Dr. Kevin Lee, MD, neuroscientist and Professor of Neuroscience and Neurosurgery at the University of Virginia School of Medicine talks about an experimental non-invasive procedure that may someday treat movement disorders.
Interview conducted by Ivanhoe Broadcast News in May 2022.
What is happening when someone is epileptic?
DR LEE: Epilepsies are a diverse set of diseases – some of which are known how they occur, for instance, from an injury. You can have a head injury resulting in seizures. Some types of epilepsies, their origins are unknown. A very common disorder worldwide. There are 50 million people affected by this and approximately five million diagnosed annually.
For the five million and the 50 million who have epilepsy, are there drugs that work?
DR LEE: There are. There are anti-seizure medications; there have been since the 1800s, interestingly. And the efficacy of those drugs is fantastic. Even back in the 1800s, probably about 70 percent of the people that were treated with them were well-managed. Those drugs had severe side effects. In the last century, there have been several new anti-seizure drugs that have been developed that have the same level of effectiveness. That is, they’ll help about 70 percent of individuals, but have fewer side effects. So, great advances in the development of medical treatment of epilepsy over the last century.
Even with those advances, are there still patients for whom these things don’t work?
DR LEE: Approximately, a third of the individuals will not respond to medications. And they become good candidates for surgical removal of the area that is creating the seizures or generating the seizures.
When you say surgical removal, are you talking about open brain surgery?
DR LEE: Traditionally, there’s been open brain surgery, what’s called a resection that has been used to remove part of the brain that is responsible for generating the seizures. More recently, there have been great advances in the technology and the way to treat these seizures, including LIT – laser interstitial thermal therapy, and even more recently, noninvasive approaches such as high frequency ultrasound. There are advantages to both. High frequency ultrasound has the advantage that it can treat oddly shaped targets – oblong or something that’s not just a circle or a sphere. And that’s important because usually when you come in and try to look at an area that’s involved in generating seizures, it’s not something that’s perfectly spherical. So, you have to somehow coordinate the areas that you’re going to apply the focused ultrasound to.
What is PING?
DR LEE: PING is a procedure we came up with in the last five to six years. What we do with PING is introduce intravenously a drug that we know can kill those neurons. But it doesn’t get into the brain. So, it doesn’t get past something called the blood brain barrier. And the blood brain barrier excludes almost everything. It’s the bane of drug development for the central nervous system because this barrier is so efficient that it keeps 99 percent of drugs out of the brain. So, what we’ve done with PING is use a feature of focused ultrasound to open the blood brain barrier just in the target area that we’re interested in affecting and deliver this systemically administered drug only to the targeted region that is generating the seizures.
Is the PING not eliminating the difficult area but opening the barrier to allow the drugs in?
DR LEE: Precisely. It’s the difference between high frequency ultrasound, which will cause an ablation of all cells in the area – blood vessels, axons of passage, and so on. What’s different about PING is we’re going in with a much lighter, lower-intensity treatment that will only open the blood brain barrier allowing the delivery of the drug that we’ve administered intravenously. Why is it important to spare certain things and kill other things? An important feature of PING and a major advance of the procedure is that there are axons passing through areas that are generating seizures that you don’t want to damage. For instance, visual information can come into the brain and go through an area that’s causing problems. You’d like to knock out the area that is causing the problems, the real culprit cells, but spare the things passing through that are still functional. PING will do that, and the other procedures will not.
How does an MRI set up help with the delivery and the entire process of PING?
DR LEE: We use MRI for guidance purposes. When we want to identify our target in the brain, we can go in with MRI, scout out the region that we want to apply PING to, and then we can target that area selectively and even oddly shaped objects can be targets.
Can you explain what microbubbles are and how they are important?
DR LEE: Microbubbles are an important part of opening the blood brain barrier. Focus ultrasound on its own will not open the blood brain barrier, but when you introduce very tiny bubbles – one to two micrometers in size – when you put focus ultrasound into an area that has microbubbles, they cavitate and physically open the blood brain barrier. So, it’s not a chemical opening, it’s an opening that’s caused via those microbubbles resonating.
