Mayo Clinic is participating in the first in-human investigation of regenerative therapy for the treatment of drug-resistant epilepsy. The multicenter study will test the safety of implanting interneurons into the hippocampus in patients with the disease. Future studies are planned to investigate the potential for these cells to restore normal excitatory-inhibitory balance.
“This work has the potential to rewrite the care pathway for epilepsy,” says Jonathon J. Parker, M.D., Ph.D., a neurosurgeon at Mayo Clinic in Phoenix/Scottsdale, Arizona, and co-principal investigator of the study at that site. “The concept is that, at a fundamental level, loss of interneurons is seen often in the hippocampus after repeated seizures. We hope that replacing these inhibitory cells can restore the normal excitatory balance and reduce or even eliminate seizures.”
The interneurons are derived from human embryonic stem cells in a way that prevents them from reverting back to stem cells. The therapy involves a single stereotactic intracerebral administration of interneurons into individuals with drug-resistant unilateral mesial temporal lobe epilepsy.
“For years, patients have asked me about stem cell treatment. They say, ‘If there are stem cells for other diseases, couldn’t stem cells fix my epilepsy?’ ” says Amy Z. Crepeau, M.D., a neurologist at Mayo Clinic’s campus in Arizona and co-principal investigator of the study. “It’s exciting now to explore a treatment that might impact seizure mechanisms, not in a way that is destructive to tissue but in a regenerative way.”
Each of Mayo Clinic’s three campuses is a Level 4 Epilepsy Center, the highest designation given by the National Association of Epilepsy Centers. As a major center, Mayo Clinic has the breadth of expertise to cover all aspects of cutting-edge studies.
“Very specific imaging protocols are needed for the MRI-guided cell implantation procedure,” says Justin Cramer, M.D., a neuroradiologist at Mayo Clinic’s campus in Arizona. Yuxiang Zhou, Ph.D., a Mayo Clinic medical physicist, worked with Drs. Parker and Cramer to develop those protocols.
“Medications try to correct the abnormal circuitry pharmacologically. Traditional surgery tries to ablate or disconnect the circuitry, and stimulation therapies try to rehabilitate it,” Dr. Parker says. “Regenerative therapy could be transformative.”
Beyond standard imaging
Mayo Clinic is at the forefront of improving options for the treatment of epilepsy. One particular focus is improved imaging to localize lesions. Mayo Clinic’s protocols go beyond the base specified for a Level 4 Epilepsy Center.
“We routinely perform 7T MRI for our patients,” Dr. Parker says. “We know that around 30% of people deemed nonlesional on 3T MRI are found to have an abnormality on 7T MRI.”
Enhanced clarity
This animation shows a susceptibility-weighted MRI performed at 3T and 7T for the same patient. As the image transitions to 7T, it shows increasing detail — demonstrating many more intracranial veins and overall greater image contrast and decreased noise. Individual layers of cortex can even be perceived.
Dr. Cramer notes that 7T MRI helps overcome the challenge of identifying the often subtle lesions that can cause epilepsy. “7T basically gives you a doubling of everything,” he says. “You get double the spatial resolution, half the noise and greater contrast resolution. The images are sharper and more detailed.”
In addition to using 7T MRI, Mayo Clinic radiologists also perform these advanced imaging procedures:
Magnetoencephalography, which helps target stereo-electroencephalography electrode placement. Mayo Clinic is one of the few centers in the United States to routinely offer this imaging.
Photon-counting CT, which helps surgeons better visualize electrode placement in the brain and is available at a few select centers.
Subtraction ictal SPECT coregistered to MRI (SISCOM), which precisely measures blood flow during seizures and was developed at Mayo Clinic.
Artificial intelligence (AI) is another new tool. Mayo Clinic specialists use machine learning approaches to mine imaging data for improved lesion detection. “Quantitative approaches that augment lesion detection, which we are actively pursuing, are a real advantage to our program,” Dr. Parker says.
“This work has the potential to rewrite the care pathway for epilepsy.” — Jonathan J. Parker, M.D., Ph.D.
In addition to implementing AI-based epilepsy lesion detection, Dr. Cramer also is using AI methods to assess how hippocampal segmentation might be applied to 7T MRI. “We want to learn how we can best translate volumetric data between 3T and 7T,” he says.
Mayo Clinic’s commitment to patient care underlies this embrace of new technology. “Mayo Clinic doesn’t shy away from early adoption of the best equipment,” Dr. Parker says.
Discussing patients’ options
Recent advances have given patients an array of choices for epilepsy treatment. “We take time to discuss these options with individual patients,” Dr. Crepeau says. “It’s not just a checklist. We look at patients’ entire situations to see the best options for them to meet their goals.”
Even patients who don’t feel ready for epilepsy surgery can benefit from referral to a neurosurgeon. Dr. Parker cites three examples:
- Individuals whose seizures persist after trying two medications.
- Individuals whose epilepsy is controlled by medication but whose imaging results show a brain lesion. “Our surgical approaches are very effective at potentially getting patients off all medications and even gaining seizure freedom,” Dr. Parker says.
- Individuals with generalized epilepsy not responding to medical therapy, for whom deep brain stimulation is showing increased efficacy.
“Conversations with patients early in the disease course are very important,” Dr. Parker says. “We want to offer people every appropriate opportunity to treat their seizures. We have to move the field forward.”
For more information
FIH Study of NRTX-1001 Neural Cell Therapy in Drug-Resistant Unilateral Mesial Temporal Lobe Epilepsy. Mayo Clinic.
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