Exploring new pathways for treating medication-refractory epilepsy

April 24, 2026

Mayo Clinic researchers are pursuing innovative approaches for the treatment of medication-refractory epilepsy. Some of these efforts aim to avoid resecting brain tissue. Another focus is on developing new ways to monitor brain activity.

"Our ultimate goal is to help patients achieve seizure freedom with therapies that rebuild or support brain tissue," says Katherine H. Noe, M.D., Ph.D., a neurologist at Mayo Clinic in Phoenix/Scottsdale, Arizona. "We still encourage people to consider brain surgery when appropriate to get their seizures under control. But we are always looking for new options that can help people manage their seizures and improve their quality of life."

Mayo Clinic neurologists are participating in multicenter studies of:

Gene therapy for the treatment of medication-refractory mesial temporal lobe epilepsy (TLE).
Stem cell therapy for the same disorder.
Long-term recording of brain activity, as an alternative to electroencephalography (EEG).

The National Association of Epilepsy Centers rates Mayo Clinic's campuses in Arizona, Florida and Minnesota as Level 4 epilepsy centers — providing the highest level of diagnosis and treatment options for people with epilepsy. Cutting-edge epilepsy research is undertaken at each of these campuses.

"Our team of specialists already has mastery of available treatment options. But we always ask what else can we do for people who haven't achieved seizure control," Dr. Noe says. "At Mayo Clinic, we're driven by our patients' needs."

Gene and stem cell therapies

One-third of people with epilepsy don't respond to medication. Over the past decade, new surgical techniques and neuromodulation devices have helped many people with medication-refractory disease. But some patients aren't candidates for these approaches.

Regenerative therapies can potentially provide alternative approaches. The gene therapy study in which Mayo Clinic participates is testing AMT-260. It's a gene therapy designed to block GRIK2 expression, which increases neuronal excitability. "The idea is to help the chemical and electrical circuitry in the brain to function better," Dr. Noe says.

"It's very exciting to think that we might moderate the brain in that way — to change what the brain is capable of doing."

— Katherine H. Noe, M.D., Ph.D.

The stem cell therapy trial involves injecting interneurons into the hippocampus. Loss of interneurons is often seen in the hippocampus after repeated seizures.

"The goal is to use stem cells to essentially support or regrow neuronal connections in such a way that seizures are no longer present," Dr Noe says. "We hope to moderate or even eliminate seizures. It's very exciting to think that we might moderate the brain in that way — to change what the brain is capable of doing."

Capturing rare electrical activity

Epilepsy can be challenging to diagnose when people experience intermittent events that may or may not be seizures. "Patients might have blackouts or periods of confusion that disrupt their lives. But if these events are infrequent, and we test between episodes. We can't determine that it's epilepsy," Dr. Noe says.

EEG can be performed for up to several days. "But we haven't had the ability to monitor for weeks or even years," Dr. Noe says. "That data could help not only with diagnosis but also with seizure prediction."

Mayo Clinic is part of a multicenter trial of a long-term recording device that might provide an alternative to EEG. A fine electrode, implanted under the scalp, records brain activity. An external device worn on the ear, like a hearing aid, measures the recorded signals and transmits the information to a cloud-based data platform.

"The system gives us chronic recording of brain activity in a way that seems to be very well tolerated by patients," Dr. Noe says. "We could measure a patient's brain activity for years."

Long-term data could potentially help with seizure prediction. "Could we get to the point where patients don't necessarily need to take medication or modify their activities every day?" Dr. Noe says. "At some point, neurologists might be able to give patients a 'seizure forecast,' and they could take medication or modify their activities as needed."

Mayo Clinic's multidisciplinary approach underlies the center's commitment to innovative care. "It takes a team to translate all the advances in basic science into patient treatment. We can't do this work in isolation," Dr. Noe says. "As a quaternary referral center, we see a lot of folks who have exhausted all the options out there. That drives us to find new solutions."