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Encouraging first results of GABAergic interneurons for focal epilepsy

Presented By
Dr David Spencer, Oregon Health & Science University in Portland, USA
AAN 2023

Preliminary results of 2 participants in a first-in-human study of GABAergic interneurons (NRTX-1001) for drug-resistant focal epilepsy were presented at the AAN 2023 meeting in Boston. Both participants had over 90% seizure reduction since surgery.

NRTX cells are embryonic stem cells differentiated into pallial medial ganglionic eminence (MGE)-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.

A first-in-human phase 1/2 clinical trial (NCT05135091) investigates whether implantation of human NRTX-1001 can lead to seizure control in drug-resistant mesial temporal lobe epilepsy (MTLE). Participants receive immunosuppression starting 1 week prior to surgery, which is tapered after 1 year. Treatment consists of a stereotactic one-time injection along the long axis of the hippocampus with intra-operative MRI imaging. The trial follows is a 2-stage design: in the open-label phase 1, a total of 10 participants receive low- or high-dosed 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. Patients are between 16 and 65 years of age, have focal seizures clinically defined as temporal lobe epilepsy (TLE), and have failed to achieve seizure control on at least 2 ant-seizure medications.

Dr David Spencer (Oregon Health & Science University in Portland, USA), presented the results of the first 2 enrolled patients [1]. The first subject was a 26-year-old male who had seizures since the age of 19. Prior to treatment, he averaged 32 seizures per month. Treatment with 4 anti-seizure medications had previously failed. At 8 months follow-up after cell therapy, this patient had a 93% seizure reduction from baseline and had not had a focal awareness-impaired seizure since the first month.

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

The observed adverse events after surgery were non-serious and of mild severity in both patients. None of the adverse events were deemed related to cell therapy, some to immunosuppression. Dr 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. Session ES1.007, AAN 2023 Annual Meeting, 22–27 April, Boston, USA.


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