Could Viagra Lower Your Risk of Alzheimer’s Disease? with Feixiong Cheng, PhD

A Cleveland Clinic-led study shows that Viagra, the “little blue pill” used to treat erectile dysfunction, may offer protective powers against Alzheimer’s disease. Researcher Feixiong Cheng explains how the medication might make a difference against this form of dementia.

Transcript

John Horton:

Hey there, and welcome to another Health Essentials Podcast. I'm John Horton, your host.

Viagra® might qualify as one of the more well-known medications, given its, well, uplifting abilities. But the little blue pill commonly used for erectile dysfunction may have another power: the prevention and treatment of Alzheimer's disease.

Cleveland Clinic-led studies have shown that patients who took sildenafil, more commonly known by the brand name Viagra, were 30% to 54% less likely to be diagnosed with Alzheimer's disease. To learn more about this groundbreaking research, which is still very preliminary, we're joined today by Dr. Feixiong Cheng.

Dr. Cheng led the studies and is the founding director of Cleveland Clinic's Genome Center. His research is dedicated to using systems biology to unlock genetic and genomic mysteries influencing health and disease. Now, let's find out how his work on Alzheimer's might eventually make a difference in your life or the life of someone you love.

Welcome to the podcast, Dr. Cheng. Thanks for stepping away from the lab for a few minutes to talk about your research.

Dr. Feixiong Cheng:

Oh, you're welcome. Very happy to be here.

John Horton:

Well, to get things started, let's spend a few moments just talking about Alzheimer's disease, which has really, I know, been a focus of your work here at Cleveland Clinic. What drove you to study that progressive brain condition?

Dr. Feixiong Cheng:

Of course. So my graduate training background work on medicine or chemistry, really focused on drug development. And I did a post-doc training across Vanderbilt in Nashville and also Northeast in Harvard Medical School out of Boston. Work on the bigger data for system biology study for drug discovery. So I built my own lab at Cleveland Clinic in 2018.

John Horton:

Wow.

Dr. Feixiong Cheng:

Yeah, about seven years ago almost. I choose Alzheimer's disease as a lab in a research area because about a decade ago, my grandpa, [grand]father was … died by Alzheimer's dementia. So I have really patient-family experience, know how terrible it is for this disease. So this is why I chose to study this disease about seven, eight years ago.

John Horton:

Oh, wow. Yeah, I mean Alzheimer's is … it is a disease that affects so many of us through the people in our lives. And that's really something that kind of drove you into trying to find some solutions.

Dr. Feixiong Cheng:

Exactly. I would say Alzheimer's disease is not different with other diseases. It's not an impact for the patient only. They also impact the entire patient and the patient's family as well. So this is a really big health crisis for our healthcare system in particular, dealing with the aging populations right now.

John Horton:

Oh, definitely, definitely. So as you start this search and you start looking for solutions for Alzheimer's, how do you end up looking at Viagra? Given what most of us know about the little blue pill, that seems like quite a jump to get there.

Dr. Feixiong Cheng:

Yes, I would say this is a long … I would say long topic I'm happy to share with you. But it is definitely is really a teamwork. I'm happy to share with you as well.

So we come out of this idea about four and five years ago when we started this project. So we went to all current Alzheimer's, like a drug developer pipeline, to see what are the problems we have, and it interestingly come to us. For example, Alzheimer's is a really complex disease or multifactor disease, and people try many, many way for therapeutic discovery. For example, people try key Alzheimer's protein they call amyloid protein, is a hallmark for Alzheimer's, and people try drug discovery couple years. The drug success rate is a pretty low. Majority control were failed by anti-amyloid. But the good news, last couple years, 2023 and 2024, two FDA-approved anti-amyloid antibody was approved. I think this is really encouraging.

And another idea people also try — they call tau protein — is another hallmark for Alzheimer's. And the people try almost 10 years, and so far, we don't have a success yet.

So about four and five years ago, we discussed with my fellows at Cleveland Clinic, we come out as simple idea, is we don't want to target the single protein like amyloid and a tau protein alone. We come out a more system-based approach or system biology-based approach, targeted the amyloid and a tau protein at the same time because this is a multifactor disease. And we propose this idea to the NIA, or National Institute on Aging, federal agency. And we are lucky we get a funding for about three to four million. Funding to support to test our idea, and then, we come out Viagra fundings.

