First-in-Human Trial of NRTX-1001 GABAergic Interneuron Cell Therapy for Treatment of Focal Epilepsy - Emerging Clinical Trial Results
Harish Babu1, Robert Beach1, Sharona Ben-Haim2, Kim Burchiel3, Matthew Luedke4, Rebecca O'Dwyer5, Sepher Sani5, Jerry Shih2, Derek Southwell4, David Spencer3, Gautam Banik6, Marina Bershteyn6, David Blum6, Alessandro Bulfone6, Brianna Feld6, Holly Finefrock6, Luis Fuentealba6, John Hixson6, Victoria Hosford6, Ji-Hye Jung6, Tia Kowal6, Sonja Kriks6, Rose Larios6, Seonok Lee6, Sheri Madrid6, Yves Maury6, Catherine Priest6, Kiril Shevchuk6, Sergei Shevchuk6, Cory Nicholas6
1SUNY Syracuse, 2UCSD, 3OHSU, 4Duke, 5Rush, 6Neurona Therapeutics
Objective:
To present the early results of a first-in-human clinical study of allogeneic GABAergic interneuron transplantation for unilateral drug-resistant temporal lobe epilepsy (TLE; NCT05135091)
Background:
NRTX-1001 is an investigational GABAergic interneuron product derived from human pluripotent stem cells. In pre-clinical testing, hippocampal transplantation of NRTX-1001 improved spontaneous seizure phenotypes in a mouse kainic acid model of focal epilepsy with hippocampal sclerosis (Bershteyn et.al., Cell Stem Cell 30:1-20, 2023). Between June, 2022 and August, 2023, 5 subjects were enrolled in an ongoing open-label study of NRTX-1001 transplantation.
Design/Methods:
Study subjects are adults with drug-resistant, unilateral TLE with mesial temporal sclerosis. NRTX-1001 cells were surgically transplanted into the head and body of the diseased hippocampus using intra-operative MRI. Immunosuppression was initiated 1 week prior to NRTX-1001 transplantation and will be tapered after 1 year. Study endpoints are safety (primary endpoint) and seizure frequency (secondary) at 1 year post-implant. Other endpoints include assessments of EEG, neuroimaging, cognitive performance, and visual fields.
Results:
As of October 2023, subjects are 15, 11, 2, 1, and 1 months post-treatment (MPT) with NRTX-1001. There have been no serious adverse events. Subject #1 (15 MPT) has experienced >90% seizure reduction and has been free of awareness-impaired seizures since 1 MPT. Subject #2 (11 MPT) has also experienced >90% seizure reduction, with >50% reduction in awareness-impaired seizures. Both subjects have exhibited quantitative improvements in select measures of memory function. Updated results for all subjects will be presented at the meeting.
Conclusions:
NRTX-1001 transplantation was safely performed in 5 patients with drug-resistant TLE. Preliminary results at approximately 1 year (2 subjects) suggest NRTX-1001 transplantation may improve seizure control and memory dysfunction. In contrast to current surgical treatments (e.g., resection and laser ablation), NRTX-1001 could provide a non-destructive and functionally restorative approach to treating focal epilepsy.