Preliminary results from a first-in-human study of GABAergic interneurons for drug-resistant focal epilepsy show a seizure reduction of over 90% 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 investigates whether implantation of human NRTX-1001 can lead to seizure control for 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. 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 receive 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 aged 16 to 65, have focal seizures clinically defined as temporal lobe epilepsy (TLE), and have failed to achieve seizure control on at least two antiseizure medications.
David Spencer, MD, presented the results of the first enrolled patients (N=2). 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 four 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 three antiseizure medications and averaged 14 seizures a month. At 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 were related to immunosuppression. Dr Spencer said he was excited about the first results of this novel therapy.
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