Focused Ultrasound - Treating Disease Without Surgery... Dr. Neil Kassell, Founder and Chair, Focused Ultrasound Foundation
Quick. What is being studied for a diverse range of conditions in numerous clinical trials around the world and actually approved for some treatments? It isn't a pill. It isn't an injection. It's been around for quite some time, and it's also readily available.
Dr. Moira Gunn:Doctor. Neal Kassell is the founder and chair of the Focused Ultrasound Foundation. He joins me to talk about what Focused Ultrasound is and the many ways in which it is being used today. Doctor Kissell, welcome back to the program.
Dr. Neal Kassell:It's a pleasure to be with you again, Moira.
Dr. Moira Gunn:Now the first thing I wanna say to listeners is that you may never have heard of focused ultrasound before, but it is being researched all over the world. There are nearly a thousand commercial treatment sites where you can get treatment all over the world. Hundreds of scientific papers are being produced and it's in use at major university research hospitals that you know of and, many companies in this space, numerous regulatory approvals, numerous clinical trials underway for a variety of potential applications. It may be new to you if it is new, but this is by no means new. Still, I was hoping, doctor Cassell, since there are those who have not heard of it, what is focused ultrasound, and what does it do when it comes into contact with the human body?
Dr. Neal Kassell:So focused ultrasound is an early stage, highly disruptive, revolutionary, totally non invasive therapeutic technology that holds the promise to transform a whole variety of serious medical disorders. And it's rapidly growing. Ten years ago there were only three medical disorders in various stages of research and development and commercialization. Today there are more than 180. So the way focused ultrasound works is analogous to using a magnifying glass to focus beams of light on a point and burn a hole in a leaf.
Dr. Neal Kassell:But with focused ultrasound, instead of an optical lens focusing beams of light on a point to burn a hole in a leaf, we use an acoustic lens to focus multiple beams of ultrasound energy on targets deep in the body with a high degree of precision and accuracy sparing the adjacent normal tissue. So where each of these individual beams goes through the tissue, it has absolutely no effect because it only has the power of diagnostic ultrasound. But at that focal point where the beams converge, we now understand more than 30 ways in which ultrasound can affect tissue. Ten years ago, we only understood five. And this includes destroying tissue by a variety of mechanisms, delivering drugs and other therapeutic agents in extremely high concentrations, higher concentrations that can be achieved by the normal routes of administration, which improves the efficacy and decreases the systemic toxicity.
Dr. Neal Kassell:It could be used to enhance cancer immunotherapy drugs and so on. The fact that there are so many different mechanisms of action is what creates the opportunity to treat this large number of serious medical disorders. In contrast to for instance radiation therapy, which only has one mechanism of action or a surgical robot, which only has one mechanism of action. And the point in the body where the ultrasound is focused is guided and controlled by medical imaging, either MR imaging or ultrasound imaging.
Dr. Moira Gunn:So if I understand this correctly, if there was just a single beam, not multiple beams, but a single beam, it would go through me. Nothing really would happen. But if you put them all together, focused at a very tiny point, then we see activity.
Dr. Neal Kassell:We see many ways in which it can affect tissue. It's a whole new way of delivering drugs and other therapeutic agents more safely and effectively. It's an amazing, amazing new technology.
Dr. Moira Gunn:Now I think everybody can understand how it could go down to the cellular level and destroy cells we don't want, but it's a little more difficult to understand how it could deliver drugs. How would that work?
Dr. Neal Kassell:Well there's a large number of ways in which focused ultrasound can be used to deliver drugs and other therapeutic agents. I'll give you an example in the most simple sense. You can use microbubbles, which are hollow lipid spheres, approximately a tenth of a diameter of a red blood cell. And these microbubbles can be loaded up with drugs, chemotherapy agents for cancer, genes or growth factors for Alzheimer's or Parkinson's disease, or ALS or Huntington's disease. And millions and millions of these microbubbles with the drug inside are injected intravenously and they circulate throughout the body.
Dr. Neal Kassell:Wherever the blood goes, the microbubbles go to every tissue and every organ. But the drug is totally inactive because it's trapped in the microbubble except at the point where the ultrasound is focused. And at that point, and that point only, the micro bubbles burst and release their pharmacological payload.
