Ep 99: The Future of Alzheimer's Trials: AI, Biomarkers, and Remote Research – John Dwyer, CEO of The Global Alzheimer’s Platform (part 2)

Ep 99: The Future of Alzheimer's Trials: AI, Biomarkers, and Remote Research – John Dwyer, CEO of The Global Alzheimer’s Platform

In part 2 John Dwyer, CEO of the Global Alzheimer's Platform (GAP), and BrainStorm host Meryl Comer discuss transforming Alzheimer's research and clinical trials. Dwyer shares how the field is shifting toward earlier intervention and leveraging artificial intelligence to improve trial efficiency and accuracy. AI can help identify subtle disease patterns and ensure trials enroll appropriate candidates. GAP is also pioneering remote, decentralized trials that bring research into patients' homes rather than requiring frequent clinic visits, aiming to dramatically scale up participation.

Dwyer also highlights proven lifestyle interventions that support cognitive health alongside pharmaceutical treatments and suggests multiple treatment approaches may soon be available.

This episode of BrainStorm is sponsored by Johnson & Johnson

Transcript

John Dwyer (00:00):

What we've learned from the fingers. Study, watch your diet, things that are proven to be genuine therapeutic solutions to the loss of cognitive ability, reduce your stress. You and I could work on that a bit more. These are real hard scientific results that we can embrace and advance.

Introduction (00:21):

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 (00:38):

This is BrainStorm. And I'm Meryl Comer. Our guest is John Dwyer, CEO of GAP, the Global Alzheimer's Platform. In part one, we discussed the real world impact of government cuts at the NIH on research. In part two, we focus on the promise of biomarkers in AI. I asked John about the research challenges of testing and treating people earlier across the Alzheimer's spectrum.

John Dwyer (01:05):

As your audience should know, in case they don't. I am not a physician. I am not a PhD, just a guy that's been in the trenches a long time. Our view is as the science gets more and more sophisticated, we are pushing the envelope in a positive way, try and treat people earlier and earlier in the symptomology or maybe not symptomatic at all, but as we go earlier in the process, we are dealing with the opportunity to actually give therapies to people that we haven't tested a lot on. So most of the studies that we do have historically been 60 and over of age, but now we're looking at studies that are going to start at 45 or 40 years of age. And we know that the condition of the folks who we're going to be working with is very different. Both their lifestyle issues, the stressors and their own physiology will be at a very different point in the cycle than they are at 60.

John Dwyer (02:05):

Big difference of 20 years from that point of view. So we're working very hard to anticipate what are the real drivers in gender for women, who by the way are as a statistical matter, a majority of women have Alzheimer's relative to men reasons that are not fully understood. But the numbers are what the numbers are. It is not 'cause women live longer than men. That gap regrettably, is closing and due to a variety of factors. Men and women are getting closer and closer to the same average life expectancy, but they still get Alzheimer's more. And so we focus on gender, but we're doing it on both sides of the house because when you deal with a 40-year-old male and start asking them about their cognitive health versus their underlying physiology, they too are seeing changes that are very real unexplored in the context of Alzheimer's disease and need to be at least anticipated. That's true of the co pathologies. There's a number of things that may be causing dementia that isn't Alzheimer's disease. And to detect them, you need to have a better sensitivity to underlying physiology that we hadn't studied that much prior to these recent years.

Meryl Comer (03:16):

John, the promise of AI to double trial speed and patient participation by 2030. What best supports gap's goal to improve the trial process and the patient experience?

John Dwyer (03:29):

So AI is here and I had my first AI air quotes around that 'cause it was so long ago. The AI people would call me out and say, that wasn't really ai but I had a natural language processing company in 2000, sold it to 3M and there are two things that I learned from that experience that are as true today as it was 25 years ago. One good data is critical. Garbage in garbage out is still a real problem with ai. 'cause if you have bad data to work with, you get bad patterns to recognize and you're teaching the machine the wrong lesson. We are striving in our portfolio of gap owned and operated trials to create relatively pristine and helpful data sets that will allow you to train AI on what are the true elements of early MCI or mild ad that might be detected with greater sensitivity and specificity by ai if it can read some early patterns and relationships out of clinical notes and electronic medical records or for that matter in interviewing people as you bring them in earlier and earlier in the process.

