Ep 57: Dr. Rudy Tanzi - How to SHIELD the Brain (part 2)

Join us for part 2 of BrainStorm’s interview with Dr. Rudy Tanzi, Director of Genetics and Aging Research Unit and The McCance Center for Brain Health. Host Meryl Comer delves into whether Dr. Tanzi practices what he preaches on brain health and the efficacy of different brain health supplements to increase cognitive longevity. Dr. Tanzi, the Kennedy Professor of Neurology at Harvard Medical School, also spoke about the role AI plays in accelerating clinical trials and how his musical talents improve his creativity as a scientist. You won’t want to miss it. 

Transcript

Rudy Tanzi (00:01):

When I wrote “Super Brain” with Deepak, the message was, use your brain. Don't let your brain use you. Don't identify with your feelings and thoughts and suffer from anxiety or stress. Take that mountaintop view. Ask, what is your brain doing for you? Not what you're doing for your brain. Yes, brain care is how you take care of your brain, but the output of the brain, the mind is your tool. And a mistake we make is to identify too much with our emotions, feelings rather than observe them and say, what's my brain trying to tell me? And how can I change my life accordingly?

Introduction (00:32):

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 (00:50):

This is BrainStorm. And I'm Meryl Comer. Our guest, Dr. Rudy Tanzi, Director of the Genetics and Aging Research Unit and Director of the McCann Center for Brain Health at Mass General Hospital. He is also the Kennedy Professor of Neurology at Harvard Medical School. In part two of our conversation, he speaks to the value of AI accelerating clinical trials and reviews, some of the most popular brain health supplements. I asked him about the current state of Alzheimer's therapeutics and advancement in both invasive and non-invasive technologies.

Rudy Tanzi (01:26):

Neuro technologies are interesting where you can actually try to reduce age-related pathology relative to Alzheimer's with non-invasive electronic methods. Broadly electronic. There's some evidence that if you can entrain the brain to a gamma frequency, which is 40 hertz, and most of the time we're not in gamma. So right now as we speak, we're in alpha and beta. If you meditate when we're done, you're going to go down to theta. If you go to sleep, you go down to delta, you get slower and slower. Gamma is going up. We're right now at maybe 20 hertz. Gamma is 40 hertz. Well, it turns out that when you turn on certain neurons, nerve cells in the brain to fire 40 hertz, they can trigger those little scrubby bubble cells, the microglia to eat the amyloid. And we can see that in mouse studies. And there are clinical trials going on there.

Rudy Tanzi (02:14):

So you can entrain the brain with light flashing. You can entrain the brain with audio signals. A long time ago, we invented these glasses I'll show you here, which shine light from the back and the light flashing and trains the brain. So if you see those little white squares, they'll be flashing at 40 hertz slowly bringing you from your current 20 hertz up to 40 hertz, and using light to entrain the brain to 40 hertz to try to get those scrubby bubble cells going to the ware. So these types of trials are going on now. I think that's the most exciting in terms of neuro technologies. There's also some studies looking at wavelengths of light that an near infrared level, that if they can have certain devices like helmets to get that infrared light to infiltrate the brain a bit, that can also be a way to induce the removal of the amyloid. And I should mention that these same little cells that eat the amyloid when they're housekeeping are the cells that cause inflammation when they're killing. They're truly a Dr. Jekyll and Mr. Hyde. So a lot of what we're doing with our drug discovery now, or neuro technologies, is trying to get these microglial cells as they're called to go from being killers, which causes inflammation back to being housekeepers where they clear amyloid at night while you sleep or when they're encouraged by a good diet.

Meryl Comer (03:22):

Rudy, earlier you mentioned accelerating clinical trials by repurposing approved drugs that are safe or natural products. What excites you the most in this space right now?

Rudy Tanzi (03:34):

Well, the first big excitement came 10 years ago when our lab invented Alzheimer's in a dish. So we developed a mini human brain organoid in which we could induce amyloid, and then the amyloid induces the tangles, and then it would bring in the inflammation. So in this mini human brain organoid in a Petri dish, we could recreate what takes 30 years in the brain from amyloid to tangos to inflammation. 30 years in six weeks, 30 years down to six weeks in a mini lentil sized brain organoid. That discovery at the time, if you remember that got me on the time 100 list because they said this is going to make drug discovery 10 times faster and 10 times cheaper than having to test one drug at a time and a mouse for a whole year. We could have a plate with a hundred wells in it, each one with a lentil size mini brain, and test a hundred drugs at a time.

