Therapeutic Plasma Exchange: A Game-Changer For Parkinson’s

David Haase, MD

Thank you very much for having me. I have learned very much from you over the years as well. It’s a great delight to get to be here and spend this time together. Yes. I operate the Maxwell Clinic in Nashville, Tennessee. We’re celebrating our 20th year this year, providing functional integrative systems medicine. It’s just a pretty big deal. We have nine clinicians and a large center here that does some very innovative and deep work for people. Oftentimes, people have big problems or big goals. Find their way here. I grew up as a dairy farm boy in South Dakota, and it was that background. When I encountered the field of medicine, I realized that, wait a second, medicine was kind of the medicine I was being taught at Vanderbilt. The Mayo Clinic was a medicine for soldiers. It was a medicine to let us fight disease. Let’s wage a war on something. We use drugs that are anti-this inhibitors or blockers. It’s a very aggressive kind of way. My farmer tendencies just recognized that. Wait a second. I came to medical school to learn how to create health and how to grow health, kind of like a farmer would tend the land, and I guess it paid off because patients do get better on their own if you don’t mess them up, as the most important thing is not engaging in something that can harm you. But that just took me down a path of health coaching and, in my early days, functional medicine, integrative medicine, and holistic medicine. and then focusing the last 15 years on brain health because that’s where it’s at. You don’t have a healthy brain, and you don’t have quality of life. The brain is so important, and you are doing the lifestyle behaviors and making the changes that are necessary to change the trajectory of your life. I got very interested in the quality of EEG and neurofeedback, which we do a lot of here at the clinic as well. and then that led to my patients getting older and more and more patients with neurodegenerative diseases. I have to wrestle with that. We’re one of the study sites for the Evanthea trial that is starting up, which is the landmark clinical trial, a randomized controlled trial on the precision medicine approach to reverse cognitive decline. We place a great emphasis on it. I want to help us understand these complex cognitive diseases as things that are treatable by understanding the underlying problems that are causing them to occur and progress. That led me to plasma exchange, interestingly enough, because I was trying to figure out exactly what I could do to impact aging. But I think we’ll get to that later.

Kenneth Sharlin, MD

Let’s start with that big question, which is can you explain a little bit about what is aging? How do we understand aging? Because I think that’s as I  from what I get, that’s at the center of what therapeutic plasma changes all about.

David Haase, MD

You have it correct. A lot of people don’t get that it is about how we reverse the process we call aging. When could people say, Well, you can’t stop aging? Well, just think of all your 60-year-olds; some six-year-olds look like they’re 80. Some look like they’re 40. Right there, there’s a huge variation in how we age. I define aging as more degeneration than regeneration at any given time. What you can do to affect aging is to have more repairs or fewer breakdowns. And since Parkinson’s and Alzheimer’s disease and gosh, every major chronic degenerative disease has as its major risk factor aging, it makes a lot of sense to try to understand it as a process and how we can start to address it from a holistic basis, not treating just one organ, but what are the things that are going to make a difference? I had a patient of mine, a deep dive patient, with a sea-level employee at a big Silicon Valley company that has invented things all of us know. I asked her, “What do you want to accomplish by working together?” He said, “Well, I want to live forever.” I was taken aback. I was like, “Oh my God, somebody said it.” Because I kind of knew who this person was, I was going to say that maybe I should just suspend my disbelief for a little bit and dig into the longevity science. That’s when I came upon parabiosis. Parabiosis is an interesting science. It’s very solid that in many institutions, basically showing that if you take an old mouse and a young mouse that are clones of each other, put them together by their sides, put them back in the cage, and let them run around, connected. Amazing things start to happen. After about seven days, that old mouse starts to turn young. Their liver starts to regenerate. The fatty liver reverses, osteoporosis starts to reverse, the skin becomes healthier, the sense of smell returns, and the muscle’s ability to repair after injury reverses the T cells and B cells. The immune cells all start to function as if that mouse were young, and you get new neurogenesis. Then it’s just a ridiculous list. That means you’re reversing aging by being exposed to old cells in a young environment. If you let those mice continue to run around for a while, separate them. After about a month or two, separate them. The young mouse lives to its normal lifespan, and the older mouse lives closer to the lifespan of the young mouse. You get an age extension, and this is like a mind-blower. In the realm of longevity science, this is something that is you, and we can mimic that through this process. We believe we can mimic it through this process of plasma exchange. because we’re certainly not going to. I don’t know if anybody has a young clone that we can sew on or anything like that; that’s pretty much out of the question.

