A New Drug to Tackle Alzheimer’s
While cancer and heart disease are the two leading causes of death in the United States they’re no longer the death sentences they once were — thanks to advances in medicine. The same cannot yet be said for Alzheimer’s disease, which affects over 5 million people in the United States.
But a new drug has researchers hopeful that there may soon be a way to treat the declines in memory, thinking, and reasoning associated with Alzheimer’s. Results from the Phase 1b safety trial of Aducanumab, developed by the pharmaceutical giant Biogen, were recently published in Nature. The data suggest that Aducanumab is removing amyloid plaques — thought to contribute to cognitive decline — in the brains of patients with early Alzheimer’s.
Aducanumab is now in Phase 3 efficacy trials, where researchers hope that the drug will demonstrate a positive impact on cognition. Heather Snyder, senior director of medical and scientific operations at the Alzheimer’s Association, says that the drug is the result of a years-long line of inquiry.
“The clumping of the beta amyloid is one of the hallmark brain changes we see in Alzheimer’s disease,” Snyder says. “Targeting that particular hallmark has been really a focus of the field for the last 15 years or so.”
And along with advances in drug research targeting amyloid plaques, technology is making them easier to study. As our best-protected organ, the living brain has long evaded easy observation. But in the Aducanumab study, Snyder says researchers used PET imaging to measure beta amyloid levels in living individuals — a tool that that more and more clinical studies are making use of.
“They were able to take a picture of the brain and see that [individuals] had elevated beta amyloid and then test a drug targeting beta amyloid,” Snyder says. “We know that actually historically, over the last 15 years or so … before this technology was available, about 20 percent of individuals that were in these clinical trials targeting beta amyloid did not actually have elevated beta amyloid. So the drug was targeting something that wasn’t there.”
The two ongoing Phase 3 trials of Aducanumab are monitoring approximately 2,700 patients worldwide for evidence of the drug’s impact on cognition and disease biology.
But while Aducanumab researchers could finally have the measurement tools and the drug to zap amyloid plaques, Snyder admits that a successful Phase 3 trial might not provide all the answers we need to cure Alzheimer’s. New studies are targeting a protein called tau, which also builds up inside the brain cells of Alzheimer’s patients in structures called tangles. Scientists are still aren’t certain that targeting either buildup will impact the cognition of Alzheimer’s patients, but Snyder sees progress on both fronts as being important to the development of a treatment.
“Think about heart disease,” Snyder says. “It’s a complex disease and there’s not really one shoe [that] fits all. Depending on where you are in the disease progression, depending on the biological changes that you may have, depending on some other aspects of your own medical history, the treatment that your health care provider might suggest could be lifestyle, it could be medication. It could be a combination of medications with lifestyle. And that’s really where the field in Alzheimer’s is moving, is this idea of a potential combination. How can we put either medication and lifestyle or medication and medication together to best combat this disease?”
Ultimately, Snyder adds, Alzheimer’s researchers want to identify those at greatest risk for Alzheimer’s, and intervene with treatment at the earliest possible point — not unlike we can with heart disease and some cancers. And given how far the research has come in recent decades, Snyder is optimistic that we may not be far away from preventive Alzheimer’s care.
“When we compare Alzheimer’s disease to other complex diseases like cancer or heart disease, we’ve been investigating those for decades, for centuries, in some cases,” Snyder says. “When we think about Alzheimer’s, in fact it’s about a 35-year-old field. Really, in terms of about 90 to 95 percent of what we understand about the disease has [come] in the last 35 years.”
Heather Snyder is Senior Director of Medical and Scientific Operations at the Alzheimer’s Association in Chicago, Illinois.
JOHN DANKOSKY: This is Science Friday. I’m John Dankosky. Ira Flatow is away. Cancer and heart disease may be the two leading causes of death in the US, but thanks to advancements in medical science there are treatments available. Many people do recover from what at one time was considered a fatal diagnosis.
That is not the case however for Alzheimer’s disease. For the 5 million people in the US with Alzheimer’s, there’s very little that can be done right now to slow the progression of cognitive decline that’s the hallmark of the disease. The most promising treatment– a drug called Aducanumab– is still undergoing clinical trials, but results published this week are giving the medical community a reason for hope. The drug appears to be removing the amyloid plaques from the brain, which are thought to contribute to the symptoms of Alzheimer’s.
My next guest is here to talk about how hopeful we should really be. Dr. Heather Snyder is Senior Director of Medical and Scientific Operations at the Alzheimer’s Association. Welcome to Science Friday.
DR. HEATHER SNYDER: Thank you so much for having me.
JOHN DANKOSKY: And if you’ve got a question about treatments for Alzheimer’s, you can call us at 844-724-8255. So, first of all doctor, this drug has been in development for a while now. Can you give me a sense of the testing this drug has gone through so far?
