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Radical Approaches to Alzheimer's and the Journey to Curing It

April 02, 2019 00:00 AM UTC
- Updated February 18, 2020 14:21 PM UTC

Mei Mei Hu, United Neuroscience CEO, and Dr. Paul Alan Cox, Brain Chemistry Labs CEO, discuss their experience and research with Alzheimer’s and their approach to curing the disease.

Transcript
Maybe you are a Harvard trained lawyer who worked at a white shoe law firm, Uh, cravats or anymore? Paul, you're an ethnobotanist, which means you study at no botany. And yet the two of you have found yourself on the cutting edge of Alzheimer's research here. Really? Not only taking on some traditional science, but really innovating on that front. How did that happen? Maybe let me start with you. Um, yeah. I mean, a bit of admits that in the industry, I think, like most things, have you asked entrepreneurs sometimes So they really want do. And sometimes that's the course that life unfold. So for me personally, I never thought I'd be in Alzheimer's. Uh, we actually cut our teeth in animal health vaccines. So what did you tell me last night? Just to be very specific What you learned. What about that? About the pigs? That So we developed the vaccine platform and one of our first vaccines that we proved our concept with was basically immuno castration. So we're really good at cutting off balls of twine. And that's how we decided that we're gonna movinto Alzheimer's. So that's a natural progression. Exactly. Okay. All right. And Paul, how did you get into this? Uh, well, as Ethnobotanist working with healers and Sam Oh, I discovered a new major drug candid for HIV AIDS got very closely emotionally attached to the patient's. Once that was launched, moving a glacial speed through the pharmaceutical pipeline. I wanted to find something else, so we chose a less on Alzheimer's. In fact, the whole tangled diseases looking at a village in Guam where the poor Villagers have all the neuropathology of A L s, Alzheimer's and Parkinson's. And the symptoms, too. So just to talk about the tangle, so there are two hallmarks of Alzheimer's. You've got your amyloid beta amyloid, these clumps of protein that gather in the brain and aggregate. Another part of this is this neural fibula Larry Tangles called tau protein, and they also seem to be involved in killing their own. And yet, for all the really good science that we have on this, none of the efforts to tackle either of those problems has proved very effective. Paul. Yeah. I mean, there's been about 500 different clinical trials focused on trying to break apart amyloid. There's great mouse models that overproduced amyloid. So the ideas, if you could work in the mouth, can you bring in the clinic? And I think none of us taking enjoy that. Pfizer's out, Bajans out, Merc's out. Lily's out. I mean, not just their experiments failed there totally out of the Alzheimer's basis. So that's really concerning. Because Alzheimer's increase is increasing worldwide, it's becoming a major, major economic drain on societies with a dwindling demography like Japan or France on the poor. Patients air left wondering what's next. Let's put some numbers on this because it is really important. We have not seen the kind of failure that we've seen in our timers in any other drugs in any other disease setting. I mean, they're the success rate is something like 0.4% for drugs. There hasn't been a new drug approved since 2003 and most of the drugs out there where all the drugs out there don't actually deal with any of the underlying disease. They relieved some symptoms. You know, we have 215 active trials in this, compared to 7000 and cancer. This is a backwater. May may. No, it is. And, uh, sometimes I think it is useful to put a little perspective on it in terms of where we are with Alzheimer researcher. It's disappointing, especially with Bajans latest release. I think the amyloid hypothesis is taking a huge beating. I mean, I heard someone today saying, basically in the toilet, But if you take a step back and you think about how far we've come in a relatively short period time you realized it wasn't wind about 30 years ago that we actually understood and discovered the amyloid peptide, and it was only after 10 years after that that we had an animal model to work off of. So we really put it and think about it. I mean, we've come pretty far in 20 years from, you know, scientists always say that, you know well, we've come really far and we've learned a lot. This is you come here. It's a cholesterol, for instance. So cholesterol had a very similar path, you know, it took we figured out the molecule, we figured an animal model. We then figured out some epidemiology studies and the pathways, and then we started looking for inhibitors on it. That whole cycle took 100 years. So if you compare where we are with Alzheimer's toe toe, where other diseases have have big breakthroughs were there, we just have to work in the