Rudy Tanzi (04:25):

It's actually made drug testing a hundred times faster and probably a hundred times cheaper. So we've spent, with the help of the Cure Alzheimer's Fund over the last seven years and about $5 million of funding from the Cure Alzheimer's Fund, we screened every known approved drug that's already safe and thousands of natural products, many of which you could buy as supplements. And we said, which ones work? Which ones blow up the match? Get rid of the amyloid, which ones don't let the match stop the brush, fire, the tangles? And most importantly, which ones put out that virus fire, the neuroinflammation, the inflammation in the brain. And we've come up with hundreds of hits, hundreds of approved drugs and natural products that do this. And I take 10 or 11 of those natural products every morning myself. We don't have clinical evidence, but these are deemed to be safe. I started a new company last year called ACTA Pharmaceuticals where we're doing actual combinations of natural products and saying, let's get the data. Let's not just have people say, trust me, my brain pill works. There's a lot of snake oil out there. You know that, right? Let's generate clinical data using natural products, have already worked on Alzheimer's pathology in a mini human brain organoid in a dish. That's the next step.

Meryl Comer (05:33):

Rudy, there's no question that there's angst about brain health. And in fact, I just looked up the brain health supplement market and it's projected to reach 17.4 billion by 2028, and

Rudy Tanzi (05:45):

90% of those products do nothing. The usual problem is it's a capsule this big and they brag 15 different ingredients. Well guess what? Smattering of each one. There's not enough of any one of them to make a difference. Be careful when you see somebody bragging about how many ingredients are in their pill. because if the pill's that big, there's not enough of any single ingredient to make a difference in your brain, even if they're putting in the right stuff. Then you got other ones that are just making broad claims that this is going to help your brain. I won't mention names where there's no evidence whatsoever. Then they say things like, clinically tested. Well, yeah, what was the result? Oh no, it was clinically tested. Oh yeah, they work. No, no, it was clinically tested. So I mean, come on. So there's a lot of bunk out there, a lot of snake oil.

Meryl Comer (06:24):

Rudy, let's run through a couple of the popular supplements promoted as targeted to improving brain health. Let's start with turmeric.

Rudy Tanzi (06:32):

Well, turmeric is anti-inflammatory, but the main ingredient in turmeric, curcumin doesn't get into the brain. So there are people who sell versions of curcumin that are meant to get into the brain because they're in particles. I'm not personally convinced we have a product that gets the curcumin into the brain as much as I'd like to get curcumin into the brain.

Meryl Comer (06:49):

Next, a recent news headline that read is The Fountain of Youth really filled with Red Bull. One of the ingredients is trine.

Rudy Tanzi (06:58):

Trine has legs. I'm not saying go drink Red Bull, it's full of caffeine too, but you know nothing against it before it. There's increasing evidence that trine levels go down with age. And in fact, one of the companies I helped start called Alyx repurposed a toine type chemical called T-U-D-C-A, TUDCA Toridol, together with another known drug called Phenyl butyrate combined those and then we tested those, the A LS. Now for disclosure, I have founding shares and Aly, which is now a public company, and that combination of two approved drugs are now on the market as an A LS drug called Rio, and ranked to be actually more effective than the existing a LS drugs based on the original clinical trial data. It's the only combination that not only promotes survival in a LS patients Lou Gehrig's disease, but helps symptoms. And now that same combination is being used in Alzheimer trials by the same company amyx. So one of the ingredients of that successful combination is a trine type analog called Tudca, T-U-D-C-A. So yeah, I think Trine deserves much, much more investigation. And we're actually investigating it in my lab too.

Meryl Comer (08:01):

How about metformin?

Rudy Tanzi (08:03):

When we did our drug screen where we screened every drug known in our Alzheimer's in a dish model, Metformin, you know, was one of the hits. It wasn't one of the best hits, it wasn't one of the worst, it was a middle of the road kind of average hit. But what's interesting about Metformin is that it helped reduce the tangle formation in response to the amyloid and it had some effect on the inflammation. Now, whether metformin is strong enough in current doses to see in a human, what we saw in Alzheimer's pathology in the dish, I'm not yet convinced of, but we'll know soon because there are trials going on with Metformin and Alzheimer's that should read out at some point, and we'll probably have a clinical indicator of that pretty soon.

