Alzheimer’s disease is a heartbreaking diagnosis and tragically there is no cure. But every day, researchers, scientists and the medical community are working to change that. In this episode, we speak with three guests who are fighting to bend the trajectory of Alzheimer’s disease and, in doing so, offering hope for the millions suffering from this devastating illness.
Alzheimer’s disease is a heartbreaking diagnosis and tragically there is no cure. But every day, researchers, scientists and the medical community are working to change that. In this episode, we speak with three guests who are fighting to bend the trajectory of Alzheimer’s disease and, in doing so, offering hope for the millions suffering from this devastating illness.
Speaker 1 (00:06):
People need to know that Alzheimer's can happen to absolutely anyone just as cancer can.
Speaker 2 (00:11):
She's not remembering things. She's not remembering how to do things. She used to do all the checkbook on everything all the time. She couldn't do that anymore. She couldn't cook anymore, she couldn't do the checkbook anymore.
Speaker 3 (00:30):
He has a difficult time expressing himself as far as saying things, but the one thing that he doesn't struggle saying is how much he loves you.
Speaker 2 (00:41):
I think every once in a while, I want my old Fran back.
Dr. Michelle McMurry-Heath (00:51):
Alzheimer's disease is a heartbreaking diagnosis, both for patients and the loved ones surrounding them. The emotional cost for all involved is daunting and it robs families of time and memories. It's estimated that Alzheimer's total economic burden for the U.S. is well above $300 billion, and expected to reach $1 trillion as the population ages. Tragically, there is no cure, but every day researchers, scientists, and the medical community are working to change that. With the approval of a new drug and others in development, we are hopeful for a new dawn in Alzheimer's treatment.
Dr. Michelle McMurry-Heath (01:38):
Today, we talk to three guests working to change the trajectory of Alzheimer's disease. They offer hope for the million suffering from this devastating illness. I'm Dr. Michelle McMurry-Heath, and you are listening to, I AM BIO.
Dr. Michelle McMurry-Heath (02:13):
Our first guest is Dr. Maria Carrillo, the chief science officer of the Alzheimer's Association. Like so many of us, she has a personal connection to the disease and knows firsthand the demand it can place on a family.
Maria Carrillo (02:29):
My own mother-in-law and father-in-law both passed away from Alzheimer's and vascular dementia. We felt this ourselves, the incredible cost to us as a family to try to keep them home as long as possible with 24-hour care, especially the last five years was incredible. And it came out of the family and friend pocketbook, so to speak.
Dr. Michelle McMurry-Heath (02:47):
Dr. Carrillo's passion to push the envelope in Alzheimer's research comes not only from personal experience, but from her background as a neuroscientist and internationally respected Alzheimer's expert. She works tirelessly to secure increased funding from both public and private sources. We asked her why this disease is so hard to treat and cure.
Maria Carrillo (03:13):
That's one of the very first questions that comes up. I will tell you that there are a couple of answers to that. The first is that the brain is very complex, very complex, and very protected as it should be, because it essentially is the CPU of our entire existence. We need every single brain cell. And as we have seen from experience with diseases of the brain, we cannot actually go in, biopsy the brain, see what's happening because it is a very protected organ and because we need every single brain cell in there, because it holds the key to our memories. This is very complex disease.
Maria Carrillo (03:53):
10 years ago, we started with $450 million a year to go around to the entire country in comparison to four, five, and six billion dollars at the time for heart, HIV, and cancer. So you can imagine when you really only have a fraction of the dollars for all the Alzheimer's research going on in this country, you're not going to make progress.
Maria Carrillo (04:20):
Today, thanks to efforts of the Alzheimer's Association and the Alzheimer's Impact Movement, we are actually at $3.4 billion, a more commensurate amount to fund Alzheimer's research. This will be an impetus for accelerated progress. We just need to give that money a little time to actually work in labs across the country, but we will be experiencing breakthroughs just like other diseases have, and hopefully start to experience a reduction in death rate from Alzheimer's and other dementia. Again, the way heart, cancers, and HIV have done as well.
