The Longevity Formula

The Fire in the Brain: How Inflammation is Driving Parkinson’s, Alzheimer’s, and Long COVID | Cuong Do

• Dr. Brandon Crawford • Season 2 • Episode 44

Share episode

Send us a text

Is chronic neuroinflammation the silent driver behind modern brain diseases like Parkinson's, Alzheimer's, Long COVID, and mood disorders? In this eye-opening episode, Dr. Brandon Crawford speaks with Cuong Do, the CEO of BioVie Pharmaceuticals, who came out of retirement to tackle the growing challenge of neurodegenerative diseases. They delve into the intricate science of TNF-alpha, explore the concept of insulin resistance within the brain, and discuss the potential of next-generation neurodrugs, such as BioVie's Bezisterem, to not only alleviate symptoms but potentially alter the trajectory of aging itself. 

Join them as they unpack the significance of ongoing clinical trials, the implications of biological clocks and mitochondrial health, and the often-overlooked connections between inflammation and crucial aspects of health, including cognition, hormones, longevity, and even autism.

Key Takeaways

  • Many chronic conditions, including neurodevelopmental disorders and autoimmune diseases, may stem from fundamental light signaling failures at the cellular level.
  • In Alzheimer's disease, TNF-alpha drives the production of amyloid precursor protein (APP) and the phosphorylation of tau, contributing to amyloid plaques and tau tangles, though these may be downstream effects of inflammation.
  • Emerging research links the brain fog, fatigue, and malaise associated with Long COVID to inflammatory mechanisms that BioVie’s drug candidate, Bezisterem, aims to modulate.
  • Pre-clinical studies of Bezisterem in Parkinson's models showed it to be as effective as Levodopa in restoring muscle control and demonstrated a synergistic effect when used in combination.
  • Bezisterem is a small molecule that readily crosses the blood-brain barrier and has shown a long half-life, potentially offering benefits for Parkinson's patients experiencing "off" states in the morning.
  • BioVie is actively monitoring biomarkers of neurodegeneration, such as GFAP and neurofilament light (NFL), in their clinical trials and has observed a disruption in the typical correlation between disease progression and these markers in the treatment arm.

Resources

Products


Learn More
For more information, resources, and podcast episodes, visit https://tinyurl.com/3ppwdfpm

Dr. Brandon Crawford: I feel like there's a quiet revolution going on right now, and you are right in the middle of it. 

Cuong Do: A few years back, I came across a drug that I thought could become the first truly effective drug for Alzheimer's, the first new drug for Parkinson's in over fifty years. 

Dr. Brandon Crawford: The concept of microplastics, and how microplastics are being found in the brain, and then other studies showing they're found in testicles and other organs and things like this. 

Cuong Do: What those things could be the impetus that's leading to immune cells to

Dr. Brandon Crawford: Right,

Cuong Do: something off, which then ultimately leads to the inflammation that we're talking about here.

So that's why we believe this could become a very, very big deal.

Dr. Brandon Crawford: I'm curious, have you, had any type of experience with things like autism or, you know, any kind of demographics like that because I mean, we, we see a, a high autism population as well, and oftentimes neurological inflammation, brain inflammation is a huge component 

Cuong Do: Autism is one thing that I would love to explore one day because I totally agree with you that in my son's autistic. 

let's reduce the, the inflammation and see if we can reduce the battery repercussions. 

Dr. Brandon Crawford: Let's actually try and get to the root of what's driving this disease process. ​ 

 

Dr. Brandon Crawford: We used to think of inflammation like a swollen ankle or a sore throat. Something you could see, feel, fix. But what if it's happening where you cannot see it? Deepen the folds of the brain, and what if it's not just a symptom, but the root cause of what we call aging, memory loss, mood shifts, autism, Parkinson's, and everything in between.

That's what today's episode is about, the fire in the brain. Welcome to the Longevity Formula, the podcast where we explore a new era of wellness through the pillars of faith, light movement. Mindset, nutrition and science. I'm your host, Dr. Brandon Crawford. My guest is Kang Do a man who's lived at the intersection of Wall Street, big pharma, high tech strategy, and now the future of neuro health as CEO of BioVie Pharmaceuticals.

Kang's leading clinical trials that don't just chase symptoms, they go after the root cause, like inflammation in the central nervous system. Kwang, do thank you so much for joining us today. I'm very excited about this conversation. I.

Cuong Do: Brandon, thank you for having me.

Dr. Brandon Crawford: So I feel like there's a quiet revolution going on right now, and you are right in the middle of it. But what drew you into this space? Because you have a very, very intriguing background. You've done so many different things. How did you end up here? I.