John Horton:

Yeah. Now how much of it is related to Viagra just increasing blood flow? Because I know that's kind what the pill is known to do. Is that something that plays into how it might be sort of a preventive role against Alzheimer's?

Dr. Feixiong Cheng:

I think so. What we did in our project is we used the bigger data approach to screening all — like 1,600 FDA-approved drugs. But surprisingly, the Viagra or sildenafil come out very top even in our top 10 predicted drugs. And then, based on your explanation, we see Viagra also increase the blood flow and the people see neuroprotective effect for other disease. This is why we choose Viagra for our further study.

John Horton:

And it seems like that's pretty common, where there's a medication that's used for one thing and we start looking at it in a different way and find it might have more applications.

Dr. Feixiong Cheng:

Exactly. And this type of idea people call “drug repositioning.” So I tried the drug repositioning project for multiple diseases beyond Alzheimer's, almost like 15 years right now. And we identify multiple drug candidates. But I'm very excited about this story, Viagra. And sildenafil, we discovered about, we published in 2021, about three years ago, initial agents.

John Horton:

Now from your research so far, how effective might sildenafil be against Alzheimer's?

Dr. Feixiong Cheng:

Yeah, this is a really good question. So far, for Alzheimer's drug discovery, we don't have good a model to test this kind of idea. So what we did in our project is we use the larger scale retrospective patient data analysis. For example, we use the health insurance claims data. When patient see doctor and the doctor send this kind of information to health insurance company. And the insurance company have this kind of claims data for millions or even hundreds of millions of patients.

So we use this bigger data. We find interesting is if people take a Viagra, compare people don't take a Viagra, have a similar age, have a similar male and a female, and also have a similar disease burden. We found if people take a Viagra, it's also shared with a reduce about 30 to 50% risk of Alzheimer's compared to patient they don't take a Viagra.

John Horton:

That's really incredible and potentially just groundbreaking if taking that can somehow offer a little bit of a protective effect against the onset of Alzheimer's.

Dr. Feixiong Cheng:

Yeah, but I have to share with you, or even in this audience as well, is our study, it's still retrospective analysis. It's not a clinical trial. So this 30 to 50% reduction may also be driven by possible co-funding factor as well. We must be verified in the clinical trial, like a random control, to further, to confirm the benefit for patients.

John Horton:

Right. So it sounds like what you found was when you looked at all these different cases with people who have taken Viagra, there was just kind of, I don't want to say coincidentally, but they also had a lower percentage of Alzheimer's. So now, it's a matter of digging in to see whether it's truly related or if there's a bunch of other factors driving that.

Dr. Feixiong Cheng:

Yes.

John Horton:

How might Viagra work to guard against Alzheimer's? When I was reading some of the studies, there were things about protein clumps and neurons. And there was a whole lot going on there. So can you break it down for us a little?

Dr. Feixiong Cheng:

No problem. Right. I would say, like I mentioned before, the Alzheimer's is really a multifactor or complex disease. And Viagra, I would say, is also magic drug as well. They also have a multifactor effect in our human body as well — beyond just increase the blood flow in our human brain, may have protected effect for Alzheimer's.

In our basic research, we also show that, for example, we use the patient's stem cell, they call iPS cell. We can derive to the neuron, use this kind of technology to get a Nobel Prize 2016. And what we find is Viagra treatment, this iPS cell-derived neuron, they have a neuroprotective effect we show. And they also can reduce a key Alzheimer's hallmark, like the tau protein, like a phosphate tau protein. I apologize for this kind of research term, right?

John Horton:

No, no, but that's what we're trying to get into. So it sounds like it changes some things a little bit within you to maybe slow the progression or kind of prevent it from happening.

Dr. Feixiong Cheng:

Exactly. Beyond just our common knowledge about increase the blood flow, we also show in our basic research, mechanistically, Viagra also can targeting the Alzheimer's biology. For example, neuroprotective effect, we see neural tight growth. Also reduce the tau hallmark protein phosphorylation as well. Really support the benefit we see in the retrospective patient data analysis as well.

John Horton:

It sounds like it's so hard to try to narrow down what causes Alzheimer's because, like you said, it's multifactorial. There's so many things playing into it. But it sounds like from what your research has shown, Viagra kind of, it starts getting into those neurons and just the chemistry inside you. And what it's doing is kind of tamping down some of the forces that might lead to Alzheimer's development.

