Results from a clinical trial have shown that the drug everolimus can reverse the genetic defect associated with tuberous sclerosis complex (TSC).

The study, EXIST-3, showed that everolimus significantly reduced treatment-resistant seizures associated with TSC when used as an adjunctive therapy. “What is exciting and significant about this study is that everolimus targets the genetic mutation responsible for TSC, which is the overactivation of mammalian target of rapamycin (mTOR),” says David Franz, MD, founding director of the Tuberous Sclerosis Clinic at Cincinnati Children’s and senior author of the study. “Therefore, everolimus not only treats the seizures, but every other manifestation of the disease, including autism, cognitive impairment, tumors on vital organs and disfiguring skin tumors. What’s more, it has the potential to treat any other disease where the common thread is overactivation of mTOR, such as genetic brain malformations, epilepsy and autism.”

The Food and Drug Administration approved everolimus, a chemotherapy agent, in 2010 to treat children with brain tumors associated with the disease. Since then, Franz and other tuberous sclerosis experts from around the world have been studying its potential to treat other manifestations of TSC in clinical trials.

Based on the results of the EXIST-3 study, the European Medical Association approved everolimus for the adjunctive treatment of seizures associated with TSC in January 2017, and Franz hopes for Food and Drug Administration approval in the near future. “What we are learning about everolimus is changing the worldwide standard of care for TSC,” he explains. “We will continue to explore other questions about everolimus, such as whether it can be used with other drugs to reverse the intellectual disability associated with TSC.”

Read the abstract

The EXIST-3 study appeared in The Lancet (October 29, 2016). Everolimus is marketed by Novartis, which provided drug and financial support for the study. In addition, several of the study authors are employees of Novartis. The first author of the EXIST-3 study was Jacqueline French, MD, professor of neurology and director of Translational Research & Clinical Trials Epilepsy at NYU Langone’s Comprehensive Epilepsy Center.