Talk of the Towne episode 09: BrightFocus Foundation

The latest episode of Antidote’s quarterly podcast series Talk of the Towne is available now! Talk of the Towne is focused on bridging the gap between clinical discussion and patient centricity, hosted by Antidote’s Senior Clinical Informatics Manager, Dr. Richard Towne, PharmD.

Our latest episode features Nancy Lynn, the Senior Vice President of Strategic Partnerships at the BrightFocus Foundation, one of the members of Antidote’s partner network. For the past 50 years, the BrightFocus Foundation has funded worldwide research to defeat Alzheimer’s disease, glaucoma, and macular degeneration, in addition to providing resources and support to patients and their loved ones. Rich and Nancy had an energetic discussion about her work at BrightFocus, with a special focus on recent research breakthroughs and Alzheimer’s clinical trials. Give it a listen or read the transcript below!

Talk of the Towne episode 09: BrightFocus Foundation

Rich Towne:
Hi everyone, and welcome to Talk of the Towne, the podcast from Antidote that bridges the gap between clinical research and conversation. I'm Rich Towne, a trained pharmacist, and the senior clinical informatics manager at Antidote. Today, I'm thrilled to welcome Nancy Lynn, the senior vice president of Strategic Partnerships at the BrightFocus Foundation, one of the members of Antidote's partner network.

Nancy has worked with BrightFocus since 2016 where she has facilitated and stewarded mission-based partnerships and to increase public awareness of Alzheimer's disease, macular degeneration, and glaucoma. She also worked on the award-winning Alzheimer's related film, Glen Campbell: I'll Be Me, and is the executive producer for James Keach's documentary, Turning Point: The Quest For A Cure, which captures the human side of the search for Alzheimer's disease breakthrough. Welcome to the show.

Nancy Lynn:
Thank you, Rich. Yeah. We're actually working on a new documentary, almost finished now with Lauren and Seth Rogen, which will be called Unforgettable. Lauren's mom had early onset Alzheimer's disease. And so when she met and started dating Seth, her mother was just at the point of getting diagnosed at, I think, 54 years old. So it's a really terrific short 37-minute documentary a lot of people relate to. So we're really excited about that

Rich Towne:
And that's fantastic. I'm sure most of the viewers of this show will definitely go back and watch the documentary that we've just talked about, especially with this disease because it's so relatable.

Alzheimer's disease is a progressive terminal brain disorder with no known cause or cure, for those on the show that might not be as familiar with it. As the most common form of dementia, Alzheimer's has an estimated impact of 6.5 million Americans above the age of 65, and rates are expected to triple by 2050.

The disease slowly erodes the mind of an individual resulting in confusion, memory loss, cognitive problems, and the eventual inability to communicate or care for oneself. Among all US age groups, Alzheimer's disease is the seventh leading cause of death. Research is still trying to uncover the root cause of Alzheimer's disease. But individuals do experience an increased risk as they age, and it tends to run in families.

Once an individual is diagnosed, medications are available to slow down the progression of cognitive symptoms. However, these medications are not a good option for everyone, and research is vital to discovering better treatments and potential cures for Alzheimer's and all types of dementia.

For the past 50 years, the BrightFocus Foundation has funded worldwide research to defeat Alzheimer's disease, glaucoma, and macular degeneration, in addition to providing resources and support to patients and their loved ones. Their outreach includes BrightFocus Chats, virtual community groups, Alzheimer's expert Q&A sessions, special events, and multilingual education programs to raise awareness about brain health.

Today, we're so excited to chat with Nancy about our work at BrightFocus with a special focus on recent research breakthroughs. And like I just mentioned, BrightFocus is celebrating its 50th anniversary. So congratulations on that. And over that time, the organization has invested nearly 290 million towards Alzheimer's research. Can you talk a bit about the developments you've seen over the past half century and what you might be excited about in the years to come?

Nancy Lynn:
Yes, absolutely. Thank you. Yeah. We were founded in 1973 as AHAF, American Health Assistance Foundation, and at that time did a lot of things. And the foundation was actually instrumental in the development of the first artificial heart back in the day. But we ended up coalescing around Alzheimer's disease, macular degeneration, and glaucoma. And actually of the 290 million that we've invested in global research worldwide over those years, about 175 million of that is on Alzheimer's and the rest on the vision-related diseases.