moment. So we feel really disappointed. But this is where we have to redouble efforts. So you started this company or your fun office company from you said your mom is a mad scientist as well, and you were working with her and you're working with your husband on this, But you spun this off to focus on amyloid. So this is the same protein that we were talking about that has failed in all these trials. But you have a different approach, very radically different approach, which is a vaccine. Talk a little bit about that. Yeah, we're kind of making the old school new school again, but, uh, what we have is a vaccine platform which basically teach your body toe produce antibodies against toxic proteins. We spun it out to focus on brain disorders. So, you know, we have employed and also tell and other proteins. And at the end of the day, you know, we're not at the end that you have to look at the data and go over the data tells you so. The science is still pointing towards amyloid being implicated as it may the major pathology and probably tower as well. We don't profess to have a silver bullet, but the field is telling us go earlier. So you look at the target and then there's different approaches. So earlier intervention ultimately prevention and probably in combination with other vaccines. I mean, I want to come to you in just a minute, Paul, but I just want to follow up in this go earlier part because this is the same pattern that we've seen in a number. Different disease settings. Cancer go earlier. Parkinson's go earlier. But how do you go earlier when we can't necessarily diagnose Alzheimer's that year? We'll interview but go for it. Um, you know, that's where the ecosystem comes. And there's a discussion this morning about diagnostics. And, um, you know, the field really depends on each other. So one we need better diagnostics to be able to predict who's going to get Alzheimer's, and we need also this better framework. A different model on howto creates and enable prevention studies or delayed onset studies that don't take 10 years or 15 years. So speaking of these different frameworks, so Paul, if we could see this cover of the story that Rick tests Ellie wrote about in Fortune on our cover. So there it is that's sold out in Wyoming. Wyoming Albert. It's actually it's a 7000 words story. It was the best traffic story of the month when it came out. A lot of people are interested. Here's for traffic. But you know, what I think people really gravitated to was the idea that you were creating a different research model for Alzheimer's in an area where you were bringing lots of different disciplines in and it created. You know, a consortium of global consortium of 50 different people with very different times is special. Well, I went around the world I call my John GALT speech. I've gone to the top smartest people. I could find 28 labs, 12 countries and I said, Look, you're a big deal. You've got an endowed chair. You've published book. She got medals when she said it all aside, come work of Wyoming on changing patient outcomes, impatient current patient lifetimes. And I think this is one of the problems is that we're looking at Alzheimer's through a focus of the limitations of the models because we have great models for AM Lloyd. We don't have models for town in Wyoming. We think amyloid and tau are not the causes of all climbers. We think their symptoms symptoms of a disease that occurs 20 years before people show any any cognitive deficits at all. We're looking at the very basic models of protein miss folding and find a way to stop him and the story that we wrote a fortune, which I urge all of you to read, read. It's really spectacular, but it took you to the comm aural people of Guam, where you were studying studying their diet and noticed something very unusual. We picked up a bacterial toxin and found that the people that had high levels of toxin had high levels of the disease. 25% of the Villagers were dying, but it's really the story of two villages. Then I found another village in the northern tip of Okinawa gamey, where they don't even have a word in their language for Alzheimer's. They never heard of it, and the people are 100 are have absolute Rico. I've never been around a geriatric population like this. What's the difference? We identified an amino acid, a dietary amino acid else hearing. We're now in phase two trials at Dartmouth Medical School, hoping that this could slow cognitive decline. We do know in a P 04 non human primates in ST Kitts, it totally slows down the neuropathology. So we're not looking for the silver bullet that will recover somebody. It's already in the depths of dementia. What we're looking at is a way to delay disease progression, slow disease progression and based on our face, one trial with a less patience. It looks like a high dose mean last therapy. We can get 85% slowing. If we could do that for Alzheimer's, we could make the disease push it off so it doesn't