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Bill Klaproth: So, what is therapeutic plasma exchange? This innovative therapy has the potential to slow down the rate of brain and body degeneration. It sounds like something we all want. So, let's learn more with Dr. David Haase, founder and Medical Director at the Maxwell Clinic.

This is the Top Docs Podcast. I'm your host, Bill Klaproth. Dr. Haase, thank you for being here.

David Haase, MD: Great to be with you, Bill.

Bill Klaproth: Yeah. So, this is really interesting. I'm excited to learn more about this. So, why would someone need a therapeutic plasma exchange?

David Haase, MD: Yeah. It's not something many people know about or hear about on a daily basis, and it's a very established medical procedure that is usually used to treat severe autoimmune disease, but now is finding some really interesting and useful applications to promote longevity as well as treat and reverse neurocognitive disease, which would be things like dementia.

Bill Klaproth: So, I could see a lot of people really being interested in this. This could really turn the tide or stem the tide of people with degenerative brain disorders.

David Haase, MD: Yeah, Bill. This is really one of the most interesting topics in all of medicine right now. And it's something that nobody should be surprised that they haven't heard of it before, because therapeutic plasma exchange is usually something that just exists inside major medical centers. It's a procedure where we actually remove the liquid part of the blood, the plasma, and then replace that plasma with a clean replacement plasma fluid, right? And so, that's really useful to somebody who has a very severe autoimmune disease, because what we're doing is cleaning out those autoantibodies from the body so that they're no longer attacking the tissue any longer. But what's interesting is that it's been found that this has many more effects than what are useful in severe autoimmune disease.

Bill Klaproth: Yeah, you said this is an established medical procedure. This goes on in major hospitals, so you briefly described the procedure. So, do you remove all of the plasma or just some? And what do you replace the old plasma with?

David Haase, MD: Yeah. So, let me just describe it to you in general, right? So when an individual has plasma exchange done, usually you have to get vascular access, that means you need an IV put in. Either you put a big IV in each arm or very large IV is put in the neck. And we actually are able to avoid that, which increases complications and challenges with plasma exchange, you know, the IV in the neck part. What you do is you put an IV in one arm and then the blood is pulled out. That blood gets mixed with an anticoagulant, so it doesn't clot together. It goes through a centrifuge continuously. And then, the cells, all the solid parts of the blood, the white cells, the red cells, and the platelets, those are separated from the liquid part of the blood, which we call plasma.

Now, inside the plasma, we have a major protein called albumin. But there's also all of the junk. There's all of the broken down proteins, there are messages of cellular aging, there are damaged molecules. All of that is in the liquid part of our blood and our body has to continually clean that up. So, that part is separated from the cells and then all the cells are then recombined with a purified plasma replacement product, which is mainly made of this same protein called albumin. So, that liquid then gets recombined, it all goes back into one IV line, and it goes back into the IV that could either be in the other arm. And this goes continuously, sometimes for an hour and a half or up to three hours. And we end up removing the equivalent of all of the plasma that the person started with, so that can be three to four to four and a half liters of plasma. It's really a remarkable therapy, quite safe. And it has some really interesting applications.

Bill Klaproth: So, it's your blood filtered and cleaned and then reinserted back into your body.

David Haase, MD: So, it's not really filtered. It's actually just the liquid part is separated from the cells and actually discarded and then replaced with this albumin that has been cleaned that has no risk of infection or there's no additional broken down cellular or molecular materials in that fluid, and that's what the replacement fluid is mainly made of.

Bill Klaproth: Got it. Have there been studies or clinical trials about the benefit of therapeutic plasma exchange?

David Haase, MD: Oh, yeah. Like I said, this has been around for a long time. We treat individuals with severe multiple sclerosis or neuromyelitis optica or many of the autoimmune conditions. There's lots of small studies done on this in very severe conditions. But the really exciting studies are the ones that are coming out with regard to Alzheimer's disease. There was a study called the AMBAR trial. And AMBAR trial is this study that should have blown the tops off of the New York Times. This one should have been shouted from the rooftops because it was a multi-national, multi-center, randomized controlled trial that looked at giving this procedure to individuals with advanced Alzheimer's disease or early Alzheimer's disease. And they did this. Individuals got a total of about 18 of these plasma exchanges over the course of about 14 months, and another group got a sham. Basically, they thought they were getting the procedure, but they didn't. And if you compare those groups, the individuals with this advanced Alzheimer's disease had over a 60% decrease in their rate of progression compared to the individuals who got the sham, that's 60%. And individuals that had mild Alzheimer's disease, there was a trend that they actually had improvement over the course of those 14 months. That gives more hope than anything that we have seen in the pharmacological world as a viable treatment to address this multi-system degeneration, that predominantly affects the brain that we call dementia. Super exciting stuff.