Cuong Do: Well, it, it all started I, I was born in Vietnam. My family immigrated to the US at the end of the war. arrived when I was nine years old with $20 through our name and a change of clothes. And I did not speak English then. So that was the first priority. And when you have nothing, the best way to learn English is to watch as much TV as you can and read anything you can get your hands on. And this being the mid seventies was the advent of modern immunology as we know it. So somewhere along the way, I came across this topic, started asking all kinds of questions. Drove, don't find parents crazy. They, because they couldn't answer it. But my mom did work down the street. From the medical school.

So she just took it upon herself to take me around to see anybody that could that would be willing to spend some time with me. And somewhere along the way, there was a professor that was intrigued that this little kid was asking these kinds of questions. So he just took me under his wing. So I started working in his lab work, doing medical research when I was 14 years old.

Dr. Brandon Crawford: Wow.

Cuong Do: I eventually went out to Dartmouth College, got a double major about chemistry and economics. Got an MBA as well all in five years because I was in a I accepted a medical school. But while in business school, I realized I loved the knowledge in medicine, but not necessarily the practice of the research of it. And McKinsey, a large consulting firm, was building a new healthcare practice then. I ended up going to McKinsey where I helped stay for 17 years. And in the process helped build the healthcare, the high tech and the corporate finance practices with the firm as well. So my world has always been he healthcare and high tech. I eventually left McKinsey I was turning 40, Because by then, after 17 years, I was a senior partner at the firm. I didn't really wanna run anything there, so I knew I had to go and do something different.

Dr. Brandon Crawford: Mm-hmm.

Cuong Do: So since then, I've been a serial chief Strategy officer for large companies, starting first with Lenovo as part of the team that integrated the IBM acquisition, and then Tyco Electronics as Spark team that created Tyco Electronics when Tyco demerged into the three companies, then Merck. And as I was leaving Merck my friends at Samsung made another push to get me back to Samsung, to get me to Samsung. I've been saying no for a lot of years, but this time I couldn't say no because my good friend who's the son who's gonna become the next chairman of the group needed a lot of help and I will always help a friend. I

Dr. Brandon Crawford: Right.

Cuong Do: proceeded to spend seven, seven years commuting back and forth between New Jersey and Seoul every other week to help lead the global strategy group for all of Samsung.

Dr. Brandon Crawford: Wow.

Cuong Do: And along the way I've also started three biotech companies with my brother. So we had a, we discovered a drug for Pompe disease in our first company. a nice exit there, and we've been reinvesting that into starting new companies. I also actively invest in new biotech startup and serve on boards. And that's how I got to BioVie. BioVie was started by a business school classmate who came asking for help. Like I said, I always help a friend. I put in something early, money into the company was on the board to shepherd through our program in liver disease. And that's the, that's the origin of the company. a few years back, I came across a drug that I thought could become the first truly effective drug for Alzheimer's, the first new drug for Parkinson's in over fifty years And so I orchestrated the acquisition of that from my board role. the last condition for the deal was I had to step in as CEO.

So that's why I am doing what I I've always said I would never do. We just be CEO of a public company.

Dr. Brandon Crawford: So long story short, I need to become your friend so that if I need something, I can reach out.

Cuong Do: Well, I consider myself to be very, very lucky because for me, this is very much a personal cause.

Dr. Brandon Crawford: Mm-hmm.

Cuong Do: My, my father's memories going, A dear cousin just passed away from Parkinson's, and I consider to be, I, I consider myself to be a very lucky person because I am fortunately in am in a position to go and try to do something about it.

And that's why I came back from retirement to, to do this

Dr. Brandon Crawford: Yes.

Cuong Do: And hopefully this will help many, many other people. When we're with Five Quest.

Dr. Brandon Crawford: Absolutely. And, and I mean, I'm thoroughly convinced that it will, you know, I was looking through the pipeline that you guys have or are developing in BioVie and my gosh, I mean the, the you know, the two products that I looked at I mean, if they're really doing what you guys are saying that they're doing, which I want to talk about your clinical trials.

I mean, this will be. the beginning of a revolution for these neurodegenerative diseases. I mean, this is amazing. So you do have true two clinical trials going on, correct.

Cuong Do: We do we have just initiated two clinical trials. One is in where we are giving our drug candidate Bezisterem serum to Parkinson's. Patients who need to go onto therapy for the first time to address their symptoms. Okay. And the second trial is in long covid. As you may know, there's nothing that's available and works for long covid

Dr. Brandon Crawford: Great.

Cuong Do: and that's why we've received a grant to go and explore long bether in long covid, and we can explain the mechanisms and why this all are related, you know, over the course of our conversation today.

