Abstracts

First-in-human Trial of NRTX-1001 Gabaergic Interneuron Cell Therapy for Drug-resistant Focal Epilepsy – Updated Results

Abstract number : 2.244
Submission category : 4. Clinical Epilepsy / 4C. Clinical Treatments
Year : 2024
Submission ID : 774
Source : www.aesnet.org
Presentation date : 12/8/2024 12:00:00 AM
Published date :

Authors :
Presenting Author: John Hixson, MD – Neurona Therapeutics

David Blum, MD – Neurona Therapeutics
Gautam Banik, PhD – Neurona Therapeutics
Marina Bershteyn, PhD – Neurona Therapeutics
Alessandro Bulfone, MD – Neurona Therapeutics
Brianna Feld, Translational Mgr – Neurona Therapeutics
Holly Finefrock, Clinical Operations – Neurona Therapeutics
Luis Fuenteabla, Associate Director – Neurona Therapeutics
Ji Hye Jung, PhD – Neurona Therapeutics
Tia Kowal, PhD – Neurona Therapeutics
Sonja Kriks, PhD – Neurona Therapeutics
Rose Larios, PhD – Neurona Therapeutics
Seonok Lee, PhD – Neurona Therapeutics
Sheri Madrid, VP Operations – Neurona Therapeutics
Yves Maury, PhD – Neurona Therapeutics
Catherine Priest, PhD – Neurona Therapeutics
Sergei Shevchuk, PhD – Neurona Therapeutics
Cory Nicholas, PhD – Neurona Therapeutics
Nadia Agopyan, PhD – Neurona Therapeutics
AJ Manher, MD – Neurona Therapeutics
Robert Beach, MD – SUNY
Harish Babu, MD – SUNY
David Spencer, MD – Oregon Health & Science University
Kim Burchiel, MD – OHSU
Jerry Shih, M.D. – University of California, San Diego
Sharona Ben-Haim, MD – University of California San Diego
Rebecca O'Dwyer, MD – Rush University Medical Center
Sepehr Sani, MD – Rush
Derek Southwell, MD, PhD – Duke University Medical Center
Matthew Luedke, MD – Duke University Medical Center
Kevin Graber, MD – Stanford University
Lesley Kaye, MD – UC Health University of Colorado Hospital
Steven Ojemann, MD – University of Colorado
John Stern, MD – University of California Los Angeles
Itzhak Fried, MD, PhD – David Geffen School of Medicine at UCLA
Ausaf Bari, MD – David Geffen School of Medicine at UCLA
Vivek Buch, MD – Stanford University

Rationale: This study is investigating the safety and efficacy of a one-time administration of NRTX-1001, an investigational, allogeneic GABAergic interneuron cell therapy in drug-resistant unilateral mesial temporal lobe epilepsy. Prior preclinical data demonstrated NRTX-1001 to be safe and effective in mice with kainate-induced mesiotemporal seizures and sclerosis, resulting in 2/3rds of the treated animals becoming seizure-free without lethargy, memory deficits, or dose-limiting toxicities (Priest et al., 2021, AES 1.091).


Methods: In the ongoing open-label Phase 1/2 clinical trial (NCT05135091) in subjects who have unilateral MTLE with hippocampal sclerosis and refractory seizures, Phase 1 has enrolled two dose cohorts of five subjects each. After initiating immunosuppression, NRTX-1001 is administered into the affected hippocampus via stereotactic injection with intra-operative imaging. Immunosuppression is discontinued after the first year. Study procedures include immune monitoring, EEG, brain imaging, and neuropsychological tests. The primary endpoint is safety for one-year post-administration, and the secondary endpoint is impact on seizure frequency between months 7 and 12 post-administration.


Results: Data are reported as of 21 May 2024 for the ten subjects enrolled in the study who have received a single-dose administration of NRTX-1001, which has been well-tolerated to date in all subjects. A single status epilepticus incident of two SAEs was observed in one subject in the low dose cohort and was attributed to their epilepsy. All other adverse events in both dose cohorts have been non-serious. Two subjects from the low dose cohort have discontinued immunosuppression and all reported adverse events for these subjects have resolved.



The five subjects in the low dose cohort are all at least six months post-administration. Median monthly seizure reduction from baseline was 75% for all seizures. 80% of the subjects achieved >50% seizure reduction, and 60% have become free from the most disabling seizures. For the two subjects with the longest observation periods, the median monthly seizure reduction for months 7-12 was 98% for all seizures. Additional updates from both dose cohorts will be presented.



Trial subjects have undergone baseline and follow-up assessments of word retrieval, verbal episodic memory, visuospatial episodic memory, and quality of life. Reliable change indices (RCIs) or minimally important change (MIC) scores were assessed for subjects with least six months of data. No subjects have demonstrated a persistent decline in neuro-cognitive performance, and some subjects have demonstrated significant improvements.


Conclusions: A first-in-human study of NRTX-1001 GABAergic interneurons for focal epilepsy is underway, and the preliminary safety and efficacy results are encouraging. One-time administration of NRTX-1001 cell therapy offers the potential for seizure control in patients with drug-resistant MTLE without removal or ablation of brain tissue.


Funding: Grant support: CIRM TRAN1-11611; CLIN2-13355


Clinical Epilepsy