hit people until they're 90 or 100 that would be interrupting. You go ahead, I nto I'm gonna add to that, which is, I think one of the really cool things about what you're doing is actually super affordable as well. Yeah, this stuff costs $40 a kilo. Grams. It's one in the drinking water That's one of the challenges of nerd generation, particularly Alzheimer's, right And one, like you, said, the symptoms of the disease starts decades before you see the disease starts decades before your symptoms. Two. It's very difficult diagnosis, but three. These are massive populations. I'm just over five million people in the U. S. And over 40 million in the world. And so some of the stuff is coming down the pipeline. You have to think even if it works, is it practical? So, part of the idea of really coming up with the prevention, uh, something that you know, delays The onset of it is it has to be practical on a global basis. That's the way, and that's that's a great point. As you said, it's 5.7 million Americans now that are dealing with this around the world. That's much, much higher. But that cost of caring for people with Alzheimer's is about nearly $300 billion. It's gonna go up to 1.1 trillion if you believe the estimates by mid century. While it just came from Japan, where for every working person, every retired first, there's only two people working pharmaceutical firms are really interested they France, in the same way to 20.1 people working for every retired person. So the idea is we don't need another $400,000 a year Alzheimer's drug When you get on, that could be a a public health intervention across the world. And this is one thing that if if our thing is applications, that's a big if we know it's not toxic. If it actually slows and repeated trials, maybe it could help, even though it's not a silver bullet. But by delaying 5 to 7 to eight years, it might really help some of these countries right in a minute, just in a few seconds, I want to go to some questions. But before I do that, the police think. But maybe, you know, talking about public health interventions again. There is no better bang for the buck in public health anyway than a vaccine, which is the approach you're trying and so talk a little bit about how this vaccine works, because again, since it's not a virus that you're vaccinating against, it's harder for the body to actually find out what the thing they're supposed to protect against, especially since these proteins yourself, right? Yeah. I mean, um, you know, I'll be honest. The vaccine approach is not new. We've tried it before. The problem is, we couldn't do it safely or effectively. Um, So, really, what we're trying to do is when you say vaccine, it's just getting your body to produce and become the drug factory. So what? Our vaccine is fully synthetic. It's all artificial. And what we do is we, you know, we immunize you with it, and we teach your body to produce antibodies against the toxic forms of amyloid and tau and office knew Quinn. Um, and we do that because it's, you know, uh, endogenous protein. You know, you want to avoid an autoimmune response because that's one of the challenges of other vaccines. Um, and so our technology just happens toe work. Uh, it's not. It's not a new phase two. Now we have the space to finish basting. You have enough money to go to phase three. Uh, well, with some gaps that we gotta figure out before we're gonna face you gotta help in my eyes and make sure you get the highest. Probably a success when you go there. But that's one of the challenges. When you have a big badge in, you know, read out and the whole industry kind of just pulls away. And hey, are we Is this the right way to go? Right. But if you go to anyone and even pull because we're talking about this behind stage just like if you had the opportunity and option tohave aggregate employed in your brain or not, what would you say? Of course. So because we know that that that protein is clumping around neurons and killing it, killing them anyway. So whether it's the cause or a symptom, you just want to get rid of that. Do we have a commoner? Questions from the audience, Anybody. Okay, Um, so we'll keep thinking just this is a chance of a lifetime here, So But this does get to the issue of how science is done in America today. And you know what we've seen so many technologists come into on the data space, for example? You know, we've had several of of them on our stage entrepreneurs saying we're tired of how long traditional, you know, hidebound academic science takes, and we've got to break that model. So whether it's an Alzheimer's or something else, you know what you are we going to see more of this? Sort of, you know, crusading, You know, reb rebellious science from the outside. They both may, May and I were invited because we represent alternatives to the 500 failed trials. We need to have some sort of new approach, and I think it's time to look at a variety of different approaches