Dr. Feixiong Cheng:

Exactly. This is the beauty for drug repositioning we just discussed before. Viagra is a drug originally developed for erectile dysfunction, but they also have other multifactor effects like we discussed. And then, this can be useful for Alzheimer's as well. We see many, many other examples for other type disease as well.

John Horton:

Well, and I think as we talked about earlier, I mean Viagra didn't start as an erectile dysfunction drug. I think it started as a heart medication, right?

Dr. Feixiong Cheng:

Yes, yes.

John Horton:

So it's already been reused.

Dr. Feixiong Cheng:

Exactly.

John Horton:

So when we start looking at possibly using Viagra to help prevent Alzheimer's, if that's possible in the future, would this be a treatment that would be possible for men and women?

Dr. Feixiong Cheng:

Oh, yeah. This is really critical question. So in our original study, we only show very strong reduction effect in men because Viagra originally approved for erectile dysfunction. But Viagra is also off-label use for pulmonary hypertension as well. It's also FDA-approved.

So in pulmonary hypertension patient, we also have a small number of women as well. In our original study, we also see Viagra also with a reduced Alzheimer's in women, but no statistical significance because the small population for women's. Yeah.

John Horton:

So it sounds like you saw some of that. It may have some protective effects but it's a much smaller sample size, so it's hard to draw a lot of conclusions from it.

Dr. Feixiong Cheng:

Yeah. But in our new publication we just published in 2024, we look at both like a man and a woman iPS cell, this stem cell derived from both men and a woman. And then, we see the similar effect as well.

In our animal study, we didn't publish yet, we look at both male and female mice, Alzheimer's disease mice. We see the same effect as well. But we need to further confirm in the future, like a clinical trial study.

John Horton:

As we talked about when we talked the other day, and there's still a lot of research to do.

Dr. Feixiong Cheng:

Exactly.

John Horton:

But it does seem like everything that we're finding is, it's in the direction we want it to go. It's just now a matter of making sure and verifying, dotting the I's and crossing the T's, I guess, as the phrase goes.

So I have to tell you, it's fascinating to think that a drug originally designed for a completely different purpose, it might have such potential for Alzheimer's. As we start looking at this, though, are there also some risks or side effects associated with Viagra and maybe using it this way?

Dr. Feixiong Cheng:

Yes, yes. So I would say overall, Viagra is a pretty safe drug for healthy people, but we need to still really be careful about a potential side effect for some people if they have underlying condition. For example, if some individuals, they have a cardiovascular problem like low blood pressure, Viagra still can cause low blood pressure, as well have potential side effect. Or have potential of the worst drug-drug interaction if you take other drug together. So this something you need to really be careful, you have to consulting with your primary doctor, as well about this kind of potential side effects.

John Horton:

And I have to ask, too, given that Viagra is obviously more commonly known for what it can do with maintaining erections, is that also a potential side effect that could come if you're taking this for Alzheimer's?

Dr. Feixiong Cheng:

I think so. I would say for Alzheimer's patient, we need to more be careful because Alzheimer's patient overall is pretty sick and it is also older individuals. They have more disease comorbidities, like a cardiovascular problem, hypertension problem. When you take Viagra, you need to really be careful because most older Alzheimer's individuals, they take multiple drugs at the same day. So when you take this type drug in the future, we'll really be careful as well.

John Horton:

Yeah. And that's what's got to be hard with trying to figure this out. As I understand it now, it's not like Viagra is something you take daily, like every morning with breakfast. It's something you're taking for a certain occasion for a lot of people.

And so I guess, trying to narrow down how you would use it with Alzheimer's. If you make it a regular thing or a smaller dose, maybe you get some of those protective effects. I'm guessing those are all things that you're looking at with your research.

Dr. Feixiong Cheng:

Exactly. This is something we work very hard with our Cleveland Clinic physicians. Try to conduct the clinical trial right now. We are really actively working on that in the past two years to design our clinical trial in more rational way. Including the dosage, including the frequency. Because Alzheimer's patient, they have a dementia, they cannot take a drug multiple times per day. We only try once or twice per day, as well to help this particular disease population.

John Horton:

Now, when you're looking at this, I know a lot of the research has shown that people who took it were less likely to have Alzheimer's. So are we looking at this more as maybe a potential preventive medication? Or is there hope that could also be used maybe for treatment once you have it to maybe slow the progression of the disease?

Dr. Feixiong Cheng:

Oh, this really good question. I think our current research cannot really determine is the prevention and treatment or disease modifying or treatment right now. But our data is more support preventive effect in the current stage.