And one of the unique things the foundation does is look at the eye-brain connection. And in fact, we convene a satellite conference ahead of the Alzheimer's Disease/Parkinson's Disease Conference that is on the common features of neurodegeneration. So the eye is actually connected to the brain by the optic nerve. So it's really interesting.

And when we're talking about more recent breakthroughs, there is a lot of work going on focused on diagnosing Alzheimer's by looking into the eye, looking at blood vessels in the eye. And it's a really exciting area, learning a lot more about cognition through the eye.

But over the course of those many years, because we fund what we call investigator initiated grants where someone proposes a novel idea to us, and we want to be able to allow an emerging researcher to show proof of concept again all over the globe, we've been involved in a lot of breakthroughs, and I would encourage anybody who's interested in looking at this to go to our site for our 50th anniversary, which is, where we have a timeline exactly as you're talking about, of sort of critical breakthroughs.

But some of them we've seen, especially in the last five to 10 years, incredible advances in gene editing technologies, new and first ever kinds of glaucoma and macular degeneration treatments and diagnostics in 2016 was the first creation and treatment of retinal ganglion cells using adult skin cells. There are just dozens and dozens of these kinds of things.

In 2017, we created an international brain bank for Down syndrome, so researchers can use tissue. We've done some groundbreaking sleep studies that show sleep protects against Alzheimer's. A lot of projects, as I mentioned, focusing on detecting Alzheimer's through the eye and a lot that are discovering new biomarkers, new indicators of different types of dementias.

And, of course, this year has been quite seminal because we've had the first approval of a disease-modifying therapy for Alzheimer's ever. And a lot of the research that we've funded over the years has led to the development of these now monoclonal antibody therapies that hopefully will actually slow down the progression of the disease.

Rich Towne:
So that's very interesting. I think the first thing that I'm thinking about is just the diagnosis of Alzheimer's at large what goes into the diagnosis? What are some challenges around the diagnosis? And because I find it very interesting, if it's available into that diagnosis through the eye, what kind of test would that be?

Nancy Lynn:
So before a year or two ago, Alzheimer's could only be detected on autopsy. There's no way to definitively diagnose Alzheimer's as opposed to other forms of dementia, which there are many. And then a PET scan was developed called Amyvid, which was bought by Eli Lilly and Company. But that PET scan is expensive. It only can be given at certain major institutions, and it's not reimbursed.

So there's some of the problems. You said, "What are some of the problems?" It's not easily accessible, it's not affordable, and there's a very short half-life of the tracer in it. So it can be used for clinical trials now primarily, but it's not the kind of thing where you can detect in the public.

So then, there's what we would call your typical memory screening tests that go from pencil and paper to now a lot of computerized detection types of things that measure different things. But the big, big, big breakthrough this year was blood tests, the ability to detect Alzheimer's biomarkers, amyloid and tau are two different types of proteins in the blood. And the really groundbreaking test called Precivity has been launched by a company called C2N Diagnostics, of which BrightFocus was one of the critical early funders, so we consider along with others a feather in our cap.

But that's really exciting because a blood test clearly is cheaper, quicker and more broadly available than a PET scan or a cerebrospinal fluid tap, which was the other way to find those proteins. So that's exciting.

And then, there's a lot of different technologies now, companies launching technologies that look into the eye, and they can detect again. Some will look at differences in blood vessels. You can actually see that amyloid protein in the eye. And in the horizon, a lot of folks doing studies on linguistics and now with AI, everything's on the table. But I've heard at some point, you'll be able to diagnose Alzheimer's years and years before symptoms appear just by changes, very subtle changes in language. So it's a very exciting time.

Rich Towne:
It definitely sounds like an exciting time. And I think one of the things for anyone listening that has maybe a loved one or maybe for themselves is concerned that they might either be at risk for Alzheimer's or have started to develop symptoms. What's the usual route that those patients would go through to get that diagnosis? Is that a primary care provider? Would they see a specialist physician?