Meryl Comer (08:38):

Because all of these brain supplements are pricey. There's a new one out with celebrity endorsements that has come under fire Riva Plus,

Rudy Tanzi (08:46):

My view on Riva is that it has a lot of natural products in it that I agree are good, many of which did well in our Alzheimer's in a dish. But I worry that you have so many of them. In one little pill, there is something called dose dependence. And even in our dish model, you know, when we see certain natural products work, you have to have enough of them to work. So I worry about not picking on Riva, but I'm picking on any brain pill that has 10 or 15 ingredients and there's not enough of any one of them to hit the right dose to make a difference. I've never tested it, but I do worry about that class of supplements.

Meryl Comer (09:20):

Rudy, one last question in this space, what's your view about certain cholesterol medications and their potential to help prevent dementia?

Rudy Tanzi (09:28):

There have been data now for decades that say statins are associated with protection against Alzheimer's. And one thought is if you keep your cholesterol in check, just like on a brain cancer score, we ask about cholesterol, high cholesterol leads to vascular effects, could lead to stroke. Many strokes can cause the pathology that leads to Alzheimer's. It's not surprising that what's good for the heart is good for the brain. And I think there are enough epidemiology studies. Some say yes, it protects, some say no, some say maybe. But I think the meta-analyses I've seen suggest that overall statin as a managing cholesterol is good for the brain and does help reduce age-related brain pathology, which happens to be mostly Alzheimer's pathology.

Meryl Comer (10:08):

Rudy, tell me, where does your research on brain health intersect with the billions being spent in the quest for longevity? I mean, tell me what good is lifespan without brains span?

Rudy Tanzi (10:20):

Well, you said it. What good is lifespan without brains span? Our lifespan thanks to modern medicine has far outpaced our health span. It's especially true in the case of the brain. Our brain health span is way behind lifespan. So I go to meetings where folks just care about how long they're going to live. And I'm like, well, fine, but don't you want a brain? Don't you want to know your living? So I mean, come on. We have to emphasize health span over lifespan, and we have to specifically emphasize brain health span because right now brain care doesn't exist. We're trying to make brain care exist with the Brain Care score. We're trying to get people to use shield, we're trying to get people to take care of their brains. I wrote The Healing Self with Deepak Chopra. That's where SHIELD came from, was from our action plan in that book about how to reduce inflammation in the body and brain. So we need to be our own doctors. Go to a doctor when you need one, but don't wait to take care of yourself before you see a doctor. You can take care of your body and brain in a very effective manner every day following shield.

Meryl Comer (11:14):

You mentioned earlier that you're in the midst of writing another book. Well, you've already co-authored Decoding Darkness, super Brain, super Genes, and the Healing Self. Rudy, every time you write a book, is there a personal takeaway that somehow changes how you live your life?

Rudy Tanzi (11:32):

Well, you know, they say that what you write about is what you most need yourself. When I wrote Super Brain with Deepak, your message was, use your brain. Don't let your brain use you. Don't identify with your feelings and thoughts and suffer from anxiety or stress. Take that mountaintop view. Ask, what is your brain doing for you? Not what you're doing for your brain. Yes, brain care is how you take care of your, your brain, but the output of the brain, the mind is your tool. And the mistake we make is to identify too much with our emotions, feelings rather than observe them and say, what's my brain trying to tell me? And how can I change my life accordingly? That was super brain. Well, there's a reason why I wrote that book. I needed that advice myself. The best books are when somebody who writes it really needed that help themselves.

Meryl Comer (12:12):

Rudy, there's great debate about how to deploy artificial intelligence. What are its potential applications in accelerating dementia research or even early diagnosis?