and again our goal. And I think May Mays as well as to change the outcome of patients within their life. And that's what we're excited about it. Of course it's me. I've got Villagers that don't have Alzheimer's. They don't have any deficits whatsoever. And we've looked very carefully. Their diet. Maybe he's looking at a vaccine signed me up. I'll take it this afternoon. I mean, these were very alternative approaches, and the question is, each of the 500 failed trials cost big farm. About a 1,000,000,000 bucks a 1,000,000,000 bucks, they've dropped half a trillion dollars. How many times you have to keep doing the same thing over and over and over. We hope that maybe 510 will work or 511 but at this point we're both in phase two trials, and we're both contemplating How do we get into a phase three that's meaningful in a system that is really focused not on these alternative approaches. Yeah, One thing I think about the trial failures is you know, we learn something from each one, and we're approaching even something like that amyloid very differently than we did 10 years ago. I mean, the first efforts weren't safe, and then we had problems with dozing. And then we realized most of some of the patients that were dozing don't even have Emily in the breaks. Cary giving patients about the pathology, a drug that's supposed to intervene on the pathology. And now we're realizing, you know, going later is not the way to be. So you have to go the time of convention. So each one is something that we learn. And right now it's about threading the needle to find success. Um, I think one of the keys is actually taking and being open to perspective outside the traditional space. I mean, we're a motley crew of back sinologists originally, and we don't have a neuroscientist on the team. But we saw someone else's Bailey and say, You know, we don't know about the target of much, but we know how to design a vaccine that over different expertise. And so we've got a question in the back right here. You threw out several times the question of diet. Just take 30 seconds. Just summarize the data on the positive or the prevention side that leads you to have reason to believe that it may be dying well, there's broad indication that the Mediterranean diet reduces risk of Alzheimer's, and that's well accepted. We've been focusing on specific villages that have bad diets and good diets trying to see what's the difference. And it appears that from our work that one of the 20th dietary amino acids else hearing, if taken in sufficient dose, actually can reduce the formation of this neuropathology. And the reason we can say this is that we've does April 4 positive monkeys and ST Kitts, and we find that we can reduce their neuropathology of both amyloid and tau by about 85%. So the idea is that you carry within your head neuropathology. It's building up. You're asymptomatic Finally, you hit the point where there's nothing, no pathology. You start having cognitive issues. We and I think they made the same way. We would like to work very much earlier, maybe 20 years earlier, where we're working with a dietary amino acid if it really slows, uh, formation there a pathology people, potentially, if the FDA approved, could be taking this long before they ever developed symptoms. Lady. And I'll be your goal to get people vaccinated long before they develop symptoms. That's the ultimate vision. The last line of resistance silly story about you is the truth. Lies somewhere between science and story, listening and laboratory body and soul. And part of what you have really focused on is this idea that the laboratory is outside of the sort of four walls of that laboratory. Well, what's really help? This is We're doing this in a not for profit environment. I mean, I don't have quarterly shareholders. I don't have Mike showing up saying Why aren't you working on male pattern baldness? Yeah, you know, like late. Know that within a not for profit environment, we can take a deep dive. We can do things that are alternative. I assume you have certain same sort of of focus and doing something a bit different from the traditional path. Yeah, um, someone this morning was saying, you know, we're trying to see not where the puck is now, but where it's going. And the good news is, I feel like the industry is finally coming to some consensus that we have to go earlier. And they're realizing maybe not today or but eventually. Pretty soon we gotta go towards that that direction. The thing that sad is the great players Merc, Lily Fizer, Biogen are out there. Not just their experience. It worked. They're pulling out. Where do we have the major players That could help you and me if our move into phase three. And that's gonna be tricky. Yeah. You know, I think there's still some really good committed players out there. And that's what it takes to really make a breakthrough. Mei Mei Paul. Thank you very much for enlightening conversation. Thank you. Thank you.