Bill Klaproth: So, why do you think this wasn't promoted or widely recognized?

David Haase, MD: Well, number one, if you're not up on it, you're down on it, right? If you're not aware of something, you don't have kind of the construct. The people who are listening to this podcast now know that there's this thing called therapeutic plasma exchange that exists. And guess what? They're going to start seeing it all over the place because they're now aware. But now, I have to even tell you, and you know, I went to Vanderbilt and Mayo Clinic, practiced in Mayo Clinic. I knew my stuff and I still was never exposed in my early years of training to therapeutic plasma exchange as a treatment, which surprised me. I was like, "Wow. I thought I knew the palette of what was possible in healthcare." So, this is just number one, not known to begin with. And therefore, there's no real advocates for it.

The other thing is plasma exchange, it's kind of a procedure in medicine that's a redheaded stepchild, no offense to the redheaded and stepchilds out there, because there's no one specialty that rules it. Nephrologists, neurologists, intensive care doctors, family doctors, internal medicine doctors, toxicologists, everybody uses this tool on occasion. Many specialties use this tool on occasion, but it's not like it's in the realm of cardiology or just neurology or just rheumatology. It's a broadly applicable tool, so it just didn't get as much recognition as it needed to. And it's kind of shocking.

Bill Klaproth: Yeah. Well, it sounds like this is a breakthrough and it's going to get traction pretty soon. So, what are some of the positive results patients see afterwards?

David Haase, MD: Bill, I don't know if it's that really the way we should think about it, right? Because all too often, yes, people see positive results with regard to some individuals have clearer memory, we've had reports of their vision being clearer, their attention being better, their mood improving. But what's more important than the symptoms is the system. How are you functioning at a cellular level? All too often in healthcare, we are focusing on a pill for an ill. "Oh, I have knee pain, so I'm going to take this pain eliminator pill," but the cause of the knee pain is still there and it's still degenerating.

And one of the things that is terribly under-recognized is how important aging is as a cause unto itself. Aging is the number one risk factor for deaths from COVID by like 20 times more than any other risk factor. The same thing goes with heart disease and cancer. Your aging is 10 to 20 times more important of a risk factor as anything else. And what's interesting about plasma exchange is it may actually affect the biologic process of aging at the genetic expression level.

Let me tell you a little story because this is super interesting, this may be one of the most interesting stories in all of medical science. At the University of Berkeley and at Stanford, MIT, they've run this experiment called Parabiosis. And this is where they took two mice, an older mouse and a clone of that mouse that was younger. And they sewed them together side by side, so they kind of shared a little flap of skin. And these poor little mice are attached to each other, run around the cage together. And a remarkable thing happened in about a week, is that the old mouse started to turn young. So, biologically, its muscles could repair after injury faster. And the liver, the fatty liver started to reverse. Osteoporosis started to reverse in this old mouse. The T-cell and B-cell, the immune cells started to act more like they should in a young individual. The hair started to grow in. And most interesting for me is that neurogenesis started, new neurons started to sprout when this old mouse was exposed to the plasma, really, of the young mouse. And that started this entire idea.

Irina and Michael Conboy are really the leaders in this remarkable studies. And then they went, "Well, hey, could this be done by a machine?" And so, they actually did essentially a plasma exchange on these mice. They said, "Okay, this old mouse, let's just remove some of their old plasma and let's just put in clean plasma, not young plasma, just even clean plasma." And guess what? Most of these same changes happened. So, they were able to change the very biology of aging through this process of plasma exchange in a mouse that was mimicking connecting a young mouse to an old mouse.

So, what's interesting is that we can measure those things in adults. So, you say, "Well, what changes happen? What do people feel?" Well, while what they feel over time may be very significant, what we can measure is that we have seen a very substantial improvement in the markers of aging of individuals that undergo plasma exchange. And we call that methylomics. So, there are specific tests that we can do that measure just how biologically old somebody is. And we've seen changes four and six years younger after a plasma exchange. And in our center, we have an IRB-approved research trial going on. It's the most advanced research trial of its kind where we're studying transcriptomics, methylomics, proteomics, I mean, lots of big words. But the bottom line is we're measuring everything we can possibly measure to understand why this works. It's pretty well agreed that this is happening. But now, we're trying to crack the code on why does it work, so we can keep doing it better and better and better.

So isn't that interesting? That is one of these stories that goes like, "You've got to be kidding me," that we are kind of as old as the signals that float through our blood that tell our cells how old we are. So if we change those signals, our stem cells actually start to behave younger.

Bill Klaproth: So, we can rejuvenate our cells like the young mouse and the older mouse. The younger cells rejuvenated the older mouse's cells. So, we can do that with therapeutic plasma exchange basically.