Dr. Brandon Crawford: That's amazing. So are these clinical trials are going on right now, correct?

Cuong Do: Yes, they are going on right now. You can find out more about our trials by going to our website, BioVie pharma.com. And there there are links that will take you to the specific sites for those two trials. They'll tell

Dr. Brandon Crawford: Absolutely.

Cuong Do: what we're trying to accomplish in a trial and we'll eventually we'll have the map of all of the the sites that are available.

Dr. Brandon Crawford: I was actually looking at that not too long before we jumped on here. And so, at the heart of everything that you guys are trying to accomplish it's really circling around this concept of inflammation, correct?

Cuong Do: Yes, I think you've nailed it. With your introduction, we believe that inflammation is the starting point for a lot of things that go wrong the body But It also has to be taken in context. First of all, inflammation is just a natural part of how the body works, right? When we have an infection, for example, immune cells kick in to try to ward off the infection, and as they work, they release various inflammatory factors such as TNF Alpha.

And so that creates the inflammation that leads to the swelling that you see and other things, right? So it does play an important role, as you mentioned, right? But luckily when the infection has been warded off, the immune cells go back to normal and they and the inflammation subsides. how things are supposed to work. But unfortunately, we also put ourselves into situation that is not exactly great for our body through our diet, lack of exercise. Exposing ourselves to various toxins and environmental factors. The body is fine that it's constantly trying to ward off something. So when your immune cells are constantly working at some level, it's constantly producing TNF alpha. So you have a situation known as chronic low grade inflammation, where TNF alpha is constantly there. And TNF alpha is known as the master regulator, master regulator. Inflammation. So it's the starting point that then triggers a lot of other things to happen. First of all, it perpetuates itself, right?

So when you have TNF alpha, it then releases other things that leads to more production of TNF alpha.

That's the first starting point. The second is that it actually drives insulin resistance. And once you have insulin resistance, you actually, it's associated with diabetes, of course, right? But it's also associated with Parkinson's because two things need to be present at the same time.

For a person to develop Parkinson's symptoms, the first is you need low dopamine in the brain,

Dr. Brandon Crawford: Mm-hmm.

Cuong Do: then the second is you need insulin resistance. If somehow you can reverse. Address the insulin resistance in the brain. The body then is able to use the both levels of dopamine that's there to restore muscle control. But unfortunately, no one has ever figured out a practical way of doing that until now, until that's what we're trying to do with Bezisterem. So insulin resistance as it relates to Parkinson's Alzheimer's, right? TN alfalfa drives a lot of other things, but it also does two things that many people may may be aware of. It creates. It drives the production of something called the amylin precursor protein or a PP, which then leads to def formation of amyloid and amyloid plaques. And then the other is that it drives this kinase phosphorylates tau into become phospho tau,

Dr. Brandon Crawford: Mm-hmm.

Cuong Do: then aggregates to, to create tau tangles.

I believe those are. Symptoms or down downstream effects of inflammation in, in Alzheimer's. I do not believe they cause Alzheimer's, but they are the signals by which you see that the Alzheimer's been progressing

Dr. Brandon Crawford: Right.

Cuong Do: And then in long covid, nothing works for long covid. And in recent years couple of years, many more and more researchers are tying the long covid symptoms of, brain fog fatigue and malaise to inflammation that works through exactly the same mechanisms that our drug candidate Bezisterem modulates. And that's why we've received a grant to go and explore Bezisterem in long covid, right? so, it's all about inflammation as it starts with TNFa.

Dr. Brandon Crawford: That's very intriguing and, and connects a lot of dots. I'm curious because I see a high degree of neuro autoimmunity in the Parkinson's population and sometimes in the Alzheimer's or dementia population. Do you think that. One potential mechanism of action is not just suppressing inflammation but modulating it here.

So to restore that balance in the immune system as well, and downregulate the autoimmunity.

Cuong Do: It, it is possible. We don't have any data to speak about that for, for certain,

Dr. Brandon Crawford: Yeah.

Cuong Do: A plausible explanation is by essentially dampening the TNF alpha effect, you're actually helping to restore immune so I think your comment, it may be possible

Dr. Brandon Crawford: Yeah. That's awesome. And then my, my next thought revolves around mitochondrial function. Are you guys looking at how your products have an impact on the mitochondria? And there's various ways, you know, to measure it. So I don't know if y'all are doing, you know, any of that, maybe even looking at PGC one alpha or, or anything like this.

Cuong Do: We're not looking at it very directly. But one would hypothesize that that exactly what's going on, there's

Dr. Brandon Crawford: Yeah.

Cuong Do: Effect that would have on various organelles within the cell, right? So mitochondria would be one of a an er. Stress is another aspect of of inflammation.

