Everolimus (RAD001) Therapy for Epilepsy in Patients With Tuberous Sclerosis Complex (TSC)

Tuberous sclerosis complex (TSC) is a genetic disorder with an incidence at birth of 1 in
6000. This disorder is characterized by the development of benign tumors in multiple organ
systems, including the brain. The primary neurological manifestations of TSC are epilepsy,
mental retardation and autism. Epilepsy is most common, occurring in 80-90% of patients,
and often the seizures are severe, unremitting, and uncontrolled by current anticonvulsant
medications. It is generally accepted that the seizures arise from cortical and subcortical
tubers and surrounding tissue in the brain. These tubers are caused by mutations in the
tumor suppressor genes TSC1 or TSC2. The protein products of these genes, hamartin and
tuberin, act as negative regulators of the PI3K/PKB(Akt)/mTOR signaling pathway that
regulates cell growth and proliferation Everolimus is an immunosuppressant drug that also
inhibits mTOR signaling and is capable of reversing aberrant mTOR-dependent effects that
occur when hamartin or tuberin are absent or defective. Thus, we hypothesize that drugs
like everolimus may be therapeutically useful for the treatment of refractory epilepsy in
patients with TSC.