DR. HEATHER SNYDER: Absolutely. So this drug actually was– or this experimental drug was developed from a European company and entered into a Phase 1 clinical trials– or really the safety– testing the safety in 2012. But it really comes from about the last 15 years of work in the field where we’ve both seen an explosion of the idea of being able to target the beta amyloid– one of the hallmark brain changes– the aggregation, the clumping of the beta amyloid is one of the hallmark brain changes we see in Alzheimer’s disease.
And so targeting that particular hallmark has been really a focus of the field for the last 15 years or so. Really starting with the idea of active immunization– meaning that you’re making the antibodies inside the individual. And then the field’s focused now more on the idea of passive immunization. So developing the antibodies outside of the body and then infusing them into the individual as a potential way of lowering the beta amyloid. And the thought is that if we lower the beta amyloid, are we able to impact the cognition– the thinking, memory, and reasoning that we know changes in Alzheimer’s disease?
JOHN DANKOSKY: So tell us more about the data that you have from this first study– the first phase of this.
DR. HEATHER SNYDER: So this is the Phase 1 reports out from the company of their clinical trial. Again, it’s testing the safety. It was about 165 individuals and these trials– this trial launched in 2012. And they started reporting results out– the top line results in December of 2014, and then some of the more specific results in March of 2015 at the Alzheimer’s Association International Conference last July. And now we’re seeing this– the culmination of all of their results where they tested four different doses of this particular experimental drug. And they’re reporting out their Phase 3.
The company has actually moved into their Phase 1. They’ve actually moved into Phase 3 trials. They announced that based on their preliminary findings, where they both see– they see an impact, or potential impact, of this drug on the participants– that they’ve moved into a Phase 3, which is really testing the efficacy. So are they able to impact both cognition as well as the underlying biology of the disease with this drug? And those two trials are ongoing right now and recruiting– actively recruiting volunteers.
JOHN DANKOSKY: And again, volunteers and people who are part of this trial who are in the very early stages of Alzheimer’s.
DR. HEATHER SNYDER: That is correct. And actually one of the really unique things about this trial when it reported out in 2015 was the fact that this study used a tool called PET imaging– beta amyloid PET imaging– to detect the levels of beta amyloid in living individuals. They were able to take a picture of the brain and see that they had elevated beta amyloid, and then tested a drug targeting beta amyloid.
We know that actually historically over the last 15 years or so that about 20%– before this technology was available that about 20% of individuals that were in these clinical trials targeting beta amyloid did not actually have elevated beta amyloid. So the drug was targeting something that wasn’t there in those clinical trials. And so that’s really unique in this particular study. And we know that there are other ongoing clinical trials that are using a similar tool– a similar tool or a similar way of confirming as they enter– they enroll people in their clinical studies to confirm that they have the underlying biological change that they’re targeting.
JOHN DANKOSKY: So of course this biological change is the target of this drug and other research. The question is, we don’t know for sure that the amyloid build up is exactly the thing that we need to be taking care of. It’s one of the theories that’s out there. Can you talk about that a little bit? About how sure we are right now that amyloid beta is the biggest problem to solve in trying to find a cure for Alzheimer’s?
DR. HEATHER SNYDER: Absolutely, and great point. And when we think about Alzheimer’s disease, we actually define it by two hallmark brain changes. One is the build up of the beta amyloid. And the other is the build up of a protein called tau, which accumulates inside the brain cells in something we call tangles.
We’ve seen an emergence of studies that have been targeting the beta amyloid, but there’s also new studies that are entering into clinical trials targeting the tau protein. We don’t absolutely know that if we target beta amyloid and lower it, are we able to impact memory, thinking, and reasoning? That’s still an idea that the scientific community is testing. We also don’t know if that’s going to be the case for tau. And if you target the tau protein, are you able to impact thinking, memory, and reasoning for the individual?
There’s really two other ways that the field is going. One is looking beyond beta amyloid and tau, and thinking about, for instance, the immune system, thinking about the metabolism pathways of the brain. And we’ve seen in the last three to four years, really, an emergence of clinical trials entering into Phase 1 and Phase 2. Really testing the safety and the tolerability and the dose of potential drugs that are targeting those pathways.
And in the last couple years we’ve actually seen an increasing in our understanding that this is an incredibly complex disease. And the likelihood that it’s going to be one drug, one target is probably more going to be a combination of things. Whether it’s a combination of drugs or a combination of drug and lifestyle– think about heart disease. It’s a complex disease and there’s not really one shoe fits all. That depending on where you are in the disease progression, depending on the biological changes that you may have, depending on some other aspects, other components of your own medical history, the treatment that your health care provider might suggest– it could be lifestyle. It could be medication. It could be a combination of medications with lifestyle.
