Ep 64: Dr. Suzanne LeBlang – Focused Ultrasound Technology and Alzheimer’s Treatment (part 2)

Join us for part 2 of BrainStorm’s interview with Dr. Suzanne LeBlang, Director of Clinical Relations at Focused Ultrasound Foundation (www.fusfoundation.org). Host Meryl Comer and Dr. LeBlang discuss eligibility criteria and applications for the ground-breaking technology of focused ultrasound – a non-invasive procedure for treating tremors in Parkinson’s disease and those newly diagnosed with Alzheimer’s disease. This technological advancement can target and treat tissue deep within the brain, enhance drug delivery, and facilitate the removal of amyloid plaques. As featured on CBS 60 Minutes, patients are awake during this transformational procedure.  You won’t want to miss part 2 of this interview! 

Transcript

Dr. Susie LeBlang (00:00):

This was really a landmark trial. It was the first time a drug was combined with the blood-brain barrier opening in patients with Alzheimer's disease. You give Aducanumab, some of it crosses the blood-brain barrier. Some of it helps to dissolve some of that amyloid clearly in the frontal lobe of the brain that received the focused ultrasound therapy Compared to the side of the brain that didn't receive the focused ultrasound therapy, the amount of amyloid decrease in the focused ultrasound treated side was markedly decreased compared to the side that didn't receive the focused ultrasound.

Opening (00:34):

Welcome to Brainstorm By UsAgainstAlzheimer's, a patient-centered nonprofit organization. Your host, Meryl Comer, is a co-founder, 24 year caregiver and Emmy Award-winning journalist, and the author of the New York Times Bestseller, Slow Dancing With a Stranger.

Meryl Comer (00:52):

This is Brainstorm and I Meryll Comer, our guest, Dr. Susie LeBlang, a neuroradiologist and director of Clinical relations for the focused Ultrasound Foundation in part two, because there's nothing more disappointing than to raise your hand for a study or clinical trial and get rejected. I asked Dr. LeBlang to share the most common inclusion exclusion criteria for these non-invasive clinical trials.

Dr. Susie LeBlang (01:20):

So it's actually quite a lengthy list of inclusion and exclusion criteria, and I can direct everyone to the Fuss Foundation website, and you can go on clinical trials and look for Alzheimer's disease and actually click onto that site to look at it. But I would say some main things are the MMSE scores are tending to be between 16 and 24 right now. And if you're a POE four, which is a genetically predisposed type of Alzheimer's disease, you're tending to be excluded from some of these trials because we feel that these patients may be more susceptible to arias. Those are some changes in the brain that can cause some clinical sequelae. So right now in these early phase studies, we're really trying to be careful and pick really the perfect candidates to make sure we know how to do this, how to do it safely, and see what our effects are to navigate the next series of clinical trials properly.

Meryl Comer (02:10):

Dr. LeBlang, I've looked over the clinical trials your foundation supports in West Virginia. You're opening up the blood-brain barrier with Aducanumab patients with early cognitive disabilities. Are you working directly with the companies in the trial design? Tell us how that works.

Dr. Susie LeBlang (02:28):

So West Virginia University is using an insight tech machine in designing that clinical trial and doing it. And this was really a landmark trial. It was the first time a drug was combined with the blood-brain barrier opening in patients with Alzheimer's disease. So in that recent New England Journal of Medicine article highlighted also in the 60 minutes segment, as a radiologist, a picture is worth a thousand words. And let me try to create this picture for you. You give aducanumab, right? You give a drug. Some of it crosses the blood brain barrier. Some of it helps to dissolve some of that amyloid clearly in the frontal lobe of the brain that received the focused ultrasound therapy compared to the side of the brain that didn't receive the focused ultrasound therapy. But remember, in theory, every part of the brain got the aducanumab. The amount of amyloid decrease in the focused ultrasound treated side was markedly decreased compared to the side that didn't receive the focused ultrasound. So the thought, and what we've proven in ample, preclinical, and even clinical trials is that when you open that blood-brain barrier, you are getting more drug in. And if you are getting more drug in, more drug can help release that amyloid from that area. But if you take a look at that article and you look at the picture, you do not need to be a neuroradiologist to see the difference in the amount of decrease of amyloid in the fust treated side compared to the non fust treated side.