John Dwyer (04:41):

We've also been putting a lot of technology into these studies, emerging technology so we can see what technologies actually detect micro signals. Very subtle signals that if you collect all that data and really roll a AI algorithm over the top of it or create one actually you can be smarter about who's progressing or likely to be at risk of progressing in neurological disease. 'cause you're seeing little signals that we couldn't detect just a few years ago. So better data sets and more instruments that can measure subtle differences are two things we're really spending a lot of time on Meryl

Meryl Comer (05:22):

John. It turns out that the Achilles heel for a number of Alzheimer's studies that haven't worked or that the pool of patients in those trials weren't appropriate candidates for the therapies being tested. Can AI correct for that costly error?

John Dwyer (05:38):

I believe we've had studies as recently as seven, eight years ago that showed no meaningful clinical effect. And yet I think those underlying agents might have been very effective. We just had the wrong people in the studies. They didn't have disease or they didn't have disease at the progression that they, they were supposed to be testing them on. So the number one thing we're focused on is can we use AI to substantially improve the intake process? How we characterize people, how we put them to studies. And the big reveal here, Meryl, is to be bold about saying that person has a co pathology that could be influencing these results. Now maybe if we let them into the study or we don't let them into the study, that's not mine to decide today. I just want us to know that they have vascular dementia and maybe contributing to their condition or that they have elevated alpha synuclein and it contributes to their condition or any of a number of suspected causes that we can't detect yet, but we're going to be able to detect in the near future. And then we have to sort and decide what the weighted consequence that all is. That's where gap is going to be. We're going to recruit like crazy, try to develop trials for all those underlying conditions. But we're going to try to do our level best to make sure that the right people are in the studies for the therapeutic solution that we're testing that will do more to advance the discovery of treatments than anything else.

Meryl Comer (07:08):

John, isn't it time to make the caregiver and the patient active members of the remote trial team instead of just subjects? Does that strategy excite you at all?

John Dwyer (07:18):

It does. The research community and the science have been taking significant jumps in sophistication in that regard. There's a researcher at Wash U, well well-known who is showing data of remote micro sampling of you as a caregiver or the underlying person with suspected cognitive condition. And he's testing just a little each day and he samples morning, noon and night some days he only samples at various times that he doesn't get good signals at other times, but at a rate that is barely perceptible because they turn on their phone, they do literally a one, one and a half minute response and they're off about whatever else they're supposed to do. This is remarkable. It is my belief that we will get better insights into the underlying condition of people if we can measure them in their most comfortable setting their home around their most comfortable partner, husband, wife, family, and not bring them into a bricks and mortar site to do all that work on a one-off basis once a month. Very different experience and we can do such large numbers. We need to be doing, we had 185 studies in the Cummings report. We needed 35,000 enrollments to service that 185 studies that requires half a million screens on our current data. Only way to do that, Meryl, is get out in the remote, get into their own homes and do big numbers so that we're only bringing, bringing in people that are more likely than not to meet the requirements for the study.

Meryl Comer (09:00):

The clinic is artificial. I mean track us at home throughout the day. If you want real time and real life data. The care partner is often ignored when we're a wealth of information we'd be eager to share.

John Dwyer (09:13):

We're not alone, but we are hugely advancing the point of view of bringing the work to the participant, not the participant to the work. We've done that with community locations, now we're bringing it to the C communities more broadly, A completely remote clinical trial. We are actually going to be a site without walls and we're going to do everything without walls unless and until we have to actually administer the drug that has been tried in smaller scale. But with this particular sponsor, it is our anticipated hope and belief that we can do large numbers, high quality and work with our clinical trial sites to deliver to them people that they can then run through the meat and potatoes. Difficult to do high scientific impact work at the clinical trial site and we're not going to leave the sites behind. They will be partners in this clinical trial site without walls, but got to get bigger numbers right now. I think it's fair to say every year we do 20% of the numbers I gave you. We're lucky to do a hundred thousand screens. We're lucky to do 7,000 randomizations and the science is there. It deserves a chance.

Meryl Comer (10:25):

John Lee hear the promise of AI expanded trial networks. That sounds like the next generation of what you and your team envisioned for GAP back in 2015.

