Encouraging first results of GABAergic interneurons implants for focal epilepsy

A first-in-human study evaluated the use of GABAergic interneurons (NRTX-1001) for drug-resistant focal epilepsy. Preliminary results of the first 2 participants show that both participants had over 90% seizure reduction since surgery.

NRTX-1001 cells are embryonic stem cells differentiated into pallial medial ganglionic eminence-type GABAergic interneurons. They are post-mitotic and do not proliferate. In mice with kainate-induced mesiotemporal sclerosis, implantation of these cells resulted in 66% of mice being free of focal seizures. The interneuron cell therapy also reduced hippocampal damage and increased survival in these mice.

A first-in-human, phase 1/2 clinical trial (NCT05135091) investigates whether implantation of human NRTX-1001 neural cell therapy can lead to seizure control in drug-resistant mesial temporal lobe epilepsy [1]. Participants receive immunosuppression starting 1 week before surgery and tapered after 1 year. Treatment consists of a stereotactic one-time injection along the long axis of the hippocampus with intraoperative MRI imaging. The trial follows a 2-stage design: in the open-label phase 1, 10 participants receive low- or high-dose treatments. In the double-blind phase 2, 20 participants receive cell implantation and 10 participants sham treatment. The primary endpoint is the incidence of serious or severe adverse events. Key secondary endpoints include a reduction in seizures and responder rate. Participants are between 16 and 65 years of age, have focal seizures clinically defined as temporal lobe epilepsy, and have failed to achieve seizure control on at least 2 anti-seizure medications.

Prof. David Spencer (Oregon Health & Science University, OR, USA) presented the results of the first 2 enrolled participants [1]. The first participant was a 26-year-old man who had had seizures since the age of 19. Before treatment, he averaged 32 seizures per month and treatment with 4 anti-seizure medications had previously failed. At 8 months follow-up after NRTX-1001 cell therapy, the participant had a 93% seizure reduction from baseline and had not had a focal awareness-impaired seizure since the first month.

The second participant was a 59-year-old woman who had had seizures since she was 50, had previously failed on 3 anti-seizure medications, and averaged 14 seizures a month. After 2 months of follow-up after NRTX-1001 cell therapy, she had experienced just 1 seizure.

The observed adverse events after surgery were non-serious and of mild severity in both participants. None of the adverse events were deemed related to cell therapy, some to immunosuppression. Prof. Spencer said he was excited about the first results of this novel therapy.

1. First-in-human trial of NTRX-1001 GABAergic interneuron cell therapy for treatment of focal epilepsy - emerging clinical trial results. ES1.007, AAN 2023 Annual Meeting, 22–27 April, Boston, USA.

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Posted on 26 June 202317 May 2024