Cell Stem Cell: Transplanting Neurons for Epilepsy Treatment Achieves a New Breakthrough
Researchers from Neurona Therapeutics, in collaboration with the University of California, San Francisco, have published a research paper in the Cell Stem Cell journal titled "Human Pallial MGE-type GABAergic Interneuron Cell Therapy for Chronic Focal Epilepsy."
The study demonstrates that the transplantation of medial ganglionic eminence GABAergic interneurons (MGE-pIN) derived from human embryonic stem cells (hESC) into the hippocampus of a mouse model with mesial temporal lobe epilepsy (MTLE) reliably eliminates epileptic seizures and significantly extends their lifespan.
These preclinical research results provide support for the first human phase I/II clinical trial using MGE-pIN cell therapy to treat drug-resistant MTLE, which is currently underway by Neurona and the California Institute for Regenerative Medicine (CIRM).
Pallial GABAergic interneurons (pIN) are a major source of inhibitory neurons in the neocortex and hippocampal regions, making cell therapy based on pINs a potential means to rectify the pathological physiology of epilepsy foci.
Tissue obtained from patients with mesial temporal lobe epilepsy (MTLE) revealed the absence of medial ganglionic eminence (MGE) pIN, and necessary gene mutations in MGE-pIN were discovered in various developmental epilepsy conditions.
In collaboration, Neurona and the University of California, San Francisco researchers developed, characterized, and tested a cell therapy known as hMGE-pIN using clinical-grade human embryonic stem cells (hESC).
With a single injection of hMGE-pIN into the hippocampus of a mouse model with chronic mesial temporal lobe epilepsy (MTLE), most mice experienced a cessation of epileptic seizures over time and a longer lifespan. Transplanted interneurons were locally diffused, achieved functional integration, and remained long-term. This also significantly reduced the diffusion of dentate granule cells, a pathological hallmark of MTLE. The therapeutic effects were dose-dependent and exhibited a broad treatment range, with no adverse reactions observed.
These preclinical research results led to FDA approval of Neurona's NRTX-1001 therapy. Currently, Neurona is conducting human phase I/II clinical trials for NRTX-1001 to treat drug-resistant mesial temporal lobe epilepsy (MTLE). The objective of this clinical trial is to verify the safety (number of adverse events) and effectiveness (frequency of epileptic seizures) of injecting inhibitory neurons into the brains of drug-resistant MTLE patients.
In this clinical trial, the research team will assess the safety, tolerability, evidence of neuronal cell survival, and local inflammation (using brain magnetic resonance imaging) two years after transplantation, as well as its impact on epilepsy symptoms. Treated patients will be monitored for over ten years, with quarterly follow-up phone calls.
More information: Bershteyn, Marina, et al. "Human pallial MGE-type GABAergic interneuron cell therapy for chronic focal epilepsy." Cell Stem Cell 30.10 (2023): 1331-1350.