Kenneth Sharlin, MD

That’s science fiction. Was that Robin Cook almost in a coma where they have bodies and then they harvest organs from these people and put them into sort of therapeutic, animated suspension, or whatever? That’s a crazy thought. But so much science fiction sort of predicts the actual future. Here we are with ChatGPT and all these other things: talking to our computers, getting more intellectual answers than what we would get from a list of responses from a Google search box. It is happening. Hopefully, it’s not happening because we’re creating clones of ourselves and harvesting their organs.

David Haase, MD

But no.

Kenneth Sharlin, MD

We do things that are much more on the ethical and acceptable line, like therapeutic plasma exchange.

David Haase, MD

Yes. It’s nothing like that yet. Therapeutic plasma exchange is a very conventional therapy. It’s been around for a very long time. It is the standard of care in a hospital, and somebody has a very severe and progressive autoimmune disease. You need to stop myasthenia gravis, neuromyelitis optica, or a host of other neurologic, kidney, and bloodborne problems. Plasma exchange is simply removing the liquid part of the blood that contains antibodies, albumin, and potentially a lot of other toxins and things like that and replacing that fluid with a replacement fluid of some type. Usually, that replacement fluid is pharmaceutical albumin, which is a standard product that we get that’s been cleaned. It is the major protein in the liquid part of the blood, and plasma itself can be a replacement fluid.

Kenneth Sharlin, MD

It comes from donors who donate blood to a plasma donation center, and then they separate and take the cells away. Is that correct? then you can get a therapeutic albumin product. We all have albumin in our blood. It’s a carrier protein.

David Haase, MD

Yes. Is it like the plasma donation centers? What those companies are most interested in the plasma for are the antibodies that are in the plasma that are used in many other conditions. It happens to be more expensive. Albumin is the other part, the protein that is in the blood, and it’s cleaned extensively and kind of regenerated in the process of being prepared for distribution. Think of it like a blood oil change. You’re getting an oil change for your bloodstream. When somebody comes in, and has a plasma exchange done, which I may be jumping ahead of us ourselves a little bit here, but you can imagine it’s like that mouse in some ways. But we put an IV in each arm. The blood comes out of one side and goes into a centrifuge. It’s continuously running those red cells; all the cells of the blood are separated from the liquid part of the blood, the plasma. Then the red blood cells are kept and mixed with this clean replacement fluid. Then all of that goes right back into the body. When we run that, it takes about two and a half hours and ends up being about three and a half liters of plasma that comes out. That’s what we call a total plasma exchange. That is mimicking what happens with that young mouse being attached to the old mouse. It turns out that the basic science of this is very good and that when you do a plasma exchange, it changes the behavior of stem cells body-wide. 

Here, what’s very interesting is that stem cells, which, remember, aging is more regeneration than degeneration. Well, your stem cells that live in your tissue, your stem cells, when you cut your hand open, just knit themselves back together because the stem cells in that area, the progenitor cells, activate, and they do the job of making new tissue. Well, that’s those stem cells that are already in your body. Your stem cells are the most important cells to keep healthy, and they are dependent on your environment. This is a breakthrough understanding: old stem cells will behave young if they have a clean environment or a young environment. Young and clean are pretty synonymous. It turns out that when you do a plasma exchange, it’s not only removing toxins, misfolded proteins, degenerative substances, and autoantibodies; it’s also removing all those things out of the body, but it’s also creating a clean environment. a clean environment changes the behavior of stem cells body-wide, which improves cellular healing. That’s what’s quite remarkable here. if you can heal the blood vessels. Every neurologic disease has a vascular component to it, I believe, and people with great blood vessels and blood vessel flow are going to be more resistant to progression, or they can even have better improvements if their blood vessels are healthy. We know that plasma exchange does a lot and has a lot of benefits in improving vascular health, which then, I think, trickles out into the rest of the system as well.

