First-in-Human Trial of NRTX-1001 GABAergic Interneuron Cell Therapy for Focal Epilepsy - Updated Clinical Trial Results
John Hixson1, David Spencer2, Kim Burchiel2, Harish Babu3, Robert Beach3, Jerry Shih4, Sharona Ben-Haim4, Rebecca O'Dwyer5, Sepehr Sani5, Derek Southwell6, Matthew Luedke7, David Blum1, Gautam Banik1, Marina Bershteyn1, Alessandro Bulfone1, Brianna Feld1, Holly Finefrock1, Luis Fuentealba1, Ji-Hye Jung1, Tia Kowal1, Sonja Kriks1, Rose Larios1, Seonok Lee1, Sheri Madrid1, Yves Maury8, Catherine Priest1, Sergei Shevchuk1, Manher Joshi1, Cory Nicholas1
1Neurona Therapeutics, 2OHSU, 3SUNY Syracuse, 4UC San Diego Health, 5Rush University Medical Center, 6Duke University, 7Duke University Hospital Dept. of Neurology, 8Neurona therapeutics
Objective:
To present updated findings from a first-in-human, open-label study of NRTX-1001, an allogeneic GABAergic interneuron therapy, for unilateral drug-resistant temporal lobe epilepsy with mesial temporal sclerosis (NCT05135091).
Background:
NRTX-1001 is an investigational GABAergic interneuron product derived from human pluripotent stem cells. Preclinical studies demonstrated that hippocampal transplantation significantly reduces seizure frequency in a mouse kainic acid model of focal epilepsy (Bershteyn et.al., Cell Stem Cell 30:1-20, 2023). Between June 2022 and May 2024, ten subjects were enrolled in the ongoing first-in-human study designed to assess the safety and efficacy of NRTX-1001.
Design/Methods:
Adults participants with drug-resistant unilateral TLE with mesial temporal sclerosis were administered NRTX-1001 via stereotactic surgery into the hippocampal head and body with intraoperative imaging. Immunosuppression was initiated one week prior to the procedure and is scheduled for tapering after one year. The primary endpoint is safety, with secondary endpoints of seizure frequency, neuroimaging, EEG, cognitive function, and visual fields at one-year post-treatment.
Results:
As of July 2024, five subjects in the low-dose cohort were at least 6 months post-treatment, with two subjects completing 24 and 19 months of follow-up. The low-dose cohort demonstrated an 82% reduction in disabling seizure frequency over the 4-6-month post-treatment period, with 80% achieving a ≥50% responder rate. No treatment-related serious adverse events (SAEs) have been reported. For all treated subjects, three non-treatment-related SAEs were observed. These were not determined to be related to the cells, procedure, or immunosuppression. Preliminary cognitive assessments revealed improvements in select measures of memory function for some subjects. Updated results for all subjects will be presented.
Conclusions:
NRTX-1001 administration has been well-tolerated in ten patients with drug-resistant TLE, with preliminary data suggesting significant reductions in seizure frequency and potential cognitive improvements. Unlike current surgical treatment options, NRTX-1001 may provide a non-destructive, cell-based therapeutic approach, potentially providing a restorative option for focal epilepsy.
Disclaimer: Abstracts were not reviewed by Neurology® and do not reflect the views of Neurology® editors or staff.