Rudy Tanzi (12:23):

Artificial intelligence AI is used all the time now. In our research, we're trying to analyze reams of data from your metabolites to your lipids and fats, to your gene activity, to the array of proteins you have in your blood. The inputs of data. Now, thanks to omics lipidomics genomics, transcriptomics metabolomics is terabytes of data. It has exceeded the ability for me to sit down looking at an Excel sheet saying, aha, the eureka moments are going to have to come from the computer now because it's just too much data to metabolize with just a hundred billion neurons and a few trillion synopsis in your brain. So I'm happy to use ai. AI is helping with diagnoses, it's helping with treating diseases, it's helping with interpreting research data. It's here to stay. It's a wonderful tool. You now do I worry about AI and the matrix and are we going to someday be serving the machines and AI we've created? Well, sure we all have to worry about that as well. But right now it's just a wonderful tool that I think is advancing research and medicine exponentially ever more than before.

Meryl Comer (13:23):

So why not create a virtual version of the Framingham heart study that has really tracked families longitudinally to collect and analyze indicators of brain health?

Rudy Tanzi (13:34):

Well, remember that the Framingham study already had the indicators of heart health available to collect before. You can do the same for the brain. You have to have the indicators of brain health. Health. We started the McCann Center for Brain Health to develop and discover those indicators. And we don't have a stethoscope or a blood pressure cuff for the brain, but we're now, we're getting there. Now. We have proteins we can measure in the blood to tell you whether you're developing amyloid or tangles or neuroinflammation. That's not a company called React Neuro disclosure, I'm a founder with equity that uses a virtual reality device with eye scanning and voice analysis. So you're doing a neuropsych exam in virtual reality. It's checking the movement of your eyes, which is indicative of your brain health, how smoothly or faster eyes can move. It's assessing your language assembly and your voice cadence.

Rudy Tanzi (14:25):

And it has an algorithm that then puts all that together to tell you your brain health index. And this is being used now with sports teams. It's being used to track athletes. It's being used in senior living, so that's a digital technology. So it's happening digital technologies, ai, biomarkers in the blood. We now have the indicators of brain health that we didn't have five years ago. Now you can start collecting those data on large groups of people longitudinally. And now because you have the indicators of brain health, you can do a Framingham study on the brain like they did on the heart. And there are groups who are actually initiating studies like that right now around the world.

Meryl Comer (15:00):

So Rudy, there's an evolving area of science called Neuroaesthetics that examines the impact of music and the arts on the brain. Now you've played keyboard since you were a kid and now you've teamed up with Aerosmith and Joe Perry to even produce several albums.

Rudy Tanzi (15:17):

Three albums now. Yeah, one with Aerosmith and two with Joe Perry. The last one just came out in May of 2023. So yeah, I mean, I still do music and I got my studio set up behind me and I have my own website with my own music. My own music is very different than Aerosmith and Joe Perry. My own music is more jazz improvisational pieces, more along the lines of Keith Jarrett or Bill Evans. And I have a website called Nonem.com/Rudy Tanzi that has all my original pieces on it. And amazingly enough, more people hear my music than read my scientific papers because my website, I get about 30,000 listens on streams per day all free. Of course, I don't do it for money. So it's kind of cool. It's kind of cool to be able to get the music out there, but it was you who introduced me to Joe Perry Meryl. So this is all your fault. I'm

Meryl Comer (16:01):

Thrilled. I'm thrilled. In what ways has your musical creativity spilled over to influence your approach to science?

Rudy Tanzi (16:12):

Yeah, two ways. First of all, just being creative. I play every day and the pieces I write from my own website are extemporaneous and improvised along the lines of what Keith Jar approach of jazz. And I think the creative process in one area always spills over to another area. So just that creative process of music. Then if I go to my computer and I'm looking at data, you're in that creative mindset. So that's number one. Number two is the first conversation I had with Joe Perry back in 2009 when you introduced us in New York at the studio where we're doing the rock stars of science photo shoot. And that day way Joe Perry and I bonded was we were talking about how the best science is non derivative. It's being bold enough to do something new, channeling creativity rather than just rehashing what's already out there. Like I like to say, we emphasize in my lab the search and research, not the reit. And Joe Perry was saying, you know, for how he plays guitar and approaches his solos is the same way as to just never try to do cliche known riffs or licks. Always try to do something new, always be creative and do something new rather than derivative. And I think that's the difference between science that becomes great and music that becomes great versus just a rehash.