Nancy Lynn:
So this is a real problem, to be honest, because until this year there were no disease-modifying drugs available, there were just some symptomatic agents which are Aricept and Namenda primarily, a lot of doctors were resistant to trying to diagnose Alzheimer's or other dementias because it takes a lot of time, is one issue, and it's not necessarily reimbursable for a primary care physician. And they feel like there's nothing we could do.

So if you bring your loved ones in and you say, "I think something's changing, they're repeating themselves," some of them will say, "Well, come back in a year." At this point, that's the worst thing you can do because the new treatments that are coming to market can only slow down the progression if they are used very early in the disease state. And there are ongoing trials now looking at whether those drugs could slow down progression before any symptoms appear. So the earlier you know, the better.

So you should go to a primary care physician, tell them you have memory concerns and seek a screening exam. There are a lot of other paths because there may be resistance or just a lack of knowledge by that primary care physician. And I would again encourage folks to visit our website, or has a lot of resources for how to try to get diagnosed.

But what would normally happen if a primary care physician or a local memory center, if you can find one, gives you a pencil and paper screening test or some kind of simple screening test, they will have a numbers rating scale. And if that number rating gives cause for concern, they would refer you to a neurologist or a neuropsychologist to get a more definitive diagnosis, go for more testing, and get a more definitive diagnosis because I've talked about different types of dementia.

There could be frontotemporal dementia, Parkinsonian dementia, Lewy body dementia, alcohol-related dementia. And also, symptoms of dementia could be from something else entirely, infection in the brain or blood microbleeds.

So the problem, again, another huge problem in diagnosis and detection is that there are not enough neurologists in the country and the wait time to see a neurologist, if you can even find one that is capable of doing these diagnoses can be six to nine months. So all of these are problematic. And a lot of us in the advocacy space are trying to develop tools and shortcuts in ways that people can get some of those screenings and get earlier detection.

There's also companies with technologies like Cogniview or Cogstate or Linus. There are a lot that are coming out with machines that are not expensive to do and trying to get them into doctor's offices, get them into pharmacies. I mean, the ideal thing would it be if you could go to your CVS or your Walmart and say, "I'd like a memory exam," and you start early, get a baseline because the most important thing is to see is it changing over time?

There's also a wonderful tool that a colleague of mine, Brooks Kenny, helped to develop.I think it's Brain Guide where you can actually do a telephone call, and it's administered by bots. So no one's actually getting your private information or you don't have to talk to anybody directly, but it will give you a very short phone test that can also, again, give you an indication of whether there is concern or not. It's not a diagnostic tool in and of itself, but that's a great way for people who don't have access, even internet access necessarily can just do it by phone. And we could actually provide Antidote with our list of resources for getting screened and diagnosed and would be very happy to share that.

Rich Towne:
And that would be fantastic because I think those tools are especially lacking. So I think really now that there's a lot of buzz, like you mentioned about these newly approved therapies, but as you said, there's a very specific timeframe that they can be used in. Just for the reference to the audience, how narrow is that timeframe?

Nancy Lynn:
Well, that's really hard to say because it's depending on what type of dementia we're talking about, because there are early onset forms of dementia, as I was talking about with Lauren Miller Rogen's mom. Down syndrome patients can get Alzheimer's disease very, very early.

But if we're going to generalize, really generalize, the early onset form most typically presents when you're in your 60s. And what we would call late onset or regular onset, a lot of confusion in the terminology in Alzheimer's, would usually present in your 70s. And so in terms of the specificity of the window that I was referring to, it would be particularly for the new drug that was approved this year, Leqembi and potentially another drug that we expect to be approved in 2024 called donanemab that are those monoclonal antibodies.

They need to be used when you're at the mild or what they call mild cognitive impairment or early Alzheimer's disease stage. You can't have progressed too far to moderate or advanced Alzheimer's. So that window, again, it could be in your 60s. It could be in your 70s. It could be in your 50s. We're not exactly sure yet.

There is the ability to get a reimbursed memory screen from a primary care physician once you turn 65 at your annual wellness visit. Unfortunately, there's not a lot of uptake in that, but that is a covered procedure. And so, if you ask your doctor, if you go in once you're 65 and say, "I'd like my annual wellness visit, and I'd like to have a memory screening as part of that," they should be able to provide that to you and get reimbursed for it. So that is something everybody should ask for if they can. But if you're in your 50s and you're concerned about yourself or a loved one, then, you would want to go in as soon as you're noticing something that's really problematic.

