An experimental neural cell therapy is safe and led to greater than 90% reduction in seizures in two patients with drug-resistant mesial temporal lobe epilepsy (MTLE) in the first-in-human test of the novel therapy.
“It is notable that the early significant seizure reduction observed in this study appears to be durable in these first two patients treated with a single administration of NRTX-1001,” principal investigator Robert Beach, MD, PhD, said in a news release.
“It is also encouraging that the first patient has been free from disabling seizures from the second month on and has shown improved memory performance on multiple cognitive tests, as memory problems can be an issue for individuals with drug-resistant MTLE,” said Beach, chief of epilepsy and professor of neurology, at SUNY Upstate Medical University, Syracuse, New York.
The findings will be presented April 24 at the American Academy of Neurology (AAN) 2023 Annual Meeting.
Restorative Not Destructive
NRTX-1001 therapy (Neurona Therapeutics) is a one-time dose of an injectable suspension of high-purity inhibitory interneurons that secrete the inhibitory neurotransmitter gamma-aminobutyric acid (GABA).
The interneurons are intended to integrate and innervate on-target, providing long-term GABAergic inhibition to repair hyperexcitable neural networks.
Preclinical work in animal models of epilepsy has provided strong support for both the safety and the efficacy of boosting inhibition in the seizure focus using implanted human inhibitory interneurons.
This therapy is “potentially restorative instead of just destructive, like epilepsy surgery,” study investigator David Spencer, MD, professor of neurology and director of the Comprehensive Epilepsy Center, Oregon Health & Science University in Portland, said during a press briefing.
In the first two patients, the cells were implanted in the seizure focus using MRI guidance through a tiny opening in the back of the skull. The patients recovered overnight and went home the next day.
The first patient had a 9-year history of drug-resistant epilepsy and was averaging 30 seizures per month at baseline. Testing confirmed that the seizures were coming from a single focus on the right temporal lobe. The implant was uncomplicated, and the cells were delivered to the seizure focus on target.
To date, there have been no serious or unexpected adverse events from the implant. At 9 months of follow-up the patient has had a 93% reduction in seizures overall and is free of all seizures causing impairment of awareness, “which was the most debilitating seizure type for this patient,” Spencer noted.
Studies of brain metabolism in the area of the implant have shown favorable markers of increased inhibition and decreased inflammation. Cognitive testing at 6 months showed no worsening of memory function or cognition. And, in fact, there were some mild improvements, he said.
The second patient had an 8-year history of drug-resistant epilepsy, averaging 14 focal seizures per month at baseline. Testing also confirmed seizure onset in a single focus in the right temporal lobe and the cells were again implanted without complication on target.
Five months after treatment, the patient has had a 94% reduction in seizures and no serious adverse events.
“Hot Off the Press”
Epilepsy affects about 3.5 million people in the United States. About two thirds of people with epilepsy get good control of their seizures using anti-seizure medication.
For seizures that are uncontrolled with medication, identifying the seizure focus and removing it surgically can often result in seizure freedom in a high proportion of patients. But not all patients are candidates for epilepsy surgery, and for those who can have it the surgery itself carries some risks, including diminished cognition and memory.
“While these are still early days, we’re encouraged by the positive safety findings so far, and the early seizure responses” with neural cell therapy, Spencer told reporters.
Given the positive results in the first two patients, additional patients will be treated “with careful safety review all along the way. This is going to be rolling out over the next several years,” Spencer said. Patient recruitment is underway at epilepsy centers across the United States.
Briefing moderator Natalia Rost, MD, MPH, chair of the AAN science committee, said, “This is a true example of emerging science. It’s literally hot off the press” and the preliminary results are “very promising.”
Rost, chief of the stroke division at Mass General in Boston, noted that this type of cell therapy implant is “very novel and representative of where the field is moving, when no traditional solutions exist for common neurological problems.”
The study was sponsored by Neurona Therapeutics and funded in part by the California Institute for Regenerative Medicine. Beach and Spencer report no relevant financial relationships. Several investigators are employees of Neurona Therapeutics. Rost reports no relevant financial relationships.
American Academy of Neurology (AAN) 2023 Annual Meeting: Abstract 1175. To be presented April 24, 2023.
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