • Sirolimus / therapeutic use
  • TOR Serine-Threonine Kinases / antagonists & inhibitors*
  • TOR Serine-Threonine Kinases / metabolism
  • Treatment Outcome
  • Tuberous Sclerosis / complications
  • Tuberous Sclerosis / drug therapy*
  • Tuberous Sclerosis / metabolism

Substances

  • Anticonvulsants
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Sirolimus