Authors :
Presenting Author: David Blum, MD – Neurona Therapeutics
Harish Babu, MD, PhD – Neurosurgery – SUNY Syracuse; Robert Beach, MD, PhD – Neurology – SUNY Syracuse; Kim Burchiel, MD – Neurosurgery – Oregon Health Sciences University; David Spencer, MD – Neurology – Oregon Health Sciences University; Andy Adler, PhD – Neurona Therapeutics; Gautam Banik, PhD – Neurona Therapeutics; Alessandro Bulfone, MD – Neurona Therapeutics; Brianna Feld, PhD – Neurona Therapeutics; Holly Finefrock, . – Neurona Therapeutics; Ji-Hye Jung, PhD – Neurona Therapeutics; Rose Larios, PhD – Neurona Therapeutics; Seonok Lee, PhD – Neurona Therapeutics; Sheri Madrid, . – Neurona Therapeutics; Catherine Priest, PhD – Neurona Therapeutics; Sergei Shevchuk, PhD – Neurona Therapeutics; Cory Nicholas, PhD – Neurona Therapeutics
Rationale:
This clinical study is investigating whether one-time implantation of human GABAergic interneurons derived from allogeneic human stem cells (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 nine 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 non-tissue destructive approach to the potential treatment of human focal epilepsy. Methods:
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 one week prior to surgery tapering after one year. Cells are implanted via stereotactic injection along the long axis of the hippocampus with intra-operative MRI imaging. The primary endpoint is safety, and the secondary endpoint is seizure frequency at one year post-implant.Results:
Data are reported as of May 1, 2023 from the first two subjects enrolled in the study and will be updated to November 1 at the meeting. There have been no serious adverse effects. Subject Number 1 is 11 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 one. Subject Number 2 is seven months out from dosing and has had a >90% seizure reduction with a >50% reduction in awareness-impaired seizures. Memory scores are clearly improved for Subject Number 1 and moderately improved for Subject Number 2.Conclusions:
This first-in-human study of NRTX-1001 GABAergic interneurons for focal epilepsy is underway, and preliminary results are encouraging. One-time implantation of NRTX-1001 cells offers the potential for seizure control in patients with MTLE without removal or ablation of brain tissue.Funding:
CIRM TRAN1-11611; CLIN2-13355.