Meryl Comer (17:24):

So what's on your playlist for 2024

Rudy Tanzi (17:28):

<laugh>? My playlist in the lab is I'm very excited because a drug I've been developing for 25 years that will be a small, just a pill that will lower your amyloid levels, hopefully much more safely than the existing approved drugs and immensely more affordable since it's just a pill rather than an IV injection. It requires MRIs to make sure your brain isn't swelling or hemorrhaging. Our little pill will be just something you take like the way you take a statin like Lipitor for cholesterol. And it took 25 years to get to this drug. It's called the Gamma Secretase modulator or GSM. And I'm very excited because there's a chance that our first clinical trial for safety to see if it works, it's going to start this spring after 25 years of development and lots of money from the NIH and Cure Alzheimer's Fund to do this.

Rudy Tanzi (18:13):

This drug has the chance to be a godsend for those unfortunate individuals who inherit the early onset familial Alzheimer gene mutations For people who have those mutations in the early onset familial genes, they have a death sentence. Shield doesn't help them. They have mutations that guarantee the disease by 40, 50, even 30 or 20 years old, certainly by 60, it's only one or 2% of Alzheimer's, but it's the most devastating. Our drug was developed based on reversing what those mutations do. That's how we developed the drug. We did screens that say, let's just reverse what those mutations and those early onset familial genes do. And it took this long. Not only will this drug hopefully be useful for lowering amyloid and everybody who finds out by a blood test that they are on their way to amyloid or have amyloid in their brain decades before symptoms of Alzheimer's.

Rudy Tanzi (19:07):

But for people who have these mutations, they start taking this drug early in life. And the hope is it reverses the mutations. It reverses what the mutations do, and you give them a new lease on life. I always remember sitting in my office with a woman who was 30 years old and she had one of these mutations. She just found out she had the early onset familial mutation and her dad had died with Alzheimer's by 45 and her dad's sister by 47 with this mutation, I'm guaranteed to get Alzheimer's sometime in my late thirties or early forties. I said, yeah. And she looked at me and she said, so you're telling me that my two kids, when they're in college, I may not know their names like I feel now when I say it, it hit me like a ton of bricks. And I met one of my colleague, Steve Wagner, who's passed away now.

Rudy Tanzi (19:45):

He passed away last year of heart disease. He was a gentle guy from Louisville. And in his Louisville accent, he said, man, Rudy, we got to help her. I said, yeah. And we're like, let's just do a drug screen that reverses what her mutation does and maybe it'll be helpful for all of Alzheimer's. And that's what this drug hopefully is going to be. Took 25 years of development, about $40 million, we're ready for clinical trials. So I had to start a company to do that. I started a company I mentioned earlier, active pharmaceuticals is also besides repurposing approved drugs and natural products for trials who are developing this drug as the second major effort and hopefully getting our trials going this year. But if it works, that drug works and it's safe. It's going to be the one, it's just you get your blood test, you find out if you're in trouble, just like high cholesterol, you find out if your amyloid is ramping up, you take this drug and knock it back down and just wipe the state clean. Nip the disease in the bud. That's my hope. That's on my playlist for 2024. So more important than any music I'm going to listen to.

Meryl Comer (20:39):

Just remarkable, when will it be ready for the baby boom generation.

Rudy Tanzi (20:43):

So we're still talking several years out, but that's why in parallel, we're doing the known drugs and natural products. Because maybe we can get evidence there of things that work in the meantime until these new drugs, new chemical entities come to the fore. So we're doing these things in

Meryl Comer (20:56):

Parallel. So your advice to us is get our brain care score, improve our brain health today to reduce the risk for brain disease in the future. Right?

Rudy Tanzi (21:06):

Practice brain care to preserve and promote your brain health and reduce your risk for brain disease later. And it starts with shield and it starts with following the brain care score.

Meryl Comer (21:15):

Thank you, Rudy. We always look forward to our annual check-in our guest has been Dr. Rudy Tanzi, director of the Genetics and Aging Research Unit, as well as Director of the McCann Center for Brain Health and Mass General Hospital and Professor of Neurology at Harvard Medical School. That's it for this edition. I'm Meryl Comer. Thank you for brainstorming with us. Our team is on a mission to help you stay up with the latest scientific breakthroughs from new therapies to technologies on early diagnosis and personal brain health advice from well-known experts using an equity lens that promotes brain health for all. Now we'd like to hear what's on your mind, what are the topics and guests you'd like to hear featured on? Brainstorm? Send your comments to BrainStorm@UsAgainstAlzheimers.org.

Speaker 2 (22:12):

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