Kenneth Sharlin, MD

Yes, we’re getting ready to start a clinical trial with a compound that’s already approved in South Korea. It’s not approved in the United States yet, which is the reason for this phase. It’s a phase-three trial. If it is successful, the company will apply for FDA approval, and then it will be a commercially available product. Well, folks may just chuckle a little bit, and I know you’ll be quite familiar with this when I tell you, but the mechanism is what’s called a phosphodiesterase inhibitor, which we know under the commercial name of Viagra. Now, this is not Viagra that we’re testing. I’m not encouraging folks to go talk to their doctors about Viagra unless they need it for what it is appropriate for. That’s a personal decision. But what do drugs like Viagra do? Well, they dilate blood vessels. In this case, if we have a compound that can cross the blood-brain barrier and improve blood flow down to the microcirculation, then it can essentially provide an exchange, if you will, to borrow from your technology of materials, whatever they are. In other words, bring in the good stuff and take out the bad stuff. Then we may have something that we can potentially apply to, in this case, treating Alzheimer’s disease. in phase two trials. Indeed, it was found to not only lower levels of the so-called insoluble amyloid protein that starts at least play a downstream role in the genesis of Alzheimer’s disease. But folks had improvements in their cognitive function, whereas the monoclonal antibodies that we are going to see over the next six to 12 months become commercially available only slow the progression. They don’t improve cognitive function. We’re pretty excited about that. But I was just sharing that because, again, it’s about blood flow; it’s about metabolism. It’s about signaling molecules.

David Haase, MD

Yes, I love what you said. It is about, I say, there are only four things we ever do to create health. We either remove something bad, we replenish something good, we retrain something dysfunctional, or we repair something that’s been injured. That is, the fundamentals and good blood vessel flow are at the center of all of those being able to occur.

Kenneth Sharlin, MD

Let’s talk about the therapeutic plasmid change and how it could treat Parkinson’s disease.