David Haase, MD: We have seen lots of evidence of that. I'm not going to make the claim yet, okay? We don't have an FDA-approved indication for this, but that's why we're studying it. And we have people that travel from across the United States and either other countries to work with us on this very opportunity.

Bill Klaproth: So, you said the FDA is looking at this. Do you foresee then a day where this will be FDA approved and that's probably when the mass market will really understand and receive this?

David Haase, MD: Well, just recognize everything we're doing, we're using FDA-approved machines, FDA-approved materials. All of it is FDA-approved. The FDA really doesn't approve a medical procedure, okay? What it is instead, is when is it going to be covered by insurance? When is it going to be covered by Medicare? That's the question. And so, this is really a matter of medical judgment as to when an intervention is applied. And that's where you have to weigh what are the potential pros, the cons the risks, the benefits, those are individual decisions.

Bill Klaproth: Right. So, you said earlier there was a test done where people were administered this over a period of 14 months. How many procedures do people normally get?

David Haase, MD: So, that's another one of the things that still is dependent upon what condition they have. An individual with severe autoimmune disease may need one of these procedures twice a week for months and months and months. Individuals that are trying to reverse cognitive decline, the frequency varies. But the AMBAR trial, like I said, there were 18 of these treatments that were done over the course of 14 months of therapy. And as it regards to longevity, it's very interesting. We see even a single plasma exchange has ongoing effects in the body measured sometimes up to six months later.

So, how long can one of these interventions last? It kind of depends upon the person that is being intervened upon. An individual who's really sick and really biologically old is going to take a lot more intervention than somebody who is really looking more for a tuneup. You know, if you're going to do an overhaul versus a tuneup, and that's kind of what we're doing, this is an oil change, right? It's an oil change for the blood.

Bill Klaproth: That's a good way to think about it. So, people are probably watching this going, "I'm in. Sign me up." But who is a good candidate? Who is not a good candidate?

David Haase, MD: Yeah. Again, these categories, severe autoimmune disease, you'd really work with your physician. But still even in autoimmune disease, this is an under-recognized opportunity. Some individuals with autoimmune conditions such as POTS and even long COVID, some of these have been addressed with plasma exchange.

For individuals with cognitive decline, we have another IRB-approved trial where we are investigating this and how the blood markers that are associated with Alzheimer's disease change over the time with plasma exchange. But individuals with cognitive decline, I think there's very good reason to suggest they should look into this.

And individuals that are looking to improve their health span. Aging is essentially when you have more degeneration than regeneration in any given time period. And so, the antidote for that is more repair. And what you do need repair for, you need your stem cells to do the repairing in your tissues where they live already in your body. If we can make those stem cells act younger, soup up, so they do more repair, the question is at what time is that appropriate to start? We have trialed this in 40 year olds. I really think that the cutoff is right around 45 to 50 years of age when people really start seeing benefits in the longevity space. And certainly, when you're starting to get about 55 to 60.

Aging really starts happening as soon as we stop growing and developing, and that's around age 25. So by the age of 30, every single organ in your body is declining in function. Every single organ is losing what we call organ reserve. And you know what? Everybody who's above that age, certainly if they've hit 40, already know that, right? Already know that.

And so, it's a really exciting time in longevity medicine. I think this has a lot of potential to address the most important risk factor for every chronic degenerative disease that exists, which is the biologic process of aging itself. So exciting.

Bill Klaproth: Absolutely. I'm just thinking about quality of life as we age. This is a tool to help extend that quality of life even further.

David Haase, MD: Well, even if we don't get more years, we should be shooting to get more good years, right? And here's the other thing, plasma exchange also gives us more evidence about how important lifestyle is. Because what we're doing here is we are essentially cleaning the blood, we're decreasing the amount of nasty things in there. And as a result, the body goes, "Ah, good. I can function better." So, eating clean, breathing clean air, drinking clean water, decreasing the stress in our life, exercising, these are fundamental. And in many ways, plasma exchange gives us some biologic proof that living a clean life has some real benefit to it. So whether or not you engage in the therapy itself, it should really be a marker that our bodies are designed to create health from the inside out. We are designed for that. We should be curious about how can we do a better and better job of enabling our bodies to do more repair in a day than that they would have. And that's exciting.

Bill Klaproth: Yeah, for sure. So as you're talking about that clean eating, living a healthy lifestyle, are there other therapies that you use along with plasma exchange that might be helpful? Kind of a one-two punch kind of a thing.

David Haase, MD: Yeah. We have a whole pathway that is dedicated to improving the safety of this procedure. One of the things is we probably have one of the highest rates of getting peripheral access, meaning being able to use IVs in the arms rather than these big catheters. And that's where most of the danger is with a plasma exchange. And then, what else goes in? We're studying that extensively. And we've had multiple different IV fluids and things like that to improve safety and efficacy.