Dr. Brandon Crawford: Absolutely. Well, you know, so. Like I said, I've, I've worked with various degrees of Parkinson's and we have a certain, you know, exam process and certain labs we like to look at and whatnot. It is common that we find very high levels of environmental chemicals, heavy metals, these types of things in this population as well.

Interestingly enough, I was reading a study that came out not that long ago, and it was talking about. The concept of microplastics, and right? And how microplastics are being found in the brain, and then other studies showing they're found in testicles and other organs and things like this. How, I'll just say this.

What in the world do we do with this information? I mean, is this something that we can, you know, leverage ourself against? Is this something we protect against? Is this, so do we just fight the inflammation here? What are your thoughts on this?

Cuong Do: What those things could be the impetus that's leading to immune cells to

Something off, which then ultimately. Leads to the inflammation that we're talking about here. So unfortunately, I think the, until therapies become available, the only thing that we can really do is to try to minimize our exposure to these things,

Dr. Brandon Crawford: right.

Cuong Do: better diet, try to remove these exogenous factors from our environment, right? And that's

Dr. Brandon Crawford: Absolutely.

Cuong Do: only solution at this point in time.

Dr. Brandon Crawford: Absolutely. And, and you're right in, in Parkinson's, right? We see the the loss of the, the neuro melanin within the substantial nigra and our focus, right? So I'm a, I'm a big photo biomodulation guy. I've developed lasers. I've, you know, I'm, I'm very specific about how certain wavelengths of light can drive you know, things like Palm sea and lead to increasing.

Melanin and, and all this kind of stuff. And so, are you guys actually restoring some of that neuro melanin loss or is it more of a concept of you know, reducing the inflammation allowing the body to then utilize what it has left.

Cuong Do: Yeah, what we hope to show over time. We're actually modulating or modifying the progression of the disease. Now, let me

Dr. Brandon Crawford: it.

Cuong Do: some data of what we saw preclinical studies, in rodents and in non-human primates, right? What we found is that our drug candidate Bezisterem was equally as effective as levodopa. in restoring muscle control. Now, if that's a huge deal, as you know, right?

Dr. Brandon Crawford: Absolutely.

Cuong Do: it, it levodopa remains the standard of care five decades after it was introduced because nothing else has been able to replace it. here we are. It's equally as effective as levodopa alone, right? when you gave the combination of Bezisterem and levodopa, you saw a synergistic effect.

You actually saw the maximum muscle control. But here's the real kicker. When at the end of the study when we sacrificed the monkeys and looked at their brains, we found that those treated with Bezisterem retained twice as many dopaminergic neurons as

Dr. Brandon Crawford: Perfect. Yeah,

Cuong Do: Bezisterem suggesting that there's a neuroprotective property to the drug, which to us is actually not at all surprising, right?

Because we know Bezisterem reverses insulin resistance. Which means there's greater glucose availability

Dr. Brandon Crawford: Mm-hmm. Mm-hmm.

Cuong Do: know from imaging studies that it increases blood flow to the brain as well. Which means there's greater oxygen availability, right? So when you have more oxygen and glucose in the brain, that only bodes well for better neuronal health, right?

And so that's what we're ultimately good trying to show in the studies, right? The one that we're kicking off right now is getting at the short term aspect of it, showing that we can actually help. Maintain control in the short term, right? So we're giving patients Bezisterem alone for three months and comparing 'em to those treated with a placebo to see what happens to their ability to maintain muscle control. But when we fully develop this, we would study patients for 12, 18 months and see if we're able to modify the progression of the disease, right? So that's why we, we believe this could become a very, very big deal.

Dr. Brandon Crawford: No, that that is a big deal. That's huge. While ldo L-DOPA can, can absolutely, you know, have a significant impact, but then the issue with. The continued use of L-DOPA is you can potentially develop tardive dyskinesia. So I'm assuming that what you're trying to do is, number one, not develop that, or if you do, to make it to a lesser degree.

Is that what you guys are seeing?

Cuong Do: That we believe nothing that we have seen to suggest that Bezisterem could lead to target to any form of

In fact, in studies, in think, when we gave the monkeys, the combination of Bezisterem and levodopa, we saw a reduction of lid. We saw a reduction of the, of dyskinesia, right?

So

Dr. Brandon Crawford: Wow.

Cuong Do: a big deal. 

Dr. Brandon Crawford: Yeah, that's a huge deal. I was, I was looking through the schematics and the different you know, mechanisms of your products and it, it kind of reminded me of some of the literature that I've read about the GLP one. Drugs out there. I don't know how much overlap there is in those mechanisms, but obviously, you know, the GLP ones are going to help with insulin sensitivity.