Dr. Michelle McMurry-Heath (04:59):
More research funding is welcome news. As breakthroughs occur however, it's important that patients have equal access to them. Dr. Carrillo stressed that her highest priority is to eliminate barriers and ensure new treatments are available to all patients as soon as possible.
Maria Carrillo (05:19):
I think we all know and understand that Alzheimer's disease is a fatal disease with no survivors. So eliminating barriers to access of treatments as soon as they come online is our highest priority. And so right now, what we are working very hard on is to ensure access to necessary diagnostic tests like Amyloid PET scans and others, and newly FDA-approved drugs, including those that are approved through accelerated pathways, the way we have one certainly already approved today with several on the horizon.
Maria Carrillo (05:51):
The purpose of an FDA accelerated pathway is to allow for an earlier approval of drugs that can be used to treat serious illnesses with a critical unmet need, and Alzheimer's qualifies for that. It is a sign of hope for all of our families, because there are more to come. And again, we are focused on trying to do everything in our power to ensure access to these diagnostics and newly FDA-approved drugs as they come online.
Dr. Michelle McMurry-Heath (06:25):
An important point to make is that the access burden and incidents rate of Alzheimer's is not evenly spread. African Americans and Hispanics are at a higher risk than white Americans for contracting the disease, and they are often diagnosed in its later stages.
Maria Carrillo (06:45):
Differences do exist in ethnic differences as well. Older African Americans, for example, are almost twice as likely to have dementia than older non-Hispanic whites. Older Hispanic or Latin Americans are one and a half times more likely to have dementia than older non-Hispanic white. The scientific community is still trying to understand the reasons behind this.
Maria Carrillo (07:04):
In a survey we did associated also with our annual facts and figures report in 2021 in fact, we actually looked at one of the potential reasons why there is a reticence to actually even access care. And we found that discrimination was a huge barrier to dementia care. And that included of course, awareness, concern, and stigma about Alzheimer's that varied widely across different racial and ethnic groups. People from underrepresented groups want healthcare providers who would really understand their unique problems, their unique experiences. If we're going to, for example, give people advice on reducing their risk that involves diet, that diet should be reflective of that ethnic or racial group.
Dr. Michelle McMurry-Heath (07:52):
As we've talked about on previous I AM BIO episodes, the history of our healthcare system has often left black and brown around communities skeptical that they will benefit from efforts to improve representation and increase access.
Maria Carrillo (08:07):
And many black Americans distrust, I think research and clinical trials. And so ultimately, we need more representation within the clinical trial construct. But if we don't have people actually accessing healthcare, they're never really going to even be referred to clinical trials.
Maria Carrillo (08:25):
So we've got just a lot happening right now in our space in trying to understand sort of the reasons why underrepresented populations have an increased risk. But the last thing I'll say about that is that it's important to recognize that these populations also are in an increased risk for heart disease, and we've known that for actually decades. The issues around that are complex. Some of them could be genetic, some of them could be really social determinants of health and how people are able to access not only healthy foods, but healthy spaces to exercise and even again, accessing healthcare. And so those are complicated things that can overlay the genetic predispositions and biology. All of that is being studied now and will be very important to really understand in the years to come so that we can reduce risk for everyone.
Dr. Michelle McMurry-Heath (09:18):
When we come back from a break, we'll meet two biotech companies with innovative and disruptive approaches to addressing Alzheimer's disease.
Dr. Michelle McMurry-Heath (09:36):
It's not too late to register for the BIO International Convention. The world's largest biotech partnering event and gathering will be held in person from June 13th through the 16th in San Diego, California. Big breakthroughs happen when collaboration and innovation collides, so join us for four exciting days of networking, programming, and partnering that will shape the future of the biotech industry and our society. Visit bio.org/convention.
Nolan Townsend (10:22):
So our view is that in order to address the totality of Alzheimer's disease, we need to go upstream and look at the genetics of the disease, which we believe will help us to understand the totality of Alzheimer's disease.
Dr. Michelle McMurry-Heath (10:35):
This is Nolan Townsend.
Nolan Townsend (10:37):
I'm Nolan Townsend, CEO of Lexeo Therapeutics. We're a New York-based gene therapy company.
