Anti-convulsant Agents: Everolimus

Abstract

Everolimus is the only first-generation analogue of rapamycin being licensed for systemic antiproliferative treatment and seizure control in tuberous sclerosis complex (TSC).With its potential to maintain dose-dependent inhibition of the anabolic cellular mammalian target of rapamycin (mTOR) complex 1 (mTORC1), everolimus can induce long-lasting systemic growth control of tumors including SubEpendymal Giant cell Astrocytoma (SEGA) in TSC. In addition, everolimus can contribute substantially to seizure control in complicated symptomatic epilepsies in TSC most likely working as an antiepileptogenic (i.e., addressing the underlying molecular pathophysiology) instead of anti-convulsant agent (inhibition of neuronal hyperexcitability regardless of cause). Up to now, it remains unclear, whether and to what extent this mTOR inhibitor may be able to preserve cognitive potential and neurodevelopment in TSC and whether this arises either by its basic TORC1 inhibition or secondarily by its antiepileptogenic activity. M-TOR inhibitors have a wide range and a high incidence of side effects that must be taken into account. Fortunately in majority, these tend to be mild or transient and typically able to be managed effectively. Frequent interactions with other medications commonly used in this population have to be regarded, either inducing or inhibiting their own (everolimus/sirolimus) metabolism. Given a proper indication and a thorough handling of risk factors, long-termeffectiveness and long-termtolerability are durable, not interfering unpredictably with infectious risks, somatic growth, sexual maturation, and fertility. Further clinical experience has to be gathered concerning optimal dosing regiments, adverse effects and placement of everolimus in combined therapies of TSC: Further research will elucidate the properties of everolimus in the therapeutic armamentarium of TSC. Further, basic research is underway to define best therapeutic intervention in the context of early, diseasemodifying, preventive therapy, including standard treatment (e.g., vigabatrin), everolimus, or the succeeding next generation of mTOR inhibitors.