It's, it's very anti-inflammatory and whatnot. And, and I have seen people that have con cot use with the GLP ones and they have something like Parkinson's or dementia or something like that. Historically, from a clinical perspective, we've seen that that can help that individual. And I'm wondering if y'all have had any of those discussions with how there is some kind of overlap here with the GLP ones and maybe some similar mechanisms going on.

Cuong Do: I, I think it's related, right? Because as you know, as you said GLP one does have an impact in some sensitivity.

Dr. Brandon Crawford: Mm-hmm.

Cuong Do: but it's a downstream effect

Dr. Brandon Crawford: Yeah.

Cuong Do: and

Dr. Brandon Crawford: Yeah.

Cuong Do: reason why I, I believe one of the big pharma companies have had a very large, very long study with a GLP one trying to see if there's an impact on Alzheimer's, right?

But I think what's going on is that the signal there is a very small signal, and that's why

Big studies and lung studies to try to eek it out. Whereas here, we believe that this is a very direct impact. On insulin sensitivity, and that's why we believe that's the reason why we've seen the bigger impact that we've seen so far.

Dr. Brandon Crawford: Gotcha. Awesome. I'm curious, have you, had any type of experience with things like autism or, you know, any kind of demographics like that because I mean, we, we see a, a high autism population as well, and oftentimes neurological inflammation, brain inflammation is a, a huge component of that.

Cuong Do: Yeah.

Dr. Brandon Crawford: it's a smoking gun, you know, sometimes, sometimes not.

Sometimes it's like a, you know, a secondary, you know, effect or whatever. But, but have you guys had any type of experience in that demographic as of yet?

Cuong Do: We have not, right? As a company or company sponsored trials. Have really focused on Al on Alzheimer's, Parkinson's, along Covid. With that said, we also have a policy in place whereby we will support various investigator initiated trials. if there's an investigator that has a hypothesis to how Besi sternum could affect a, a disease arena. are not currently exploring, we will work with that investigator. We will support by providing drug for free to essentially allow the investigator to go and test a hypothesis, right? We've done that with things like traumatic brain injury so forth. Autism is one thing that I would love to explore one day because I totally agree with you that in my son's autistic. I totally agree with you that there is an inflammatory component of this in Europe. Who knows if it's causative or it's down side effect of what's really going on. But the reality is inflammation is there. It's causing downstream repercussions. So let's

Reduce the, the inflammation and see if we can reduce the battery repercussions.

Dr. Brandon Crawford: Exactly. Yeah. And, and that's ultimately, you know, what we're, we're trying to do over here is try to eliminate any kind of metabolic roadblocks like we call them, whether it be inflammation, autoimmunity. Whatever that may be. And then we try and build plasticity in the brain, so to improve functional skills, et cetera.

And so that's kind of the approach. And so that, that's really what, what I'm thinking. I mean, this sounds like a very, you know, I. Logical step in the right direction. So I'm excited. I'm, I'm definitely gonna take a look at it a little bit more and, you know, read more about the pharmacokinetics and see how this could potentially fit in because it, it definitely sounds like a good potential here.

I think it's great, so,

Cuong Do: Yeah. That's

Dr. Brandon Crawford: mm-hmm.

Cuong Do: why we've really liked the profile of this drug compared to the other drugs that have been approved, let's say for Alzheimer's and for Parkinson's. So Bezisterem is a. it's a small molecule that freely crosses the blood brainin barrier.

Dr. Brandon Crawford: Hmm.

Cuong Do: you take one capsule in the morning and one capsule at night.

So it has a pretty good half-life out there, which in Parkinson's is a big deal, right? Because as you know, l-DOPA has a relatively short half-life.

Dr. Brandon Crawford: Yes.

Cuong Do: consequence of that is that when Parkinson's patients take their evening medications and go to bed. Often when they wake up in the morning, their muscles are in the off state.

They have, don't have control of their muscles. They're rigid, they can't move. And so they have to take their morning meds and wait an hour so that they, until they get the control of their muscles right, that's part of the reason why you don't find, parkinson's patients wanting to schedule things first thing in the morning is because it just takes them time

Dr. Brandon Crawford: Yeah.

Cuong Do: take the drug and for things to kick in to get out of bed. In contrast, in a trial that we ran where we gave Parkinson's patients with moderate to severe Parkinson's patient Parkinson's, we gave them Bezisterem and L-DOPA in the morning, about a third of those patients were able to get out of bed. And you know, that's all because of ster, because they had the long half-life.

They, they, we were able to get outta bed despite the fact that El Dopa has already worn enough. Now that's a huge deal. 

