Inhibitory Interneuron Cell Therapy Reduces Seizures in First 2 Patients With MTLE


Data from a phase 1/2 clinical trial of NRTX-1001 were presented at the ISSCR 2023 Annual Meeting.

New 1-year data from the phase 1/2 clinical trial (NCT05135091) of Neurona Therapeutics’ inhibitory interneuron cell therapy NRTX-1001 has demonstrated seizure reductions in treated participants with drug-resistant unilateral mesial temporal lobe epilepsy (MTLE).1

These data were presented at the International Society for Stem Cell Research (ISSR) 2023 Annual Meeting, by Cory Nicholas, PhD, chief executive officer and cofounder, Neurona.

“Patient 1 has reached the 1-year post treatment endpoint and has achieved a >95% overall monthly seizure reduction, including elimination of all seizure events since the seventh month post-administration of NRTX-1001,” David Blum, MD, chief medical officer, NeuronaTherapeutics, said in a statement.2 “In addition, this patient has shown improved memory performance on cognitive tests. We continue to enroll patients in the first cohort of the study and look forward to providing additional updates later this year.”

NRTX-1001 is a medial ganglionic eminence pallial type GABAergic interneuron cell therapy derived from human pluripotent stem cells that has previously shown disease-modifying activity in a mouse mode of MTLE. The study is evaluating a single, MRI-guided administration of NRTX-1001 cells into the hippocampus across 12 sites in the US.1 The first phase is evaluating safety and tolerability in a dose-expansion scheme, with 2 cohorts of 5 patients (eligible for lobectomy) each receiving different doses of NRTX-1001. The primary endpoint is the frequency of adverse events (AEs) at 1 year and the secondary endpoint is assessing efficacy by measuring seizure frequency and responder rate at 1 year after treatment. Other endpoints will assess neurocognitive outcomes, EEG, imaging, and blood biomarkers, anti-seizure drug dose reductions. The second stage of the study will randomize 20 patients to receive active cell transplant and 10 to receive a sham transplant.

READ MORE: Focal Epilepsy Cell Therapy Trial Cleared to Expand

Two patients have been treated in the study so far with no serious AEs, structural abnormalities, or inflammation as seen on MRI. NRTX-1001 was successfully delivered on target and the data safety monitoring board has cleared the study to continue enrolling patients with both dominant and non-dominant lobe MTLE. Both patients had previously been treated with clobozam, lacosamide, levetiracetam and lorazepam anti-seizure medications (ASMs). The first patient had also previously received oxcarbazepine and the second patient had also received midozolam.

The first participant is a 26-year-old male patient that had an average of 32 seizures per month in the 6 prior months with a 7-year history of seizures with right mesial temporal sclerosis (MTS). Nine months after NRTX-1001 administration, he had a 95% reduction in seizures and was able to reduce 2 ASMs (1-year data are still being analyzed). The second participant is a 59-year-old female patient that had an average of 14 seizures per month in the 6 prior months with a 9-year history of seizures with right MTS. Six months after NRTX-1001 administration, she had a 94% overall seizure reduction, specifically with a 100% reduction in focal aware seizures and a 57% reduction in focal impaired awareness seizures. Neurocognitive outcome measures increased at 6 and 9 months after treatment in participant 1 and select scores numerically increased by 6 months in participant 2.1

“Both patients entered the clinical trial with significant seizure activity, impaired cognition, and suboptimal quality of life. They were candidates for lobectomy or ablation surgery to remove the epileptic seizure-generating temporal lobe, albeit with an associated risk of causing further, irreversible cognitive deficits. Instead, they courageously chose to be first to receive NRTX-1001 cell therapy. Although our clinical investigation is ongoing in additional patients, it is gratifying to witness the first 2 patients achieving seizure-relief without additional cognitive impairment to date, which supports the therapeutic potential of NRTX-1001," Nicholas added to the statement.2 "We are hopeful that these improvements will continue in the ongoing trial andpossibly provide others living with drug-resistant focal seizures with a non-destructive cell therapy option in the future that does not risk cognitive decline. Relatedly, the NRTX-1001 trial has received clearance from the FDA to expand enrollment to include adults who have MTLE in the verbal memory-dominant lobe and are at greater risk of cognitive decline from a tissue-destructive lobectomy or ablation surgery. We are grateful to the patients, caregivers, and our clinical collaborators for their participation in this first in human clinical study.”

1. Nicholas C. A phase I/II clinical trial of NRTX-1001 HPSC-derived inhibitory interneuron cell therapy for chronic focal epilepsy. Presented at: ISSCR 2023 Annual Meeting.
2. Neurona Therapeutics Presents One-Year Data on the First Patient Treated with NRTX-1001 Cell Therapy in an Ongoing Phase I/II Trial for Drug-resistant Focal Epilepsy. News release. Neurona Therapeutics. June 15, 2023.
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