Meryl Comer (03:47):

The term neuromodulation is also used. How does it differ from opening the blood brain barrier?

Dr. Susie LeBlang (03:55):

So the focused ultrasound beam, like I mentioned before, you can kind of turn it to multiple dials to do different things. Almost like a light switch is not just on or off. Now you can have a dimmer switch of different levels of light, and the same thing with the ultrasound machine. You can have low intensity focused ultrasound, which is what we're doing with blood-brain barrier opening. High intensity focused ultrasound is with things like thermal ablation for essential tremor or Parkinson's disease where we raise the temperature to actually ablate attract in the brain. So within the low intensity focused ultrasound, you can open the blood-brain barrier. If you turn the energy down a little bit more, you can even do something called neuro neuromodulation. So with neuromodulation, you don't need any microbubbles or anything. But basically you can either take neurons that are not firing enough and they can fire more.

Dr. Susie LeBlang (04:40):

You can take neurons that are firing too much like an epilepsy and make them fire less. What they've shown in preclinical studies as well, and even in some clinical trials, is that with neuromodulation alone in patients with Alzheimer's disease, you are causing some physiologic changes that improve cognition. So you're changing the synaptic alterations. You're changing the extracellular matrix where some of that amyloid is so that it can maybe loosen up a little bit and get digested. You're changing the NMDA receptor. So the drug memantine is currently being used to treat Alzheimer's disease. So you're kind of doing something like that without the drug, and you're changing some of the electrophysiologic signaling that helps with Alzheimer's disease. So this is like another mechanism of action that's being employed to treat Alzheimer's disease. We have a separate amount of clinical trials that are just using neuromodulation for Alzheimer's disease.

Dr. Susie LeBlang (05:31):

So to just sum up the mechanisms of action, we can do neuromodulation to try to alter patients with Alzheimer's disease. We can do blood-brain barrier opening alone, where we know we're activating the microglia and we're also engaging the glymphatic system, which is a way to dispose of waste in the brain. So we're getting that amyloid to loosen up, and then it gets excreted through the glymphatic system. And then you've got the focused ultrasound blood brain barrier opening for drug delivery. So we think there's really three ways that you can use this focused ultrasound beam, and it's going to be like a aging, all of this. And understanding the physiology in each individual patient to know which mechanism of action or combination is best for that patient.

Meryl Comer (06:11):

What do you say to those who know their high risk because it runs in their family?

Dr. Susie LeBlang (06:17):

You know, that's a great, great question. And we get calls all the time from patients that are so willing to do anything and educate them about what the trials can do or can't do. We can't over promise right now, right? These are clinical trials for safety and now for efficacy. So if patients with advanced risk or advanced disease want to participate in clinical trials, we encourage them to go to the clinical coordinators for that sites and start to have interviews with them and talk to them about whether they would like to pursue the potential of engaging in a clinical trial for the benefit of research without a guarantee that we can improve them right now. But that's scientific research, and we appreciate every patient that offers to go into a clinical trial because it is a big sacrifice, right? Of time and risk. But you know, that's how science progresses. So we very much appreciate inquisitive patients, and I love patients that ask a lot of questions because they're more educated and then they understand what this entails.

Meryl Comer (07:15):

Having lived inside the disease with both my husband and my mother, I think it changes you forever about what you're willing to personally risk to advance the science. What do you see on the horizon when it comes to focused ultrasound and how it will change patient care and disease management?