Dr. Brandon Crawford: That is a huge deal. Yeah, that's a huge life changer.

Cuong Do: Yeah.

Dr. Brandon Crawford: I used to work with, I won't say his name, but I worked with him for a very long time. He had Parkinson's and I mean, I, I probably worked with him for close to a decade and, and we had huge improvements in him, but you're right, the mornings were just awful.

And we got to where we couldn't schedule an appointment with him in the morning just because we had to give him time to get up, take his medication, get moving around. I mean, he loses half the day, you know? So that alone is is just huge reason to take it for sure. I. So I'm cur, I'm curious, so what about just the concept of longevity, right?

Everyone wants better health span. Everyone wants better lifespan, right? I'm more of a, a health span guy, right? I want my years on this earth to be as active and productive and joyful and, you know, full of fun and all the things, right? Lifespans great. But if those additional years that we squeeze out are not fun and exciting, who really cares?

So I'm more of a health span guy. But I mean, we all, I, I think it's pretty agreeable that, you know, I don't think we'll find anyone that says inflammation is not at the heart of aging and, you know, debilitating issues and all these types of things. So. Is this a potential way to just live better and potentially longer?

Are y'all looking at this? What do you think?

Cuong Do: We absolutely are. But explain this, let me give an analogy,

Dr. Brandon Crawford: Okay.

Cuong Do: right? If you think about A DVD, for those of us who are old enough to remember DVDs, right? When you take a DVD out of the package for the first time, it is pristinely clean.

Dr. Brandon Crawford: Mm-hmm.

Cuong Do: into the player, the laser has no trouble decoding the information on that disc.

So as a result, you get great pictures and sound on the playback. But if you use that disc over and over again, over the years and over the decades, you'll get fingerprints, smudges on it, scratches and so forth. So as a result, the laser actually has difficulty reading through all that Gump, And that's why you get the skips and stutters

Dr. Brandon Crawford: Mm-hmm.

Cuong Do: whenever the disc is dirty. Well, the same thing happens in our body, As you know, everything in our body is encoded for by our DNA and our genes. And as we age, there's a natural process called DNA methylation that takes place whereby different methyl groups gets added to the surface of our DNA. So think of it, this is the equivalence of fingerprints and smudges, like the gunk builds up on your DNA. And after a while, as it accumulates the molecules that are responsible for decoding our DNA can't read through. And that's a result you get mis decoding of DNA. And that's why this hypermethylation of our DNA has been associated with a large number of diseases, particularly related diseases. I give you all this background because in our Alzheimer's trial, took blood samples from patients at the end of the study and we analyzed it for DNA methylation, right? And the extent of DNA methylation can be measured by a number of what are called biological clocks, or DNA methylation

Dr. Brandon Crawford: Mm-hmm.

Cuong Do: We analyzed it and we found that those patients that were treated. With Bezisterem had about a four to five years age deceleration advantage, composed the dose that were on placebo.

Dr. Brandon Crawford: Wow.

Cuong Do: you get too excited and think that's reversing aging or some, or the fountain of you, if that's not it, what it really, what we're saying is that Bezisterem is able to modulate. The degree of DNA methylation the tune of what, four to five years? And so to your point earlier about health span, imagine if you could live four to five years healthier as we all age. And, and by the way, Bezisterem is the only drug that we know of that has been able to show in a clinical trial that it has an impact of DNA methylation in a manner that's side to disease. And

Dr. Brandon Crawford: right.

Cuong Do: taken that understanding down to almost a, a molecular and gene level. We understand how Bezisterem activates certain genes and the genes that it, it has an effect on Alzheimer's, Parkinson's, a LS, diabetes and many of these things that we've just been talking about before. So inflammation absolutely has an impact on, the aging process, the biological aging process in my, in my opinion, and what we've seen so far in the data. And, but frankly, I have no idea we can develop a drug to do that because the FDA does not consider aging to be a disease,

Dr. Brandon Crawford: Correct. Yeah.

Cuong Do: And so we're still talking to various experts or collaborators and so forth.

And I think the only thing that we can possibly do is just to go and show that it has an impact on a number of different age related diseases and hopefully. of them that people can say, well, there's a pattern here, right? We'll see what happens.

Dr. Brandon Crawford: Absolutely. Well, I mean, it, it sounds amazing. I want to grab some of this stuff, like I, I definitely want to, we're gonna talk offline here a little bit, but, have you guys noticed any type of side effects with taking this? What have y'all seen?

Cuong Do: The number one reported side effect is a mild transient headache.

Dr. Brandon Crawford: Okay.

Cuong Do: It disappeared after about a day. Remember, it increases blood flow to the brain, so

Dr. Brandon Crawford: Mm-hmm.