John Dwyer (10:35):

We are already in Europe. The United States is so far ahead of the rest of the world. We have to take good honest approach towards the rest of the world that builds on what we already know and doesn't expect to recreate the enormous infrastructure we've invested in here to conduct studies. So in our bio two study, for example, Meryl, we are testing something called blood spot technology. It's a little thin cardboard box. You open it, there's a little pin, literally just a pin. You prick your finger, you put a blood spot in three different places and it absorbs your blood drop literally a drop and allows for you to then close it and send it. And that delivery system will allow you to get the same outcome if we validate it and we believe it will, as you do with a blood draw.

Meryl Comer (11:25):

John researchers have had great success in demonstrating the accuracy of biomarker blood tests versus PET scans that are expensive and for many not covered by insurance. What are the implications globally?

John Dwyer (11:38):

That means I can take blood tests anywhere in the world that has a mail service, takes a little longer to get the results, but as we close the gap between big expensive technical things called pet images and get down to a blood spot being a comparable test because we've done such great work in showing the correlation between blood tests and pet, we close the gap. The technology's being offered to us. I think we're going to get there with cognitive testing before we get there with the blood plasma tests or PET in countries, not yet well invested in infrastructure. That's our gift to the rest of the world. If we can translate what we've learned into much more scalable technologies,

Meryl Comer (12:22):

What are the future projections for Alzheimer's global impact,

John Dwyer (12:26):

We may have solutions that are coming through that can bend that curve the other way. One of them is what we've learned from the fingers. Study, watch your diet, things that are proven to be genuine therapeutic solutions to the loss of cognitive ability, reduce your stress. You and I could work on that a bit more. These are real hard scientific results that we can embrace and advance and you and I have many friends who are out there pounding that message. Rightfully so. If you just improve your sleep and quit smoking, you add a lot of years to your cognitive life.

Meryl Comer (13:04):

John, you know many of us are into brain health while waiting for the science to catch up.

John Dwyer (13:10):

I know if I can get people to reduce their weight, get more sleep, quit smoking more exercise, and I give them one of these therapies, they're going to be better off therapeutic results, improve quality of life improves. We're going to extend their time to a higher quality of life. Whether you're on a therapy or not, you should be doing it. But the two together I suggest to you is going to be remarkable.

Meryl Comer (13:35):

John, in closing, what do you want the next generation of patients, researchers, and advocates to understand about the importance of participation in clinical trials?

John Dwyer (13:46):

My friend and partner in this endeavor, Merrill Comer, has for years said, walk into your doctor and get your baseline. Require your doc or your health system or public health to give you a cognitive baseline to provide you with whatever are the appropriate external blood test results that you can get for where you are in your journey. Get access to the things that we've just discussed that move the needle for your continuing high quality of life. Do those things and then as we bring big opportunities, smaller opportunities to enhance your conditions because they aren't all today's Alzheimer's. They're going to be tomorrow's neurological pathologies and we attack those. Watch the GLP ones, ladies and gentlemen. There's going to be an announcement of a major set of studies evoke and evoke plus the Novo Nordisk study on whether GLP ones have a cognitive effect and reduce the signs and symptoms of Alzheimer's disease.

John Dwyer (14:48):

And it may be a whole different mechanism of action that is remarkable in the fact we can even be talking about that. And if that is the case, bar the door, we've now got a two front war, we've got amyloid and we've got GLP ones, that would really be fabulous. How is coming? Five years ago, I couldn't have recited any of that. And don't be afraid to reflect on how you can move even one of those numbers. Hypertension, by the way, ladies and gentlemen, high blood pressure is probably the single most manageable in terms of we know a lot about that and no one disagrees with what I'm about to say next. If you can bring your high blood pressure down to what doctors say is healthy, everything gets better, including your cognitive condition.

Meryl Comer (15:34):

Our guest today has been John Dwyer, CEO of GAP, the Global Alzheimer's Platform fellow advocate, and one of the original four that joined George and Trish Friedenberg to launch UsAgainstAlzheimer's. Thank you, John.

John Dwyer (15:50):

Thank you for everything you do,

Meryl Comer (15:51):

Meryl, and thank you John for everything you do. That's it for this edition. I'm Meryl Comer. Thank you for brainstorming with us.

Closing  (16:02):

Support for BrainStorm by UsAgainstAlzheimer's comes from Johnson &Johnson. Johnson & Johnson is committed to creating a healthier future for patients where complex diseases are prevented, treated and cured. 

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