CHICAGO — A one-time dose of a novel cell therapy appeared safe and produced months-long seizure control in patients with bilateral drug-resistant mesial temporal lobe epilepsy (MTLE), according to early results from an ongoing phase 1/2 trial.

The therapy may eventually be an option for patients with bilateral seizure generation who are ineligible for other interventions, said study investigator Peter C Warnke, MD, professor of neurosurgery, neurology and pediatrics, and chief of stereotactic and functional neurosurgery at The University of Chicago, Chicago.

While this is still an early phase study, the findings are “very promising,” Warnke told Medscape Medical News.

“This therapy actually targets, for the first time, the underlying biology of epilepsy. It comes with very little morbidity, doesn’t destroy any tissue, and doesn’t require implantation of hardware,” Warnke said.

The findings were presented on April 22 at the American Academy of Neurology (AAN) 2026 Annual Meeting.

A Fine Balance

About 80% of temporal lobe epilepsy — the most common form of focal-onset epilepsy — is MTLE, which arises from the inner portion of the temporal lobe. Most cases involve the hippocampus.

There are no surgical options for patients with bilateral MTLE. “You can’t ablate or resect both hippocampi because that causes profound cognitive side effects,” Warnke said.

“The only thing you can do right now is put electrodes in and stimulate, which does not lead to seizure freedom, but seizure reduction.”

The new therapy targets the “fundamental concept” of epilepsy — that is that the condition arises when the “very fine and delicate balance” between excitatory and inhibitory signals in the brain is disrupted and shifts toward excitation, causing spontaneous neuronal activity, Warnke said.

The medial ganglionic eminence (MGE), a critical structure during brain development, is the predominant source of inhibitory neurons that secrete the neurotransmitter gamma-aminobutyric acid (GABA).

GABAergic cortical interneurons from the MGE are critical for regulating the excitability of cortical circuits. The idea is to restore the balance and prevent seizures by implanting cells that secrete GABA.

Researchers have developed a cortical MGE-type GABAergic interneuron cell therapy candidate, NRTX-1001. The cells are derived from human stem cells and matured into interneurons.

These are very mature interneurons — not stem cells anymore, said Warnke.

The phase 1/2 study is evaluating intra-hippocampal administration of NRTX-1001 in adults with bilateral drug-resistant MTLE.

The phase 1/2 study is evaluating intra-hippocampal administration of NRTX-1001 in adults with bilateral drug-resistant MTLE.

One-Time Treatment

The current analysis included eight young adults (median age, 27.5 years), the majority of whom were White individuals, with drug-resistant focal seizures originating from the hippocampus and a median epilepsy duration of 12.1 years. All but one participant had hippocampal sclerosis, a known cause of epilepsy, Warnke said.

Participants received immunosuppression to support allograft persistence, starting preoperatively and tapering after 1 year.

Guided by imaging, surgeons deliver a single dose of cells directly into seizure foci within the hippocampus. “The goal is to infuse the entire hippocampus with cells,” Warnke said.

This is followed immediately by a magnetic resonance imaging scan to confirm placement. The therapy requires only a single injection.

Placement is confirmed immediately with an MRI scan.

The therapy is designed as a one-time treatment, with evidence from animal studies suggesting the transplanted cells can survive long term, Warnke said.

Participants are followed quarterly to monitor adverse events (AEs) and seizure frequency and to collect EEG, imaging, and neuropsychological data.

The primary endpoint is 1-year safety. The secondary endpoint is seizure frequency at months 7-12 post-administration.

Median reduction in disabling seizures was 64% at 4-6 months (n = 4) and 65% at 7-9 months (n = 2). Both the 50% and 75% responder rates were 50%.

One patient achieved seizure freedom and remained seizure-free and was off immunosuppression for more than 12 months, Warnke reported.

Quality of life, assessed using the Quality of Life in Epilepsy scale, showed no deterioration, Warnke said. At 6 and 12 months, scores improved by a minimally important difference of five points.

The most common AE was nausea (50%), followed by fatigue, headache, and oropharyngeal pain (all 37.5%), then falls, cough, and rash.

These events were mild-to-moderate and were likely related to the year-long immunosuppression, not the surgery or the cell therapy, Warnke reported.

Two participants experienced serious AEs, which were also unrelated to the therapy, he added, noting that neither immunosuppression nor the procedure itself were implicated.

Encouraging Early Results

Researchers are gathering information on neurocognitive and other outcomes, but these analyses are not yet complete, said Warnke.

An ongoing open-label phase 1/2 trial is evaluating intra-hippocampal administration of the cells in adults with unilateral drug-resistant MTLE.

Warnke described the results as encouraging and his team expects to begin enrolling patients in a pivotal, prospective, randomized, sham-controlled phase 3 trial in the second half of this year, pending FDA approval.

An independent expert said the early findings are promising but should be interpreted cautiously.

Nevertheless, although the sample size is small, the results to date are very encouraging, said Sasha Alick-Lindstrom, MD, associate professor of neurology at the University of Texas Southwestern Medical Center, Dallas, who co-chaired the AAN session featuring the research.

Interneuron cell transplantation represents a genuinely novel approach, and the absence of deterioration — along with signals of clinical improvement and better quality of life — is very encouraging, she said.

She added that she is looking forward to seeing the data from the planned phase 3 sham-controlled trial.

The study is supported by Neurona Therapeutics. Warnke reported receiving compensation for serving as a Consultant for Medtronic and for serving as an Expert Witness for Kline Specter.

Alick-Lindstrom reported being the principal investigator at UT Southwestern Medical Center for Neurona’s Phase 1/2 Clinical Trial of NRTX-1001 Nerve Cell Therapy in Drug-Resistant Unilateral Mesial Temporal Lobe Epilepsy.