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

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.

KEY WORDS:

• Seizures
• epilepsy
• epileptogenesis
• mTOR
• rapamycin
• everolimus
• tuberous sclerosis
• traumatic brain injury

Financial and competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.