Clinical Update: NRTX-1001 GABAergic Interneuron Cell Therapy for Bilateral Drug-resistant Focal Epilepsy
Peter Warnke1, Naoum Issa1, Kevin Graber2, Vivek Buch3, David Spencer4, Kim Burchiel4, Nathan Fountain5, Shayan Moosa5, Gautam Banik6, Marina Bershteyn6, Alessandro Bulfone6, Brianna Feld6, Luis Fuentealba6, John Hixson6, Manher Joshi6, Ji-Hye Jung6, Tia Kowal6, Sonja Kriks6, Rose Larios6, Ngoc Minh Le6, Seonok Lee6, Sheri Madrid6, Yves Maury6, Catherine Priest6, Cory Nicholas6
1University of Chicago, 2Stanford University Medical Center, 3Stanford University, 4Oregon Health & Science University, 5University of Virginia, 6Neurona Therapeutics
Objective:
To present results from an ongoing open-label, multicenter Phase 1/2 trial (NCT06422923) evaluating NRTX-1001 cell therapy for the treatment of seizures due to bilateral drug-resistant mesial temporal lobe epilepsy (MTLE).
Background:
GABAergic cortical interneurons from the medial ganglionic eminence (MGE) are critical for regulating the excitability of cortical circuits. We developed a cortical MGE-type GABAergic interneuron cell therapy candidate, NRTX-1001, derived from human pluripotent stem cells for single-dose administration into seizure foci. NRTX-1001 demonstrated encouraging results in an ongoing open-label Phase 1/2 clinical trial (NCT05135091) evaluating intra-hippocampal administration of cells in 18 adults with unilateral drug-resistant MTLE. NRTX-1001 has been well-tolerated, with preliminary efficacy data showing a substantial reduction in seizure frequency and no decline in neurocognitive performance.
Design/Methods:
This Phase 1/2 study investigates bilateral intra-hippocampal administration of NRTX-1001 in 10 adults with bilateral drug-resistant MTLE. Immunosuppression is administered to promote allograft persistence, beginning preoperatively and tapering after year one. Quarterly visits monitor adverse events (AEs), seizure frequency, EEG, imaging, and neuropsychological metrics. The primary endpoint is one-year safety; the secondary endpoint is seizure frequency at months 7-12 post-administration.
Results:
The first bilateral MTLE subject treated with NRTX-1001 achieved seizure freedom and continues to be seizure-free at 6 months (time of abstract submission). These data, and data for additional subjects treated, will be presented at the conference.
Conclusions:
One-time NRTX-1001 administration offers the potential for durable seizure control in bilateral drug-resistant MTLE. NRTX-1001 cell therapy may represent an option for patients with bilateral seizure generation who are not eligible for, or interested in, resection, ablation, or neurostimulator implantation surgeries.
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