Dr. Susie LeBlang (07:34):

Well, thank you for sharing that about your family, and I'm thinking of not only from the patient perspective, that even small amounts of clinical improvement make a huge impact in their quality of life, and how the caregiver, the needs of caregivers right now to take care of our aging population and the numbers of patients, like you said, with Alzheimer's disease and other dementias, is really overwhelming generations of friends and family members and the cost of caring for them. So this has huge societal implications. If we can create a incisionless therapy that can be done with patients awake with decreased expense, widespread availability, changing the course of lives for not only the patients, but caregivers and families is tremendous and so important with our aging population. So I'm working with the focused ultrasound foundation because I truly believe we can make a difference, not only for Alzheimer's disease, but for all the other neurodegenerative disorders.

Dr. Susie LeBlang (08:33):

We're doing research, ample research with Parkinson's disease, Parkinson's disease, dementia, as well as the movement disorders. We've been in clinical trials with blood-brain barrier opening for drug delivery with a LS Huntington's disease. We hope to start soon. So we're in this space because we feel we have a platform technology where we can open the blood-brain barrier, and opening that blood-brain barrier or doing neuromodulation could make that difference that in the last 20 years, the research has shown that the blood-brain barrier is such an impediment to getting important therapeutics into the brain. I think we're onto something, and I'm very proud to work with the West Foundation to help explore all of these options.

Meryl Comer (09:09):

Dr. LeBlang, whether it's the heart, brain, or gut brain connection, there is a growing awareness that all bodily functions are in fact controlled by the brain. What does that forecast in terms of the potential uses of ultrasound?

Dr. Susie LeBlang (09:25):

When you talk about all these things that we can do for neurodegenerative disorders or addiction, and regulating the sympathetic and parasympathetic nervous system and getting nerves to kind of fire and sync when they're not, or in a more controlled fashion, what we understand in the brain is increasing every day, but we still have a lot to learn. But I do think the ability of us to interrogate the brain non-invasively with this technology is going to teach us even more. We talk about the future with Alzheimer's disease, not only adding a drug like Lecambe or Aduhhelm, right? But there are other things. Anti-tau antibodies are coming on GSK three inhibitors, which prevent the amyloid from forming. And the holy grail would really be a gene therapy, right? A one and done. Can we get a gene therapy to go to certain cells in the brain that will really help regulate and decrease the formation of amyloid or tau deposits? You know, gene therapy is a really holy grail for us with targeted drug delivery and the blood-brain barrier opening. So I want them to just make sure that people know that we are working on that. We have a very big program at the foundation to help with gene therapy delivery.

Meryl Comer (10:24):

Dr. LeBlang, with all the positive excitement around the use of evolving technologies, there is always the concern about a dark side and misuse of technologies. What are your ethical concerns?

Dr. Susie LeBlang (10:37):

Yeah, it's a double-edged sword. So we know of, you know, over a hundred companies in the focused ultrasound space from head to toe, right? There's probably 10 or 20 in the brain space right now, right? So on one hand, we want to make it so easy that it can be done in a doctor's office or even at home with feedback loops that let's say someone with epilepsy, if they see that if the sensors pick up the patient's about to have a seizure, they can do neuromodulation right away with a feedback loop and someone with Alzheimer's disease, can we put a helmet on them at home so they can do this treatment at home? Right? We want to make it accessible to people, but we also have to safeguard that if people are using a technology like this at home, they do it safely and effectively and don't abuse it.

Dr. Susie LeBlang (11:17):

So I think what scares me is that the fact that this is an incisionless, non-invasive technology is amazing, but could it possibly be used wrong if we're making it that easy to use? Absolutely. So I think the companies need to really work with the physicians and the patients to make sure everybody understands the power that's in here looks easy, but it can do a lot of things inside that brain, and we have to make sure we use the technology appropriately in the proper clinical situation, in the proper form. So I think that's something that has to be really measured and weighed.

Meryl Comer (11:51):

Thank you for sharing your enthusiasm for such a fascinating field and the work that you're doing. 

Dr. Susie LeBlang (11:55):

Thank you so much for having me, and thank you for your questions. 

Meryl Comer (11:59):

Our guest has been Dr. Susie LeBlang neuroradiologist and Director of Clinical Relations for The Focused Ultrasound Foundation. That's it for this edition. I'm Meryl Comer. Thank you for brainstorming with us. 

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Closing (12:50):

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