Rich Towne:
And that's also just fascinating because when a resource like that is available, to hear that it has low uptake is shocking. And one of the things in your answer is we have the drugs to treat this admittedly very narrow swab of the population. But obviously, there's so many different areas of need, whether it's severe patients, patients who haven't shown any impairment yet and everything in the middle of very unique cases, which is where clinical trials come in.

So one of the focuses we have on that podcast is despite this huge, huge need for these therapies to make it to the market and hopefully get approved by the Food and Drug Administration in the United States, there are a ton of challenges that lie in wait for these trials. And specifically for the Alzheimer's space, is there anything in particular that really stands out to you as key obstacles or challenges for both patients, investigators, and sponsors?

Nancy Lynn:
There are many, as I'm sure you're aware or might expect. In particular, my team has been focusing quite a lot on brain health equity issues and the absolute need for diversity, for greater diversity in clinical trials. And so, that's a real passion spot for me for many reasons, including that at the very tail end of 2022, legislation was introduced that demands that clinical trial sponsors include a diversity plan in their trial outline.

And so, it's a little bit unclear right now what that means. What does a diversity plan consist of and how is it reinforced?

And so that means recruiting a lot of people, but it also means recruiting a diverse enough population so that you know drug is going to work in that population because not just for reasons of social justice that we want people of every color and every background to be able to have access to treatments, but that treatments work differently in people of different ancestries.

And so there's a lot of discussion about the use of the terms race, ethnicity and ancestry because there's been a longstanding rule that there's no biological race and ethnicity difference. But when you're talking about ancestry, you're talking about genetics. And then there are differences.

And so let me use the Leqembi trial that ASI ran as an example. This is the drug that is now approved. And I did want to mention there was one other drug approval this year that was critical, and that was a drug that Otsuka has for agitation. It had already been approved for Parkinson's-related agitation. It has now been approved for Alzheimer's-related agitation, which is great. But in the Leqembi trial phase 3 trial, there were the best efforts to date so far made to include Hispanic participants and Black American participants.

And at the end of the day in the trial, they were able to recruit, I believe, it's about 22 or 23% Hispanic participants, which is fantastic. And they made a concerted effort to do this, but they only had four and a half percent black American participation. And I actually got a chance to speak directly with their statisticians about this because the media was putting a very negative spin, and this is an area I'm very interested in.

And they said that the reason why the percentage was lower for that community was not because they actually recruited fewer participants, but because there was a higher, what we call screen fail rate. There was a higher rate of them not meeting the entry criteria. And I assumed when I was speaking to them then that was because of what we call comorbidities, that they might have too much high blood pressure or diabetes or other types of things that would disqualify them.

And they said "No." Where they were not meeting the criteria is that they didn't have enough of the high level of that amyloid protein in their blood. And that to me was shocking even after I'm in this field about 15 years day in and day out, because we often say that Alzheimer's occurs in two times at the rate in the Black population as in the Caucasian population.

But if we're saying it's Alzheimer's, the definition is that you have a certain level of amyloid in your brain. So this to me, rather than just a social justice question, is a really important scientific question because if you're having a population that's not presenting with as high an amyloid level as expected, that needs research. 

So the field has quickly turned and looked and is just starting to go down this route, which also is very exciting, but very frustrating to many. And I saw a presentation recently that looked at Puerto Rican Americans versus Mexican Americans and again, looking at these biomarkers in the blood, and there were big differences between Puerto Rican Americans and Mexican Americans.

So if the future is precision medicine and the future is AI and the future in Alzheimer's or dementias is that you want the right drug for the type of dementia that you have, scientifically to have appropriate knowledge, you have to have diverse populations. And there are many, many barriers that keep populations from participating.

Not the least of which is that we have 20-some odd, I think about 27 Alzheimer's disease research centers federally funded across the country at major academic institutions. So if you're near Emory or you're near a major institution, if you'd really try hard, you could get access to those trials, but the rest of the country cannot participate as easily. It is much harder for a lot of populations.