Dr. Michelle McMurry-Heath (10:45):
Lexeo is in early stage clinical trials to test a gene therapy for Alzheimer's. It's an exciting approach with enormous potential to stop or slow the disease, as Nolan and explains.
Nolan Townsend (10:58):
The challenge of Alzheimer's is that the view of some is that there is not a single pathogenic mechanism that's involved in the onset of Alzheimer's disease, that there are potentially multiple pathogenic mechanisms that are involved. And this may be amyloid beta, amyloid plaques, tau tangles, inflammation, and potentially other mechanisms that are involved. But the current approaches that are in development and even the currently approved approach to treat Alzheimer's disease are typically focused on a single pathogenic mechanism. These are either amyloid treatments, or they're tau treatments, or they're treatments focused on inflammation. So therefore they may not be treating the totality of the disease.
Nolan Townsend (11:40):
So our approach is to go upstream and treat the genetics of Alzheimer's disease, which we expect to have a downstream impact on multiple different pathogenic mechanisms. And I think what we've understood now with the advances in genetic medicine is that oftentimes genetics does play a major role in the onset of the disease, and that by treating the genetics of the disease, you can potentially treat the totality of a disease over the long term.
Dr. Michelle McMurry-Heath (12:05):
Nolan described how genetics may predispose an individual to Alzheimer's.
Nolan Townsend (12:11):
APOE4 homozygotes have the highest likelihood of developing the disease. So the existence of two alleles of APOE4, the APOE4 gene is what makes you an APOE4 homozygote. So the approach we're taking, we are treating APOE4 homozygotes. These are patients that have two alleles of the APOE4 gene. And these patients will have a 15 to 20 times higher likelihood of developing Alzheimer's disease. But patients that naturally have an APOE2 allele alongside APOE4, so one APOE4, one APOE2 have a normal risk of developing Alzheimer's disease.
Nolan Townsend (12:49):
So our gene therapy approach is fundamentally based on that genetic framework let's say, where we're actually adding the APOE2 gene to the central nervous system of APOE4 homozygotes, thereby seeking to alter their central nervous system to become closer to the APOE24 heterozygote profile that confers a normal risk of developing the disease. So if this were to work in a perfect form let's say, we would take a patient with a 15 to 20 times higher risk of developing Alzheimer's disease back to a normal risk of developing the disease. But the way we're thinking about it is not as only a risk reduction approach, we're actually using APOE2 as a therapeutic. That by adding the E2 gene, we believe this should stop or slow many of the pathogenic processes that are currently associated with Alzheimer's disease.
Dr. Michelle McMurry-Heath (13:49):
A significant benefit of gene therapy is its one and done application. Whereas most treatments require repeated therapies over the course of perhaps a lifetime, gene therapy would entail a single administration for the desired outcome.
Nolan Townsend (14:06):
We feel at Lexeo that the work we're doing is hopefully what society has always wanted from the biopharmaceutical industry, that there is a very difficult disease like Alzheimer's disease, devastating to families and we're developing a therapy that we hope to be a functional cure to the disease. A single administration therapy via an outpatient procedure that the patient only needs to be treated with once.
Nolan Townsend (14:33):
And so from our perspective, and hopefully society feels this way, this is sort of an ideal treatment, a mechanism for a difficult disease, such as Alzheimer's. And hopefully over time, not only does it alleviate the burden of the significant disease, but it also reduces cost for the healthcare system as well. So we hope that this is what everyone wants from us, and we also hope that we're successful in our work to develop therapy of this profile.
Mei Mei Hu (15:13):
My name is Mei Mei Hu. I'm the CEO of Vaxxinity.
Dr. Michelle McMurry-Heath (15:16):
Now we turn to a company with a completely different approach. Mei Mei and her company recognize two things, the cruelty of the disease and that it starts well before symptoms develop.
Mei Mei Hu (15:29):
There's a typical progression from early to late Alzheimer's, but it really affects each person in different ways. But generally, early Alzheimer's is when you have trouble remembering names. As it get more moderate, there's personality shifts, confusion, sleep patterns. And then unfortunately, late stage Alzheimer's is where you even forget functional things like walking, sitting, and eventually swallowing. So it's, unfortunately, a death sentence.