Dr. Moira Gunn:Well, when we think about taking, whether it's pills, IV drugs, any of this, we know they go all over our system. And in fact, that's where many of the side effects come because we have this drug in the entire system. But you're saying, well, we could send it to you. It'll go all over the system, but it's only going to burst. It only gets delivered where we direct the focused ultrasound.
Dr. Neal Kassell:Exactly.
Dr. Moira Gunn:Now, while this is worldwide and, there, there are many clinical trials that have happened successfully, many underway now. What conditions today have been approved in The United States for the focused ultrasound?
Dr. Neal Kassell:In The United States, there are nine clinical indications that have been approved. Around the world it's 31. And this includes prostate cancer, benign prostatic hypertrophy, essential tremor, Parkinson's tremor, Parkinson's disease, pain from bone metastasis, uterine fibroids, and so on.
Dr. Moira Gunn:I wanna give people a perspective, in the sense that anyone who is listening, grew up with X-ray machines. They were everywhere. In doctor's offices, you knew who would use them for what in hospitals. And, what we didn't know, we hadn't thought of is they weren't always there. You know, in the nineteen hundreds is when they first came into use, and it took a while for them to spread around and have adoption.
Dr. Moira Gunn:And this is what we're looking at today in a sense, in that focused ultrasound machines were coming out new, but we're in a different time. We don't just put them in someplace and say, well, let's see how this works. There are steps that have to be taken, regulatory steps. We have to make sure they work and that they're safe. It takes more time today for a technology like this to be moved forward.
Dr. Neal Kassell:It does. It takes it takes a long time. And today around the world, there are about a thousand commercial treatment sites. In 2022, about a hundred thousand patients were treated around the world for a variety of medical disorders using focused ultrasound in these 1,000 commercial treatment sites. It is our belief that in the next five to ten years, more than a million patients, well over a million patients will be treated every year in about 10,000 commercial treatment sites.
Dr. Neal Kassell:So these technologies evolve from an idea or a concept to a global standard of care, widespread utilization as a global standard of care, they evolve exponentially. And in the last couple of years, we finally passed the inflection point of this curve where the dialogue has clearly shifted from if focused ultrasound is going to have a major role in the therapeutic armamentarium to when, from if to when. But more importantly in the last twelve to eighteen months, the field is transitioning from what's been historically a research and development environment to a commercial patient treatment environment. And we're going to see, as I said, in five to ten years, more than a million patients treated each year. There's now 71 manufacturers of these focused ultrasound devices.
Dr. Neal Kassell:Ten years ago, there were only five. So the field is rapidly evolving, not rapidly enough to satisfy our needs, but rapidly evolving.
Dr. Moira Gunn:Now you're a long term professor of neurosurgery at the University of Virginia, and overlapping with that, you founded and shared the Focus Ultrasound Foundation almost twenty years ago now. When did this technology come to your attention? Tell us about that.
Dr. Neal Kassell:It's a little bit of a long and complicated story. So about twenty years ago, I was casting about for a solution to a relatively large number of patients I had with brain tumors in surgically inaccessible locations, or patients whose brain tumors had maxed out on surgery and radiation and chemotherapy, and there was no alternative. So I was looking for a non invasive or minimally invasive approach for this large number of patients. And serendipitously I was operating on a patient with an aneurysm in August about nineteen years ago and the anesthesiologist, it was a cardiac anesthesiologist, said, I've been doing studies measuring the blood flow in the heart muscle with microbubbles and ultrasound and watching the microbubbles wash out of the heart muscle. Why don't you try the same thing on the brain?
Dr. Neal Kassell:And we did, it was a good way of measuring blood flow in the brain experimentally. And then one Friday afternoon at 04:30, I can remember exactly the location and the time, I was driving home and the light bulb went off in my head and I said, I bet that we could use ultrasound plus or minus microbubbles to treat these otherwise untreatable brain tumors. And I got really excited because I'd been doing research since 1962 and I thought now, finally, I have a Nobel prize winning idea. I raced home, I went to the internet and discovered it was a Nobel prize winning idea, potentially, just wasn't mine, but that was okay.