I think there's going to come a time where we see stem cell products being used. I think we'll see a time where exosomes and plasma proteins, and there's going to be a whole host of additional improvements that will continue to come. And I think those are going to be very most important to be customized when appropriate to an individual. But I think the jury is still out exactly what is the best thing to add in. What we're really clear about is that cleaning up is absolutely essential. That the molecules that are floating around in an old person are creating the old, okay? We think the clock causes the old. But in many ways, it's the signals that the body is continuously exposed to that are perpetuating the biologic age of the cells. That takes a while to wrap your head around, but it's going to prove out to be accurate.

Bill Klaproth: Because we really beat our bodies up over time.

David Haase, MD: Well, listen, gravity's a bitch, right? And when we think about gravity, erosion, friction, oxidation, nobody's getting out of this life alive, right? Nobody's going to get out of this life alive, and that's a reality. But how can we have the very best days possible, right? How do we have less degenerative disease that causes disability and early death? I mean, I really am passionate about how do we stay out of that zone of disability. I mean, those multiple years where one doesn't really have control of their life, they don't really have enjoyment of their days and, you know, kind of just waiting for the universe to reclaim the parts, right?

Bill Klaproth: Yes. That's what we want to avoid. And this can help us to avoid that. So, how does someone get started in all of this?

David Haase, MD: Well, the first thing is really to have a consultation with our center. You can find us at maxwellclinic.com, that's M-A-X-W-E-L-L clinic.com, and schedule a consultation. I think this is in the realm of highly personalized medicine. There's no rubber stamp process for this. And I think it's very important to individualize these approaches. So, that's where we start, by listening.

Bill Klaproth: Right. So, you come up with a targeted plan then for each individual when it comes to therapeutic plasma replacement.

David Haase, MD: Correct, if appropriate. Like I mentioned, this is a very safe procedure. But I like this idea that plasma exchange is a lot like a snowblower. I grew up as a farm boy in South Dakota, right? And I blew a lot of snow. And man, snowblowers are wonderful. The driveway's all packed with a whole bunch of accumulation of stuff you don't want. And you take the snowblower and you blow it all out. That's great. And that's the same way a plasma exchange really does. Man, it can go in there and just clean out a whole bunch of buildup of things that you really don't want there. That's wonderful. And we should be trying to find the cause of the snowing and addressing all the underlying cause that we can do, or at least be mindful of that. And utilizing both of those therapies is, I think, the ideal.

Bill Klaproth: Absolutely. Well, you've given us some great visuals to hang onto. The oil change for the body and now the snowblower blowing all the bad stuff out, but we got to understand why it is snowing as well. Really great information, Dr. Haase. Anything else you want to add before we wrap up?

David Haase, MD: Well, I will say this, that the number one comorbidity, right? A comorbidity is a disease that occurs with another disease. That's what we call it in the medical world. The number one comorbidity for dementia, and even aging itself, is denial. One of the things so frequently people that have, well, they're losing a little bit of memory, they blow it off and they go like, "Oh, it's not really a problem," "Oh, it's a little hardening of the arteries," "Oh, it's a little bit--" You know, you deny, you distort, you do everything possible to not actually face what is happening. Aging happens, neurodegeneration happens. And to the extent that you can go, "Yup, I'm human, like all other humans, and I am subject to the ravages of time. And I can either choose to do something about that or I can put my head in the sand and continue to live in denial."

Denial is actually pretty rational if there's nothing you can do about it, right? And for many, many decades, we have been told that there's nothing you can do with regard to neurodegeneration. There's nothing you can do with regard to changing your biologic aging pathway. And that's BS, I believe. But then, once you recognize that, it takes a lot of bravery. It just takes a lot of bravery to say, "Huh, I have a problem." And then, to reach out and ask. And then, oftentimes, a lot of physicians are still in that belief system that there's nothing that can be done. And so, they ask and they go like, "Oh, well, there's nothing that can be done. I shouldn't have even asked." And then, they proceed on to their curve of degeneration and aging that they have been on.

So, I just want to encourage everybody don't let denial become your demise. And encourage curiosity when it comes to how you can live your life more fully both from a standpoint of how long you can live it and how well you can live it. Be curious because we live in an amazing age. So many new things are coming forth that actually can make a difference. So, I feel so privileged to get to be alive at this point in time and get to practice medicine. I love practicing medicine, I love my patients, but it's just an amazingly wonderful time to get to be alive.

Bill Klaproth: And don't let denial be your demise. Very well said. Dr. Haase, this has really been fascinating and informative. Thank you so much for your time. We appreciate it.

David Haase, MD: Thank you, Bill.

Bill Klaproth: And if you found this podcast helpful, please share it on your social channels and check out the full podcast library for topics of interest to you. This is the Top Docs Podcast. I'm Bill Klaproth. Thanks for listening.