Mei Mei Hu (16:01):
Alzheimer's is an invisible disease until it's not, and that's why it's so difficult to treat. These toxic proteins, these pathology, they start decades before symptoms occur. Think about if you're living in a house and every year your foundation is being eaten up, but no one's checking and you have no idea until your house collapses. And by then, it's too late. That's Alzheimer's.
Dr. Michelle McMurry-Heath (16:22):
As you may have guessed from the name of the company, Vaxxinity is developing an Alzheimer's vaccine. Mei Mei explains how it would work.
Mei Mei Hu (16:30):
Our vaccine that's in the clinic right now targets these toxic amyloid proteins. That's the initial insult, that's the beginning of the cascade at Alzheimer's. And by intervening at that stage, we prevent the further destruction of additional neurons by these toxic proteins. And when you halt that, unfortunately, we don't expect to be able to reverse it, but we can do is you can slow the progression of it. So instead of getting worse by X, you're slowing that progression by 50%. And by slowing by 50%, you can extend a patient's quality of life by years. Because remember, this is a slow disease. It takes years and years to evolve. So every little bit that you slow by 50% or 30%, you're extending life by years.
Dr. Michelle McMurry-Heath (17:21):
Vaxxinity is preparing to conduct a large scale clinical trial that will test the efficacy of their approach.
Mei Mei Hu (17:29):
We've conducted multiple clinical trials in Alzheimer's patients. Our latest one was in early Alzheimer's patients. And what we're looking now is to run a large scale efficacy study to kind of confirm the findings that we saw in our smaller trial. So in our phase 2A, what we saw was a slowing of disease progression by about 50% in multiple cognitive tests. So we also saw positive trends in biomarker readouts. So that means both in actual measure of amyloid and the brain and also functional MRI. So what's the activity of your synaptic nerves. So we saw positive trends in dose dependent manners across all of our endpoints. And that's what encourages us to go into a larger scale study.
Dr. Michelle McMurry-Heath (18:18):
If Vaxxinity's technology works, Mei Mei believes it will be a game changer.
Mei Mei Hu (18:26):
We see vaccines against chronic disease, in Alzheimer's particular, as part of the third biologic revolution. So the first biologic revolution was vaccines, generally speaking, against polio, against COVID, against infectious diseases. That prolific medicine has helped us expand our lifespan by over double, over the last 100 years.
Mei Mei Hu (18:47):
The second biologic revolution are these beautiful monoclonal antibodies or protein drugs. And these have been unbelievably effective, almost like a miracle drug against lots of chronic diseases. But the problem is they're very expensive, difficult to take. And as a result, serve less than 1% of the world's population. What we're doing is bringing the efficiency of vaccines. So they're cheaper, they're more convenient, they can be produced at scale, and bringing them to chronic diseases. And that's why we believe that more people can get access. This is what we call expansive disruption, where you're not taking market share, but you're actually expanding the market to all those in needs and allowing us to expand from 1% of the population to everyone who needs it.
Dr. Michelle McMurry-Heath (19:31):
Greater access to life-saving drugs is what drives Mei Mei and her team. She likes to refer to their approach as the democratization of health.
Mei Mei Hu (19:40):
Our mission at Vaxxinity is to democratize health. That means delivering transformative medicines that are cheaper, more convenient, and more accessible to all patients. We believe that diseases don't discriminate and neither should medicine. So we're committed to delivering more health for more people.
Dr. Michelle McMurry-Heath (19:55):
That's a goal we all share, especially for a cruel and devastating disease like Alzheimer's. It has confounded the biopharmaceutical industry for a long time, and we are so grateful to the perseverance and innovation of these biotech companies as well partners like the Alzheimer's Association that refuse to give up.
Dr. Michelle McMurry-Heath (20:19):
Make sure to subscribe, rate, and/or review this podcast and follow us on Twitter, Facebook, and LinkedIn at I Am Biotech, and subscribe to Good Day BIO at bio.org/goodday.
Dr. Michelle McMurry-Heath (20:34):
This episode was developed by executive producer, Theresa Brady and producers Connor McCoy and Marilyn Sawyer. Sound design and mixing by Jay Goodman. Theme music created by Luke Smith and Sam Brady.