Dr. Moira Gunn:Tough luck.
Dr. Neal Kassell:So that was my introduction. Yeah.
Dr. Moira Gunn:Well, it is amazing though. It's like those breakthroughs do lead you lead your mind to think of this one and then the one after and then the one after. You never know when they're gonna hit you. Today, there are sister foundations around the world, in Hong Kong, The UK, most recently in The EU, and where there are humans, you know, everywhere on the planet, there are the afflictions of life. I know there are many clinical trials going on today.
Dr. Moira Gunn:Can you just describe one or two that really pique your interest, that really push the push the envelope here?
Dr. Neal Kassell:Well, the two areas that we're most excited about are the brain indications, which include Alzheimer's and Parkinson's and ALS and Huntington's disease, OCD, depression, addiction, epilepsy, and so on, and cancer and cancer immunotherapy. So we're really excited particularly about Alzheimer's, the neurodegenerative diseases in particular, and enhancing or augmenting the effectiveness of cancer immunotherapy drugs because as we all know, these miraculous drugs are only effective in twenty to forty percent of patients, depending on the type of cancer. Focused ultrasound has the potential to increase that response rate to sixty, eighty, maybe even ninety percent. But there's early stage studies, there are clinical trials and all the indications are positive. The vectors are headed in the right direction.
Dr. Moira Gunn:Now, in the case of addiction, how might it be used to ameliorate addiction in some way?
Dr. Neal Kassell:Well, there's two ways. Number one is you can make small lesions in the brain, which will interrupt certain neural circuits. But more importantly, are using focused ultrasound to modulate neural activity, stimulate or block neural activity in certain regions of the brain, which is a way of controlling addiction for opioids, for food, and so on like and tobacco, alcohol, and so on. Again, these are early stage studies, but they're all very encouraging.
Dr. Moira Gunn:And now we turn to depression. I would assume that would be different.
Dr. Neal Kassell:So there are good clinical trials for OCD and depression where making very small lesions, very small areas of the brain will improve the lot of patients who are suffering with OCD or depression that have failed multiple drug therapies. In addition, there are other studies that are showing that you can treat OCD, depression and so on, and anxiety by neuromodulation without destroying any nerve tissue.
Dr. Moira Gunn:But what are you doing that's different from the way these people were before they What are you doing with the focused ultrasound?
Dr. Neal Kassell:Nobody knows 100% for sure, but when you think about it, one of the traditional treatments for these psychiatric disorders is electric shock therapy, which sort of resets the whole brain, okay? With focused ultrasound, instead of resetting the neural circuits for the entire brain, you're just resetting the circuits in specific areas of the brain that control craving for different substances.
Dr. Moira Gunn:So this is why it's called research. If we knew the answer, we wouldn't be doing research. And some of this is, you know, we really are out there at the edge of seeing what can be done with this technology.
Dr. Neal Kassell:Right, the purpose of research is to learn and that's what we're doing.
Dr. Moira Gunn:Well Doctor. Cassell, this has been terrific. Thank you so much for coming on and I hope you'll come back and see us again.
Dr. Neal Kassell:Look forward to it and thank you for the opportunity to share the story with so many of your listeners.
Dr. Moira Gunn:Doctor. Neal Kassell is the founder and chair of the Focused Ultrasound Foundation. More information is available at fusfoundation.org. The website contains a surprisingly long list of medical conditions, as well as the current state of research, development, and commercialization for each. This includes live clinical trials information and published research for over 100 identified medical conditions.
Dr. Moira Gunn:In addition, at this writing, nine medical treatments have been FDA approved, and an additional 35 medical conditions have received international approval. A full list of treatment centers, both domestically and globally, are identified for every medical condition using focused ultrasound for both approved treatments and current medical research. It lists such specific conditions as uterine fibroids and Parkinson's, prostate cancer and depression, glaucoma and hypertension. For example, in the case of essential tremor, as of 12/20/2022, the FDA has approved what is called stage bilateral treatment. In fact, the website clearly states that in The US, all treatment sites have been approved for payment under Medicare.
Dr. Moira Gunn:Again, for a full description of the experience of the treatment itself, the website for the Focused Ultrasound Foundation is fus foundation dot org.
