Further Studies Could Determine Benefit to Epilepsy Patients Without TSC

A drug originally developed to prevent organ transplant rejection also dramatically reduces seizures in patients with tuberous sclerosis complex (TSC), according to study results posted online in the Annals of Neurology.

The study is the latest to demonstrate the effectiveness of everolimus for TSC patients. Previous studies conducted at Cincinnati Children’s show that everolimus can reduce tumors in the brain and the kidney.

“Everolimus treatment reduced seizure frequency and duration in the majority of TSC epilepsy patients whose seizures previously did not respond to treatment,” says Darcy Krueger, MD, PhD, a pediatric neurologist at Cincinnati Children’s and lead author of the study. “This improvement in seizure control was associated with a better quality of life, and side effects were limited. Work is already underway to confirm these results in a follow-up, phase III clinical study.”

The latest study was conducted in collaboration with a team at Texas Children’s Hospital in Houston.  

“This has been positively life-changing for the patients involved and is nothing short of transformative in the treatment of epilepsy associated with cellular growth disorders, such as TSC,” says Angus Wilfong, MD, director of the epilepsy program at Texas Children’s.  

Everolimus reduced seizure frequency by at least 50 percent in 12 of the 20 study participants. Four patients were free of seizures and seven had at least a 90 percent reduction in seizure frequency. Parents also reported several positive changes in quality of life, including attention, behavior, social interaction and physical restrictions.

Studies in the 1990s traced TSC to defects in two genes, TSC1 and TSC2. When these genes malfunction, cells have higher activity of mTOR, a protein known to trigger uncontrolled tumor cell and blood vessel growth. Everolimus shrinks tumors by inhibiting mTORC1, and it appears to reduce seizures in TSC patients in the same way.

“It is unclear whether the benefit of everolimus in treating epilepsy might extend beyond that observed in TSC,” Krueger says. “mTORC1 has been implicated in genetic and neurodevelopmental syndromes in which epilepsy is prominent and in more common types of epilepsy. Additional clinical trials might tell us whether everolimus would benefit patients with epilepsy not related to TSC.”