Are they safe?
DR LEE: They’re safe. They’re currently used for imaging and for contrast. We have great expertise here at the University of Virginia. I like to always highlight our colleagues. Sasha Klibanov is one of the leaders in producing those bubbles.
Can you tell me what you’re seeing notably from the testing with animals?
DR LEE: In addition to the ability to create damage that’s specific to the cell types that we want to target, we have looked functionally in an animal model of temporal lobe epilepsy. This is done with our colleagues at Stanford – Max Wintermark and Yanrong Zhang – and here at the University of Virginia with Ed Bertram, a neurologist. What we’ve done as a group is great fun; collaborating with people that are just totally into this. Even though they come from slightly different angles, we’re all committed to trying to find a way to treat epilepsy. So, in the animal model of focused ultrasound or in pain treatment of temporal lobe epilepsy, we’ve been able to demonstrate elimination or substantial reduction of seizures in animals that would have continued to seize for a long time. Eliminating seizures for patients is incredibly uplifting. Quality of life skyrockets. The ability to do day-to-day things without having to worry about a seizure coming on unexpectedly is a great thing. Being able to do that with PING in the future, hopefully, in the next five or 10 years, we’d be able to do it rather than bringing somebody into the hospital, having them stay for five, six, seven days to recover and then, having a severe scar following that on the scalp, we’d be able to bring them in and have what’s essentially an orthodontist visit. So, you come in the same day and leave the same day and are able to walk out with no or limited seizures. That’s the hope. Again, this is in the translational phase. These studies have been done only in rodent models, so far. There are things left to be done, but the progress that’s been made from resections to LIT, these minimally invasive approaches to frequency ultrasound. We believe that the next generation will be something along the lines of PING.
In what ways is PING like LIT and in what ways is it not?
DR LEE: It’s similar in its goals. What we’re trying to do with both of those procedures is reduce seizures, and a common goal to make epileptic patients have a greater quality of life. The difference between LIT and PING is that LIT is a minimally invasive procedure that will come in and destroy all cells in the region that it’s targeting. So, it will come in and produce a heat-based lesion of everything from the neurons that you want to target to the blood vessels, to the glial cells, things that are important for that, but particularly those axons that are passing through. I gave the example earlier about visual system information passing through an area that’s generating seizures. LIT will destroy those fibers, as well, while PING spares those axons that are passing through. So, it is more precise in terms of its cellular targeting. The other advantage of PING is that you can produce what’s called a conformal target, which means something that’s irregularly shaped, that you can form your target according to the shape that you want to hit. With LIT, you have just the end of a probe, essentially, coming into the brain and you can burn out a certain area. But if it’s oddly shaped, you may have to pull the probe out and come in from a different angle to eliminate the target entirely. So, PING would be more effective if developed and successfully in terms of providing a precise targeting.
What does PING stand for?
DR LEE: It’s Precise Intracerebral Neuronal Guided Surgery.
Is there anything else that you’d want to make sure our viewers know?
DR LEE: I think it’s important to understand that basic science contributes essentially to the clinical endeavors and that the National Institutes of Health are critical for bringing the next generations of treatments. We would never have been able to do any of this work without federal funding, and that federal funding is our lifeblood for getting these new technologies developed. So, absent that, there is no PING. And absent that, there is no next generation of treatment. So basic science, federally funded, contributing to clinical outcomes in the future is just essential.
END OF INTERVIEW
This information is intended for additional research purposes only. It is not to be used as a prescription or advice from Ivanhoe Broadcast News, Inc. or any medical professional interviewed. Ivanhoe Broadcast News, Inc. assumes no responsibility for the depth or accuracy of physician statements. Procedures or medicines apply to different people and medical factors; always consult your physician on medical matters.
If you would like more information, please contact:
Joshua Barney
1 (434) 906-8864
Jdb9a@hscmail.mcc.virginia.edu
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