But I would say to your audience, whether they're professionals or just general public, if you have an interest in participating in a research study or a clinical trial, please call us because we will try to find a way for you to do so. It's just so critical for the field, and it's critical for everyone because you do get better care generally speaking when you're participating in research, and you do have more opportunities. And people tend to feel a lot less helpless and hopeless if they're involved in a research study where they feel that they're doing something for themselves but also for their kids and the next generations.

Rich Towne:
And that was just a great answer, and I think that went really into depth. I think that the biggest theme of clinical research going forward as we continue to learn about some of these differences that ancestry can cause, and especially boosting trust in patients who are going to receive the drug, knowing that it's been tested in people like that, it really, really helping to boost that uptake down the road.

But one of the things when you're talking about the reason that a lot of Black patients failed the inclusionary criteria was the low levels of amyloid protein. So I thought this would be an interesting point to switch to talking about those inclusionary and exclusionary criteria and how sponsor companies build them and maybe some of the challenges around. I know one of the biggest ones for Alzheimer's is having a study partner and maybe some of the other criteria with study visit schedules and, as you mentioned before, the lack of research centers nearby.

So if you could really touch on some of the challenges that have been encountered with the way that sponsors and investigators are building these protocols and their inclusionary-exclusionary criteria.

Nancy Lynn:
Yeah. I think in terms of trial design, inclusion and exclusion criteria are one of the issues and an important one. And I do believe that there a lot of the field is trying to address that to make participation a bit easier. But having a care partner with you in a study for Alzheimer's, it is critical given the nature of the disorder.

And it does make participation very difficult because it's very time-consuming. And again, I think we're back to one of the ways I see past that ultimately is the decentralized trials, they call. I'm going to use as an example of project that BrightFocus has been involved with for over two years now in rural South Georgia in a city called Valdosta, which is as south as you can go in Georgia and on the border with Florida. And this is a community that is 60% Black. And of the 60% that are Black, about 40% of those people make less than $10,000 a year.

It's still a very segregated type of community economically as well as otherwise. And so we've been working down there with a wonderful little organization called Reminiscent that's run by a woman named Dr. Debra Tann who lives in that community. And she was a college level educator whose husband got frontotemporal dementia. And when that happened because she had so much trouble finding treatments and diagnosis for him, she turned all of her professional teaching skills to dementia and has been trying to become a dementia teacher and pioneer in that community. And we have been working with her now.

So used that community as an example. There is no mass transportation, none. So if you're making under $10,000 a year and you can't use mass transport and the closest memory center to you is an hour and a half away in Albany, Georgia, and the closest clinical trial site you know of is at Emory, which is three and a half hours away and it takes you nine months to get an appointment with a neurologist if you could even get there, it's impossible.

So what we're trying to do there is to build a model, where you could bring more resources into the community, people who know how to do screens, memory screenings, people who would know that if you wanted to participate in a study, it's better in Tallahassee or Gainesville or Jacksonville or closer actually than Emory and that know where the nearest pet scan availability is.

And then we're working there with a clinical trial company called K2 Medical that have mobile vans who have offered to come up and bring mobile vans with memory screening units. And they have the ability then if somebody does screen and seems to be eligible based on their screenings for a trial, they can help provide all of the infrastructure, the Lyft rides, things that make it easier for the care partner to participate.

But it's obviously not simple, but we're working towards this year trying to open a little brain health center or a health screening center where we could offer some of the least invasive initial testing. And then, if people have red flags, we could end up like a hub and spoke model connecting them to all those resources, whether it's the Albany Memory Center or it's the local nursing program or it's a site in Gainesville or it's K2 Medical, CALA, and get people in these under-reached areas connected up to bigger health systems that have greater resources.

And the field is very eager to do this, but they want to find cheap fast ways to do this. And so far, I'm at the conclusion that maybe you can make it cheap, but fast is just not going to happen because you have decades and decades and decades of structural racism that have led to health inequities that just aren't easily.

It's going to take a lot of time and thoughtfulness and provision of resources and interest in listening to communities and listening to people who don't qualify for trials across the boards and saying, "What did they feel they need to be able to participate or to be more brain healthy." And that's I think one of the missing pieces.

One of the other missing pieces I wanted to talk about in terms of getting into clinical trials or sponsors should be aware of is I think there's a big underestimation of how important the bedside manner of the recruitment team is. People go to volunteer to be in a clinical trial, people of all races and backgrounds, and I think there's not enough focus on training staff in terms of their communications skills and compassion skills and humanism when they are screening people.

