A groundbreaking clinical trial is taking a new approach to treat seizures: brain cell transplantation.
Duke is one of the first sites in the United States to treat a patient in this pioneering study, which is evaluating the safety and efficacy of NRTX-1001, an investigational cell product. NRTX-1001 transplantation is being tested in adults with temporal lobe epilepsy, a common cause of drug-resistant seizures.
Duke neurosurgeon and surgical director of the Duke Comprehensive Epilepsy Center, Derek Southwell, MD, PhD, is a principal investigator in this early first-in-human study. Describing standard surgical approaches to treating epilepsy, he says, “Traditionally, our goal has been to identify and eliminate the area of the brain that produces a patient’s seizures. That strategy, by which we remove or thermally ablate the seizure focus, can reduce, or even stop a patient’s seizures. But in some cases, tissue removal or ablation can negatively impact brain functions such as memory, language, or vision.”
The new experimental treatment, by contrast, involves the transplantation of specific human brain cells, called cortical interneurons, into the area that produces seizure activity. In animal studies published 10-15 years ago, Southwell and colleagues showed that transplanted mouse interneurons can survive in the recipient brain and make functional neural connections, or synapses, with recipient cells.
Transplanted interneurons alter and restore neural circuit function in the area where they are grafted, and, in animals, they improve seizures.
In late 2021, following a decade of refinements in cell manufacturing processes and extensive safety and efficacy testing, Neurona Therapeutics, the trial sponsor, received Food and Drug Administration approval to initiate first-in-human studies of NRTX-1001, a human interneuron cell product. A recent publication describes NRTX-1001 and its pre-clinical testing.
In August of 2023, Southwell treated the first patient at Duke (and the fifth in the United States) with this experimental cell therapy. He and his colleagues are now evaluating the patient’s response to the transplant. A woman implanted with NRTX-1001 last year at Oregon Health Sciences University reports becoming nearly seizure-free after treatment.
Contrasting NRTX-1001 transplantation with standard epilepsy surgeries, Southwell says, “As a non-destructive approach, interneuron transplantation could be a way of reducing or stopping seizures without eliminating a part of the brain altogether. In terms of risk-benefit, this restorative strategy of cell transplantation could be more favorable for patients, and it may encourage more people to pursue surgical epilepsy treatment. The purpose of this current trial is to understand whether NRTX-1001 transplantation is safe and effective for use in epilepsy patients.”
Birgit Frauscher, MD, a neurologist who recently joined Duke to lead the Comprehensive Epilepsy Center, is part of this novel study. “Only by pursuing innovative and rigorous trials like this, which break from traditional approaches, can we establish the next treatments for patients with drug-resistant seizures,” she says.
Southwell has contributed to the development of interneuron transplantation from its earliest stages almost 20 years ago. He was recruited to Duke in late 2018 to lead a program in the study of cortical interneurons and cellular approaches to neural circuit repair. In this recent article, he describes pre-clinical studies of interneuron transplantation and summarizes the design of the ongoing first-in-human trial.
Details about the NRTX-1001 trial are available at the Duke Neurosurgery, ClinicalTrials.gov, and Neurona Therapeutics websites.