Combining Devices and Medication In the Future of Neurology Treatment


The CEO and Chairman of the Board of Directors at INSIGHTEC offered his perspective on how technologies such as focused ultrasound can help shape the future of neurologic care.

Dr Maurice Ferre

Maurice R. Ferre, MD, CEO and Chairman of the Board of Directors, INSIGHTEC

Maurice R. Ferre, MD

Focused ultrasound systems, such as INSIGHTEC’s Exablate system, among other technologies, have helped push the treatment of movement disorders forward and is poised to do so in a number of other disease states.

In a conversation with NeurologyLive, Maurice R. Ferré, MD, CEO and Chairman of the Board of Directors, INSIGHTEC, spoke about this potential, offering insight into how it might make an impact through additional uses, such as its ability at low frequencies to allow medications to cross the blood-brain barrier. He also offered his perspective on how these technologies can help shape the future of neurologic care.

NeurologyLive: Outside of the movement disorder space, are there any other disease states or uses being explored with this focused ultrasound system?

Maurice R. Ferré, MD: With the movement disorders—essential tremor, Parkinson, et cetera—we're kind of on the what we call the high frequency, or the lesioning, where we have enough energy for those thousand elements of ultrasound beams that are penetrating through the skull are corrected, and they all kind of go to a very simple target that steerable and we can get the temperature up to over 55 C's, which is which denatures the tissue and causes the lesions, where we can treat these types of diseases. What's really remarkable is that we can stage it. We can actually do it at a lower temperature and see if we get a signal. The patients, in terms of looking at their tremors, we can detect that in real-time, and then all of a sudden, we can tweak the delivery and move it appropriately to get the ultimate reaction. With this procedure it is immediate in terms of the outcomes, unlike using radiation therapy where you have to wait a few months to see the results of the lesion occur—this happens immediately. This all been in the heating side of it.

The other modality that we've been working on is what we call the low frequency. And what's interesting about the low-frequency modality is that when you put it in combination with microbubbles, and microbubbles that are normally used for cardiac imaging, where they have a very short half-life. When the ultrasound beam, at a low frequency, targets it, the microbubbles start to oscillate, and they enlarge, and they create sheer inertia and temporarily open up the blood-brain barrier through expanding the tight junctions. And this allows us to put agents into the brain that normally would not get into the brain. The blood-brain barrier is a protective mechanism to keep things out, and in most cases that something very important, but it's also limiting because you can't get a high concentration of certain types of drugs and 99% of small molecules that are used for all different types of treatments of this diseases never get into the brain. We have a technique that is noninvasive with a focal element, closed-loop system that's transient—that opens up the blood-brain barrier for about 12 hours, and then it goes back. Why is that important? Because now we can like look at different types of diseases like neuro-oncology, like glioblastomas, like brain METs, and be able to put a higher concentration of a drug in a targeted area without giving systemic load and allows us to have a bigger impact.

Now we're in these trials, and we're very early. We’re in phase 1 trials. But we're very encouraged with the direction that this technology is going. The potential that this could have down the road for treating these types of diseases, and not only on the neuro-oncology side. We can also start addressing some of these neurodegenerative diseases where there have been very few cures and there been a lot of failed trials because the concentration of the drugs that you're trying to put into the brain isn't high enough. We've been able to globally now treat in over 300 sessions, and we have now 5 different trials that are ongoing around this globally, and though it's early, I think it's going to have it has the potential of having a very large impact and giving another tool to the neuro-oncologist neurologist and the neurosurgeons in delivering a targeted therapy in the brain.

What should clinicians expect from the technological advancement in medicine in these next 10, 20, or 30, years?

What excites me about the future in neurology is that it's really kind of this multidisciplinary approach in trying to solve challenges that we've not been able to crack. Take, for example, glioblastoma. For 40 years, we've not changed the standard of care and it's a horrendous disease that has a very poor outcome, as we all know. There have been multiple attempts, and all of them have been kind of doom and gloom. Alzheimer seems to be kind of following the same type of path. We have this horrendous disease called the DIPG, diffuse intrinsic pontine glioma, that just has a horrendous outcome on children—and we've tried, there have been multiple attempts, and it's been a lot of work done and no outcomes.

What I think are opportunities and I think you’ll see companies like ours and others using different types of disciplines—in this case, physics and energy—to do something that's mechanical or targeting a mechanism in the brain, that's just not with drugs. The pharma companies don't understand the device world, and the device world doesn't understand the pharma world or the biologic world, and I think that we're going to see opportunities of combined therapies that will be targeted drug deliveries, that will use a combination of devices and drugs to be able to give a high dose of high concentration in a targeted gene expression type of approach. That's going to enable us to do something specifically in a very targeted area. Things like mechanisms like what we're doing and using energy—focal energy—using things with microbubbles and inertia and all these types of things are going to be really critical. I think a lot of this stuff is going to be noninvasive, incisionless. The fact that we're not using ionizing radiation to do this is meaningful because when you look at a lot of the studies of using radiation, they're these enormous adverse effects. Now, that's not to say that we don’t have to be diligent—there are no shortcuts here. We've got to go and get clinical data, we have to look at the risk, we have to understand things like edema, and ischemia, and things that can have adverse effects. We have to be very cautious.

That's why the way we use our technology, we use it inside an MRI machine because there we have the best controls and we're able to do a closed-loop system so that we can see right on the spot exactly when and where and how we control the opening of the brain or the lesioning of the brain. These are closed-loop systems, and I think that's going to be really critical the more and more we get into these things. I'm very excited about this opportunity of seeing these combined therapies, whether it's a compound, whether it's a gene, whether it's a cell that's being expressed, because we know that there's a lot of toxicity that goes in when we deliver these things systemically, and a lot of them in the brain is not very effective because it's not very targeted. That is going to be a huge value creator that I think it's going to have a huge impact on the way that we look at diseases.

Transcript edited for clarity.

Related Videos
Bruce Cree, MD
Christos Papadelis, PhD
Ro'ee Gilron, PhD
Monica Verduzco-Gutierrez, MD
Shahid Nimjee, MD, PhD
Peter J. McAllister, MD, FAAN
Video 6 - "Utilization of Neuroimaging in Alzheimer’s Disease"
Video 5 - "Contribution of Multiple Pathways to the Development of Alzheimer’s Disease"
© 2024 MJH Life Sciences

All rights reserved.