It's still a very stigmatized disorder. It's still a terrifying disorder. So when you go to volunteer for a clinical trial and you go through your battery of tests and then you're just told, "No, you don't qualify, you don't have amyloid," you can feel very upset and offended even though that's good news.

But people go back to their communities then and say, "I didn't qualify, and I spent my whole day, and I did this and I did that." So there are some wonderful examples of clinical trial companies now that do take this advice on board. I think sponsors need to take it. Clinical trial sponsors need to take that really deeply on board too and think about the language they use and how they talk with people and communicate with people over the course of time because this is going to be a really long haul. We need a lot of research participants over the next couple of decades.

Rich Towne:
And I think that that leads directly into one of the ways we like to end this podcast.if you had to give a single piece of advice, word of wisdom or suggestion to a patient, the patient population and their caregivers that are interested in enrolling in clinical trials, the actual study site staff and the investigator team, and then finally the people conducting the clinical trials, whether that's single site investigators or clinical trial sponsors, what would be, if you could get through to them, there's one piece of wisdom or suggestion that you think of. And this is obviously a big question, so feel free to think it through a little bit.

Nancy Lynn:
I actually haven't answered this question before, so it's a great question. And to be truthful, my gut just told me in terms of clinical trial staff would be something that probably sounds so trite, but pretend that person is your sister or your mom. And I'm sure that sounds so ridiculous, but I think it is so easily forgotten.

Remember, this is a human being and a human being who's terrified. And to me, that's the most important thing that you can do and try. If they don't qualify, don't send them away empty-handed. If you can't be in the position, which some are, to recommend a different trial, send them to a resource that can help.

Have them call Bright Focus Foundation. We will try to help them wherever they are in the country. I always also say that has a lot of resources that can be a little overwhelming and that's why I call us because they'll always be somebody who will answer the phone. And if we don't have the resource in-house, we'll refer you to.

And then there's area agencies on aging. There's a lot of resources out there if you find them. Tell the people to make that call or reach out to BrightFocus Foundation, and we'll give you a list of national resources to give to your patients. For the patient population, I would have to say don't stop trying to get answers.

Don't stop trying because it's really easy to quit to say, "Oh, the doctor won't see me. I don't know if I can afford the copay. I'm afraid to go, because if they prescribe a drug to me, I can't afford the prescription copay. I don't want anyone to know that I'm going to the memory doctor because they'll think there's something wrong with me, and I might lose my job."

There's so many things. And I don't want to bother my family. I don't want to be a burden to my kids. I'll just sweep it under the rug. Don't sweep it under the rug. Try to get a screening. You will be able to get it if you try. And so, that would be the single-most important. Don't give up. Try. Keep trying. There are so many of us out here who are passionate to help.

I don't think I had the sponsors, but for the sponsors really, I would say, please don't use jargon in your patient-facing communications. It is one of the worst mistakes. And a lot of sponsor companies will pay millions of dollars to marketing agencies to do brochures and the language fifth grade level, please, fifth grade level. You're communicating to all kinds of regular people. Don't try to impress your colleagues with the use of the appropriate terminology. Use terminology people can understand.

Rich Towne:
And I think that was all fantastic advice. It's been super insightful and if there's anyone listening that wants to know more, you've given a couple links and to call BrightFocus. But are there any specific places that you would send our listeners?

Nancy Lynn:
I would actually invite your listeners to email me directly. And my email is nlynn, N-L-Y-N-N And if it's not a question I can answer, I can reach a researcher, I can reach a clinical trialist, I can reach a healthcare system. So we will actually try to help. I invite you to email me personally. That's what we all have to do. It's hand-to-hand combat Alzheimer's disease. It is hand-to-hand combat, and we have to help each other.

Rich Towne:
All right. And hopefully, we have a lot of people that feel empowered and reach out to you, or even better, hopefully, they just feel encouraged to undergo the journey and just keep on trying, like you said. So once again, thank you so much for appearing on Talk of the Towne, Nancy. This was a fantastic discussion.

Nancy Lynn:
Absolutely, my pleasure. Thank you for having me.