Investigate whether implantation of human GABAergic interneurons (NRTX-1001) can lead to seizure control in drug-resistant mesial temporal lobe epilepsy (MTLE).

Implantation of human cortical-type GABAergic interneurons in the hippocampus of mice with kainate-induced mesiotemporal sclerosis can control focal seizures (Priest et al., 2021, AES poster 1.091), with over two-thirds of the cell-treated animals becoming seizure-free for the duration of the 9-month study without producing lethargy, memory deficits, or other dose-limiting toxicities. The interneuron cell therapy also reduced hippocampal damage and increased animal survival. Interneuron cell therapy offers a novel approach to the potential treatment of human focal epilepsy.

This is a first-in-human Phase I/II clinical trial (NCT05135091). Subjects have unilateral MTLE with hippocampal sclerosis and focal seizures refractory to drug treatment. Testing includes EEG, imaging, tests of memory, mood, and assessment of visual fields. Subjects receive immunosuppression beginning 1 week prior to surgery tapering after 1 year. Cells are implanted via stereotactic injection along the long axis of the hippocampus with intra-operative MRI imaging.

Two subjects have been enrolled and had cell implantation. Data are reported as of 31Dec2022. There have been no serious adverse effects. Subject #1 is 6 months out from dosing. Baseline seizure frequency was 32/month; post-surgery, there has been a >90% seizure reduction and the subject has been free of focal awareness-impaired seizures since month 1. Subject #2 is 2 months out from dosing and has moved from a baseline seizure frequency of 14/month to one reported seizure since surgery.

This first-in-human study of NRTX-1001 GABAergic interneurons for focal epilepsy is underway, and preliminary results are encouraging.