And that’s really where the field in Alzheimer’s is moving. Is this idea of potential combination. How can we put either medication and lifestyle, or medication and medication together to best combat this disease?
JOHN DANKOSKY: And is this progressing in the way that medical science progressed when we were trying to tackle the problem of heart disease? Or as we continue to tackle the problem of cancer? Is Alzheimer’s that much more complex in the way we need to understand it in order to attack the disease?
DR. HEATHER SNYDER: I’m not sure it in of itself is more complex, but the brain is complex. And the brain is protected. We have a barrier that protects anything coming from outside of our brains into the region where our brain is called our blood-brain barrier. And so it’s a tightly regulated and tightly protected organ that we have, and so you can’t really just open up and take a look inside a living person to see the changes that might be happening in different people over time.
And so developing technologies and ways to do that in a living individual has been an area that we’ve really seemed to explore. So in the last– similarly in the last 15 years we’ve really seen that those changes developing in the field in terms of the technology to be able to make those– to detect the underlying biology in living individuals.
JOHN DANKOSKY: When we report on something like this that is promising– another promising finding, what are the things that someone in your position needs to caution us about? I mean what are the things that we still need to be concerned about when we see something that looks promising for something that’s so deadly?
DR. HEATHER SNYDER: So this is a Phase 1 trial. So this is really the early stages of a clinical trial– testing the safety. Although they saw hints of potential benefit on the memory, the thinking, and the reasoning– as well as the underlying biology in terms of lowering the presence of the beta amyloid plaques based on the PET imaging in this particular study– they’ve actually moved it into what we really need to see– replication of these results. And that’s the Phase 3 trials. And there are two ongoing Phase 3 trials that have over 1,300 people in each of them. So over about 2,700 people total from around the world. Where I think when we need to see the results in a larger and diverse population and determine, are they are they able to be replicated?
JOHN DANKOSKY: What are some other promising treatments that are out there? What are some things that are exciting you right now in this field?
DR. HEATHER SNYDER: It is an incredibly exciting time in this field. Whether you’re talking about the emergence of the technologies, the ways to detect the earliest biological change. Whether you’re talking about the diversity of what we’re seeing entering into clinical trials. The idea that we’re not just targeting beta amyloid and tau, that we’re looking at the immune system, metabolism. The idea of combination therapies. Where we are in thinking about lifestyle and the role that lifestyle and behavior might play in terms of brain health, and impacting our overall risk.
Ultimately we want to have a– we want to be able to identify the people at the greatest risk. Identify the underlying biological changes, and when we have that intervention– whether it’s medication, lifestyle, or some combination. Being able to intervene at that earliest time point.
And as a field we’re talking about prevention. There are over five ongoing clinical trials right now that are working with individuals that are an increased risk, to say, if we intervene earlier, are we able to stop or slow the progression for these individuals and their families?
JOHN DANKOSKY: You know, I’ve gotten a chance to do a few interviews about Alzheimer’s drug therapies on Science Friday over the years, and I always have to ask people about funding and about the possibility of finding some of these breakthroughs. You know we just heard that Gene Wilder, the great and beloved actor, died of complications of Alzheimer’s. And it’s the sort of thing that people might read and it might draw more attention to them. Certainly many, many Americans have friends, family, loved ones who have Alzheimer’s disease.
I guess I just have to ask you doctor, why we aren’t making more progress? Or maybe spending more money to do the sort of research that will lead to a breakthrough?
DR. HEATHER SNYDER: Well, I think I’d answer that in two ways. The first is that it’s still a relatively young field. So when we compare Alzheimer’s disease to the other complex diseases like cancer or heart disease, we’ve been investigating those for decades– for centuries in some cases. When we think about Alzheimer’s– in fact, it’s about a 35-year-old field. Really in terms of about 90% to 95% of what we understand about the disease has been in the last 35 years.
And we’ve seen in the last five years– we’ve seen both an increase in awareness of the disease, but also an increase in funding. And that really came from the passage of the National Alzheimer’s Project Act in 2011, which the Alzheimer’s Association was instrumental in getting passed. And although it had no money at the time, we’ve seen incremental increases in funding.
And in fact the largest historical increase in research funding for Alzheimer’s disease came through in December of 2015 with an additional $350 million. Currently there’s a bill for an additional $400 million to be added into the base. So we’re just under a billion dollars at this point in time, and that would take us to the highest level ever of close to $1.4 billion.
JOHN DANKOSKY: Well, and we have to leave it there. And it’s good to hear that we’re getting some money to put at this problem. Dr. Heather Snyder, Senior Director of Medical and Scientific Operations at the Alzheimer’s Association. Thank you so much. I appreciate it.
DR. HEATHER SNYDER: Thank you.
Katie Feather is a former SciFri producer and the proud mother of two cats, Charleigh and Sadie.