For the treatment effect, we have more research to be done, in particular, clinical trials. Like a randomized clinical trial to be done to see the possible delay of the progression in the future.

John Horton:

Well, I guess the good news is if you prevent it from coming on, maybe you're not going to need as much treatment. So that would be a good thing.

Dr. Feixiong Cheng:

But yeah, this is good things, I agree, for our healthcare system. But today, even in our United States, we still have 6 million Alzheimer's patients we need to treat as well.

John Horton:

Yes, yes. So it seems that we've seen some promise when it comes to Viagra possibly protecting against Alzheimer's. How far might we be where the research may actually allow Viagra to be prescribed to prevent Alzheimer's in some way?

Dr. Feixiong Cheng:

Oh, yeah, this is a good question. This is really dependent on the process for our clinical trial study we work on. I really hope, beyond us, many, maybe other physicians, also can testing Viagra in the patient in other clinical trials together as well.

So about the possible timeline, we are conducting the possible phase two trial to test Viagra. Usually, it will take two or three years. We will get the preliminary results to see the possible effect. If you're really waiting for final phase three trial, may take longer. I cannot give exactly timeline right now.

It will take years before we can come. I hope you understand that this is how complexity for the research we work on right now.

John Horton:

Yeah, it sounds like there's a lot to do. So bottom line is nobody's going to be able to go into their doctor tomorrow and ask for a Viagra prescription for Alzheimer's. They're going to have to show a little patience and see where this research goes.

Dr. Feixiong Cheng:

Yeah, exactly. So what we work on right now is really active. Get the federal funding or even other type funding support for this clinical trial get started. When we get this clinical trial started, the patient can be enrolled in our clinical trial to receive this drug, as well to see the possible effect.

John Horton:

Well, I have to tell you, Dr. Cheng, this has been a fascinating discussion.

Dr. Feixiong Cheng:

Thank you.

John Horton:

And one that I'm sure offers some hope for many, many people. So I want to say thank you for the work that you and your team have done on this so far to maybe kind of crack the code and maybe stop or prevent Alzheimer's.

Before we kind of part ways, though, and you go back to your lab to do all this important work, do you have any advice or just words of encouragement to share with anyone who's dealing with Alzheimer's?

Dr. Feixiong Cheng:

Of course. So I would say Viagra is just the one type example or research project we work on in a lab supported by federal funding or our institute. We work on many other types of therapeutics, we work on right now. Hopefully, we can publish this results.

Another news I want to share to the Alzheimer's community as well — they have multiple drug, people testing in phase three trial as well. We really hope next few years, some drug really show the real effect in future and get FDA approved as well.

But I really wanted to share to the Alzheimer's patient or patient family as well, Alzheimer's is complex disease. Beyond a treatment you mentioned before, I think prevention is still the good strategy right now.

For example, beyond just Viagra we discussed, if we can control the BMI really well, keep with the healthy diet, sleep really well, control your blood pressure and cholesterol really well — this is all risk factor for Alzheimer's. And you are more likely to reduce your likelihood to get Alzheimer's in the future as well. I really encourage our community to take this kind of small step to help to prevent even ourselves for potential Alzheimer's in the future as well.

John Horton:

Yeah, it does sound like with so many things that we talk about on this podcast, if you lead a healthy life with a healthy diet and exercise and get enough sleep, it seems like your chances are so much better to avoid some of these diseases that we all kind of fear.

Dr. Feixiong Cheng:

Yep. I totally agree.

John Horton:

All right. Well, Dr. Cheng, once again, thank you so much for taking-

Dr. Feixiong Cheng:

You're welcome.

John Horton:

…some time to talk with us today. And again, thank you for all the work and research that you are doing. I look forward to having you back on to talk when we can give two thumbs up that this is ready to go.

Dr. Feixiong Cheng:

Thank you so much. If we get a clinical trial research done in the future, we're happy to talk with you further.

John Horton:

Thanks a lot. Have a great day.

Dr. Feixiong Cheng:

Thank you. Bye-bye.

John Horton:

Alzheimer's disease currently affects over 6 million Americans and that number is expected to triple in the next 25 years. It's clear there's a need for prevention strategies, and studies suggest that Viagra could possibly fill that role. Stay tuned as Dr. Cheng and his fellow researchers continue their work to see if it's a viable solution.

If you liked what you heard today, please hit the subscribe button and leave a comment to share your thoughts. Until next time, be well.

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