Treatment shows promise in reducing seizures
Neurologists and neurosurgeons believe they can help patients who have uncontrolled seizures with regenerative cell therapy implants.
Explaining how this works is Robert Beach, MD, PhD, who treated a patient -- one of the first two who tried it -- and saw seizures reduced by more than 90%. Beach is a professor of neurology and chief of epilepsy at Upstate.
The new treatment is from Neurona Therapeutics, a San Francisco-based biotherapeutics company.
Beach discusses the early results of an ongoing clinical trial of a single dose of a new regenerative cell therapy called NRTX-1001, which is being evaluated in people with drug-resistant mesial temporal lobe epilepsy, or MTLE, at Upstate and other top epilepsy centers around the U.S.
This represents a potential solution to a high unmet need as these patients have few options besides destructive removal of brain tissue which has a risk of memory impairment and other side effects.
Neurona Therapeutics is developing NRTX-1001, an off-the-shelf human regenerative cell therapy. The cells are delivered as a one-time dose, directly into an area of the brain where the seizures originate, which is the hippocampus in people with MTLE. These human interneurons are intended to integrate and from connections to other nerve cells, providing long-term GABA-mediated inhibition to repair hyper-excitable neural networks.
The patients treated so far have gone home the day after their surgery, returning to the study center for periodic assessments. Initially they take immunosuppressants to give NRTX-1001 time to engraft, but with their doctor’s supervision can come off these drugs after the first year. The data demonstrate greater than 90% reduction in seizure frequency in the first and second patient at nine and five months post-treatment, respectively. In addition, neuropsychological testing suggests an improvement in memory in the first patient after NRTX-1001 administration.
Host Amber Smith: Upstate Medical University in Syracuse, New York invites you to be "The Informed Patient" with a podcast that features experts from Central New York's only academic medical center. I'm your host, Amber Smith. Neurologists and neurosurgeons believe they can help patients who have uncontrolled seizures with regenerative cell therapy implants. And the biotherapeutics company behind this new treatment says the first two patients to try it have seen their seizures reduced by more than 90%. One of those patients was treated at Upstate, and today I'm talking with one of the patient's physicians, Dr. Robert Beach. He's a professor of neurology and chief of epilepsy at Upstate. Welcome to "The Informed Patient," Dr. Beach.
Robert Beach, MD, PhD: Oh, thank you very much, Amber.
Host Amber Smith: Now Neurona Therapeutics is the company behind this new treatment, and it has a national clinical trial underway. Data from the first two patients was presented at the American Academy of Neurology this spring. What can you tell us about how these patients are doing?
Robert Beach, MD, PhD: So, to start off, the very first patient in the world was our patient here, who received the cells 11 months ago. He's done very well, as has the other patient who's had them.
Host Amber Smith: He was having about 30 seizures a month, the patient here. And he has had an average of around one a month over the last several months. The patient in Oregon also had a similar improvement, although not exactly the same.
So it sounds like really substantial improvement.
Robert Beach, MD, PhD: Oh, yes. Really more than we anticipated even.
Host Amber Smith: So this regenerative cell therapy implants, these are being tried as a treatment for someone with epilepsy that's resistant to medication. Is that right?
Robert Beach, MD, PhD: Yes. And a very specific class of those patients, because we're talking about putting a very tiny amount of cells in a very specific place. And one of the best known and characterized sources of seizures that are intractable in humans is those that come from the hippocampus or the medial part of the temporal lobe.
Those have traditionally been treated first with medicine. Usually about a third of them are not controlled with whatever medicines in combination are used. And those have been treated for about 60 years now with what's called an anterior temporal lobectomy, which is where the hippocampus and a fair amount of adjacent tissue is removed.
And this has been quite successful. About 75 or 80% of these patients will have very few or no seizures. So the traditional surgery is a fairly large area of tissue. And there's been attempts over the years to take out smaller amounts of tissue, which is technically more difficult, but there's been long term attempts to develop tools that might give a more precise treatment with less resection of tissue and less side effects. One of those approaches has involved implanting neurons.
These cells that are produced by Neurona Therapeutics are cells that are able to be made into very specific cells. Now, there's the ability to take stem cells, differentiate them into specific cell types, and then to save them in very specific parameters so that they're always the same in every sample. For this treatment of epilepsy, the cells are differentiated into inhibitory cells, and those are cells that release GABA or gamma-aminobutyric acid. It's a neurotransmitter that's used by inhibitory neurons to signal other neurons.
The cells that produce it are primary what are called interneurons, and they usually involve modulation of the major cells, the excitatory cells, both input and output. It's felt that much of the, underlying cause of epilepsy has to do with inadequate inhibition or excess excitation.