Cuong Do: create a bit more inflammation. That's why you have a headache reported by fewer than 10% of

Dr. Brandon Crawford: Okay.

Cuong Do: right?

Dr. Brandon Crawford: Wow.

Cuong Do: is a relatively safe based upon what we have seen so far,

Dr. Brandon Crawford: I'd say so.

Cuong Do: one reported side effect is a mild headache.

Dr. Brandon Crawford: I get a headache just going to work some days. So, so, all so yeah, I'm, I'm just getting more and more curious about what you're telling me here. Have you guys looked at things like hormone profiles or even looking at just major inflammatory markers like homocysteine, crac to protein, the apo, lipoproteins, any of this kind of stuff to see it, because a lot of hormone challenges can sometimes be inflammatory based as well.

Cuong Do: We've spent less time on hormones than other, biomarkers, right? The usual biomarkers associated with meta me metabolics and so forth. But the, the thing that we've started looking at more recently are gf GFP and neuro GFP and neurofilament light NFL, right? Those are biomarkers of neurodegeneration,

Dr. Brandon Crawford: Mm-hmm.

Cuong Do: And so that is part of all of our trials. Now, we're just collecting more and more data on Bezisterem effect, on GFAP and NFL.

Dr. Brandon Crawford: So on your neurofilament testing 'cause we're monitoring this in a a LS patient right now and we, so we do various regenerative medicine procedures and we seem to have found, you know, a a, a really amazing proprietary, you know, protocol and dosing strategy, et cetera, where we're actually seeing this neurofilament.

Testing actually reverse. Like we're, we're seeing like huge improvements now that we're, we're doing this. Are you guys monitoring this for all the different neurodegenerative diseases or, yeah. And, and I'm assuming you're seeing Okay. I'm, I'm assuming you're seeing positive trends in that regard.

Cuong Do: We're seeing the data that we've seen so far shows that there's a disruption in the trend, right? Because as you know, the the data, the data from our placebo for example, shows a near perfect correlation between progression of the disease and levels of, of both NFL and GFAP,

Dr. Brandon Crawford: Mm-hmm.

Cuong Do: And what we've seen in the treatment arm. That relationship disappeared. In fact, it becomes flat. It becomes flat regardless of the progression of of the neurodegeneration. In this particular case, Alzheimer's was the trial, there was no increase in gf GFAP

Dr. Brandon Crawford: Right,

Cuong Do: NFL.

Dr. Brandon Crawford: which is good,

Cuong Do: we're still working to try to figure out exactly what that means and how, how

Dr. Brandon Crawford: right?

Cuong Do: build upon that.

We're continuing just to collect more data.

Dr. Brandon Crawford: Absolutely. Yeah. One, 100%. What about something as you know, I don't wanna say, you know, every day, but what about things like hypothyroid? Have you seen how you're having an impact on the thyroid?

Cuong Do: we have not, I don't recall having seen any data on that. That's not something that we're actively looking at

Dr. Brandon Crawford: Okay. That's amazing. So let me ask you this. It might be a difficult question to answer, but in all the things that you guys have been looking at, all the different trials, all the different anecdotal, the A data, all this types of stuff has there been anything that really just jumped out and grabbed you and you went, oh my gosh, this was not expected, but this is freaking amazing.

Like, have you experienced anything like that with these drugs?

Cuong Do: I can't say we have, because we had such high expectations of on what these things could

Dr. Brandon Crawford: Yeah.

Cuong Do: For example, in our Parkinson's trial we were looking purely at muscle control,

Dr. Brandon Crawford: Mm-hmm.

Cuong Do: pleasantly found non-muscle, non-motor impact,

Dr. Brandon Crawford: Sure.

Cuong Do: So essentially patients started saying that they actually could sleep better,

Dr. Brandon Crawford: Hmm.

Cuong Do: restless leg symptoms are significantly down and so forth. But if you kind of think about it, they're somewhat related too, right?

Dr. Brandon Crawford: Yeah, absolutely.

Cuong Do: yeah, we weren't looking for it, but we found it in the data.

Dr. Brandon Crawford: What about gut motility, because that seems to be a big challenge in Parkinson's as well. Was there any change in that or any reports of change in that?

Cuong Do: we, we did not look for that.

Dr. Brandon Crawford: Okay. I would think, right? I would think that as you continue working with that demographic and you're modulating inflammation and improving muscle tone, muscle mobility even just having the person be able to move better is going to be you know, having a positive impact on peristalsis and gut motility.