Host Amber Smith: Well, let me ask you, when these implants arrive, before they're put into the patient, the cells are already part of the implant?
Robert Beach, MD, PhD: So the cells are a sample of a specific number of these differentiated inhibitory neurons in a liquid solution that are frozen into multiple different aliquots that are virtually identical. After they come here from the company in San Francisco, they are characterized, tested for viability and contaminants. And, then once that's all established, they're put into a cannula that is the delivery system.
The hippocampus is deep in the brain, and the best way to get to it without disturbing other tissues is using a long, tiny cannula that goes into it from the back of the brain. Once this cannula is in place, very tiny amounts of the cells are released at four or five different places and then are allowed to integrate with the patient cells.
Host Amber Smith: I'm envisioning this cannula like a tube. Is it like a skinny straw?
Robert Beach, MD, PhD: It's like a needle, much smaller than a straw, but it's the same principle, I guess.
Host Amber Smith: OK. So how soon after the implant is in place would patients notice a reduction in seizures?
Robert Beach, MD, PhD: Well, we don't really know. The initial hypothesis was that it would take integration to the cells, which could take months. However, we saw change in less than a month in both patients. So we think that it's not just integration, but possibly release of the inhibitory GABA even before the cells are directly interacting completely with other cells.
Host Amber Smith: This is Upstate's "The Informed Patient" podcast. I'm your host Amber Smith, and I'm talking with Dr. Robert Beach about an exciting new treatment for severe forms of epilepsy.
So other than the improvements with the reduced number of seizures, are you seeing other improvements in these patients?
Robert Beach, MD, PhD: Well, it's a bit early, but in our patient we did notice some improvement in some memory measures. And also we were able to lower his medications, which were at pretty high doses prior to the implant. And I think some of his benefit comes from just reduction of the side effects of the high dose seizure meds.
Host Amber Smith: That's encouraging. So what happens to the implant over time?
Robert Beach, MD, PhD: Well, we think it integrates, based on rodent studies. It can be demonstrated to persist for many months after implantation and appears to be stable. We assume that would be similar in the human, but we haven't really demonstrated that yet.
Host Amber Smith: Are there any negative side effects that you've become aware of?
Robert Beach, MD, PhD: I think the side effects that exist are related to the fact the patient has to be immune suppressed, and some of these immune suppressant drugs have side effects. And of course, they put the patient at increased risk for some infections -- which are generally carefully guarded against and has not happened in our patients -- but that's a risk.
Host Amber Smith: Well, I know it's still early, but does this seem to you like it's the dawn of a new era in epilepsy treatment?
Robert Beach, MD, PhD: Well, this is a very singular type of epilepsy, but it is one of the most common intractable types. And I think this will definitely develop into a treatment option that rivals the other ones and may be proved superior over time.
Host Amber Smith: As you were describing earlier, it's for a specific type of epilepsy that starts from a specific area of the brain, but now that it looks like it's beneficial for those patients, do you think it might be tried in patients that have epilepsy that starts in other areas of the brain?
Robert Beach, MD, PhD: I think so, as long as it's in a small area that can be very precisely identified, because we are only putting in a very small number of cells. To put in a large amount might cause some imbalance in the overall network. But there are other seizures that come from similar foci that can be fairly similarly characterized.
Host Amber Smith: Now the patients we're talking about are adults. Is that right?
Robert Beach, MD, PhD: Yes. This is only for adults so far.
Host Amber Smith: In the future, would it perhaps be looked at for children as well?
Robert Beach, MD, PhD: If it's successful it would definitely be looked at for children, yes.
Host Amber Smith: Now, could it be a strategy to treat milder forms of epilepsy?
Robert Beach, MD, PhD: Possibly, but the seizures that are most difficult to control are the ones that at least are most logical at this point.
Host Amber Smith: Can you think of any other neurological diseases that might be helped by regenerative cell therapy?
Robert Beach, MD, PhD: There's been trials of similar cell implants or different cell implants, I should say, in Parkinson's disease patients for more than 25 years. The success rate has not been as clear. The area where the cells need to be put for Parkinson's is perhaps a little less well-identified than the seizures. I think the more precise information on treating Parkinson's with similar cells may well turn out to be effective.
Host Amber Smith: That's good to know. Dr. Beach, thank you so much for making time to tell us about this.
Robert Beach, MD, PhD: Thank you for having me.
Host Amber Smith: My guest has been Dr. Robert Beach. He's a professor of neurology and chief of epilepsy at Upstate. "The Informed Patient" is a podcast covering health, science and medicine, brought to you by Upstate Medical University in Syracuse, New York, and produced by Jim Howe. Find our archive of previous episodes at upstate.edu/informed. This is your host, Amber Smith, thanking you for listening.