So, that's just usually a, a huge complaint that you know, people present with in our practice, when, when they have Parkinson's or even early stages and whatnot. So. Okay, so let's, let's pretend that you have a group of medical students around you, right? These, these are fresh years. They haven't been indoctrinated yet, right?

And they're about to go off to med school and learn how to start saving people. What is something that you would want to communicate to this demographic about, you know, about to go out and start treating the world?

Cuong Do: I think the most important thing is a decision quickly. Not making a decision isn't making a decision itself, right? So just think about ER rotation. Your patient is there, he or she's bleeding out, right? Something needs to be done. are you gonna do about it? And I think the mistake many young, early students make is you could try to go and do all the right things, right?

You list out all the tests, these are all the things you wanna do. But the reality is by the time you get it all back, your patient could be dead. And so what are you really going to do? So focus on the few key things take, allow you to take the first step,

Dr. Brandon Crawford: Yeah.

Cuong Do: And then the, after taking the first step, it buys you time, buys your patient time to take the next step, right?

And so forth. So make a decision, make it quickly.

Dr. Brandon Crawford: Absolutely. Yeah, you're right. I mean, these patients in front of us, they're, they're hurting. They're hurting, their families are hurting. They need help. And I'm just really thankful that people like you are out there in the world and really just thinking outside of the box and really being willing to kind of buck the system a little bit because that's, I mean, that's really what you guys are doing.

I mean, you're, you're getting outside of. The traditional paradigm and you're saying, well, let's not just cover up a symptom. Let's actually try and get to the root of what's driving this disease process. So I really appreciate that. And you're absolutely right. You have to take action. I would definitely echo what you just said.

Are there any closing remarks or any concepts or big ideas or anything that we didn't touch on that you would like to throw out to the audience today?

Cuong Do: Now I think it's just. Take the road less travel. I mean, Frost was absolutely right? If the road that you're on right now doesn't give you the solution that you are looking for, take the road less travel, And try something different. Try something new. And

Dr. Brandon Crawford: Yeah.

Cuong Do: we're doing here with BioVie, right?

It's just everybody thinks we're crazy. Nobody really believes that this is actually what's going on. Partly because, the number of articles that have been published on amyloid and it is in hundreds of thousands, right? And the number of articles around inflammation in Alzheimer's, for example, is in the thousands, right?

There are people out there who believe in it, who understand it, but it's just drown out, drowned out by the mass that's out there, right? So take the road less traveled, really, and, be open-minded about perhaps there's something else that's going on the conventional wisdom says.

Dr. Brandon Crawford: Absolutely. I, I, I'm reminded of a quote, I think it is Carl Young, but he basically said, and I'll paraphrase. If the path in front of you is clear and easy, you're on someone else's path, right? Oh my gosh. Okay, so for everyone listening that is going to just naturally want more information please give my audience information about, you know, can they enter a clinical trial?

How can they connect with a doctor to start using these products? So what do they need to do?

Cuong Do: If you want to learn more about what we do, please go to BioVie Pharma. That's B-I-O-V-I-E pharma.com. There you'll learn much more about our drug mechanism of action and so forth, but you will also find a page on clinical trials that is the place that will give you the information about, but the trial, what we're trying to show, and as we launch more and more sites. You can go there and consider going to a site. In Covid, we essentially would have something close to 20 sites when fully launched. Right now I think we have two or three, right? So we're constantly standing up new sites every day Parkinson's. Interestingly, you can actually participate from home, right?

Dr. Brandon Crawford: Wow.

Cuong Do: a major city, we can send people out to you. Allow you to participate from home. this Parkinson's trial, please recognize that this is only for diagnosed Parkinson's patients who have not been on therapy before. So patients who need to go onto therapy for the first time to control their symptoms. And that's the trial that's that we're trying to recruit for right now.

Dr. Brandon Crawford: Perfect. Okay, great. That, that's amazing. Well. I really, truly appreciate you for thinking differently. Not only that, but for building the systems that back this up, right? So for those listening you know, if someone is dealing with Alzheimer's, Parkinson's, long COVID. Any of these things, please check out the BioVie  clinical trials as Huong just described, we'll put the information in the show notes.

Everyone else stop waiting for diagnosis. Start changing your environment, changing your brain, start listening to your body and speaking the right language. Everyone, thank you so much for listening. Kondo, thank you so much for. Your wealth of information. This has really started, you know, my gears are turning quite a bit and I'm gonna talk to you a little bit offline here, but I'm, I'm really thankful for you, thankful for your work, and thank you for helping the world.

I so appreciate you coming on today.

Cuong Do: Thank you very much, Brandon for having me here. It's been a pleasure. 


People on this episode

Head Shot

Dr. Brandon Crawford

Host
Head Shot

Cuong Do

Guest