David Haase, MD

What’s so interesting is that when I first started doing plasma exchange, I had a patient of mine who had been seen for many years, and his Parkinson’s had been stable. He came to us. He had a large degree of improvement. Then he had been stable, and I and he had been together for a long time. I love my patients. I love the practice of medicine. I involved him in what we were doing and why we were doing it. I was getting ready to address Alzheimer’s as my major focus because it’s been a while. But at that time, Ambar had not yet been published. But there’s good data around plasma exchange and the treatment of Alzheimer’s disease. So I discussed that. He said, “Listen, I want to do that plasma exchange. I want to get my stem cells healthy. I want to do this.” “Oh great, well, that’s reasonable.” But I said, “Okay.” Now this is how we’re trying to help cellular health. We’re trying to improve your cellular health. But let’s say I don’t want you to have any big expectations of what’s going to occur, and Parkinson’s is a challenging condition to study. that better than anybody, because it has a large placebo effect concerning new therapy, which is kind of our key to seeming to have a big effect. Well, what was I saying? We’ll see what happens. We did our first plasma exchange, and he called back the next day, he said, “Wow, I had the best night’s sleep I’ve had in a long time.” Then his wife called back the next week and said, “He went out, and he started gardening again. He hadn’t gardened for three years. He went out, and he started playing the piano that week again. He hadn’t been playing the piano for some time. He went back to the board room, got re-involved in his company, and they took his wife out on a date, which they hadn’t done for many years.” And, as he said, “I just feel a lot better.” What was very interesting about him, just as a side note, was that his blood was quite thick. I think he had more of a hyperviscosity issue as part of what was going on with him. I got into a test. We have a device in our clinic to measure capillary function and glycocalyx thickness, and things like that, to better understand that. We’re studying that. But what was very interesting was that I did not expect to see acute improvements, and those improvements stayed. This was somebody who hadn’t tried a lot of things, and he would never get very excited about anything. He didn’t have much change. We were very happy with the initial improvement and stability. and so he was like, “Wow, I had this big functional improvement.” And then he maintained that until COVID hit and he wasn’t able to do exchanges for some time. then, after about six months, started to decline again, and it was very interesting to go to see this in a person I knew so well and had tracked for so long for this real improvement in function as a result of plasma exchange. I continue to say that this is not something with some fancy proprietary drug. There’s not a pharmaceutical company that’s going to fund the research here. We continue; like I said, we have four IRB-approved trials going on right now and different things in the clinic. We’re looking for grants, but in the meantime, we’re continuing to treat patients with Parkinson’s. Because we know that plasma exchange may have benefits, we believe it does. But we know that what plasma exchange is is the best proof, I think, of how important the functional integrative medicine approach is. Because what happens when people have a plasma exchange is that we give them clean blood. and so you create a clean environment for the stem cells, and therefore the body starts to create health. Well, that’s the same thing that we do in our everyday work of cleaning up the diet. Make sure you bring in good things, don’t bring in bad things, have community exercise, and sleep well—the fundamentals that need to take place regardless. But we’re very excited about the potential here for making a difference in both quality of life and slowing progression further.

Kenneth Sharlin, MD

We just need to let folks know that what we’re talking about—this therapeutic plasma exchange—is a treatment that, as Dr. Haase has said, has been around for a very long time. I’ve used it many times myself, just as a general neurologist, in treating conditions like Guillain-Barre syndrome, in the emergency room, and then in the neuro ICU. People come in during the winter, and they’ve had the flu, and then they suddenly realize that they’re getting very weak very quickly. It is the standard of care in many situations. He mentioned myasthenia gravis, another condition called CIDP. What we’re talking about is a little more investigational. We can certainly utilize approved treatments for things that are not necessarily mainstream uses of them. Physicians write prescriptions all the time for off-label use of the drug, but what Dr. Haase has done is gone the extra mile and worked through what’s called an institutional review board, or IRB, because there is such a huge commitment in our country to practice ethical medicine. We have to follow something called good clinical practice, or GCP. I’m sure he’s been through all that important training himself because there is a history of less-than-ethical training in our distant past. But just so folks know, this is not something you’re probably going to go to your regular neurologist for. This is still investigational, but it is very promising and extremely science-based, as he’s shared with us. There is quite a bit of literature on both young plasma infusions as well as therapeutic plasma exchange.

David Haase, MD

I think it would be useful to add here that the data on Alzheimer’s disease is quite remarkable. An individual that had this was called the Amber trial, and that was a multinational, multicenter, placebo-controlled randomized study looking at: What’s the effect of doing plasma exchange on individuals with Alzheimer’s disease? Since there’s so much crossover among the neurodegenerative conditions right now, so much crossover concerning, there are very few pure cases that exist out there. What was shown is that over 14 months, individuals with moderate Alzheimer’s disease had a 60% decrease in the rate of progression of their condition. That’s a very, very meaningful change. But it was very interesting to see why.

Kenneth Sharlin, MD

Is the benefit twice the benefit of the currently poised-to-be-approved drugs?

David Haase, MD

Correct.  with almost very little and drastically less risk for side effects. But what was interesting is that in the subgroup with mild Alzheimer’s disease and there wasn’t again, the study power still needed to be higher in these individuals. However, in mild Alzheimer’s disease, they had improvement over those 14 months compared to their baseline and certainly an improvement compared to placebo. Going back to a principle, the earlier we can address cognitive disease and neurodegenerative disease, the more likely we will have improvement. Denial that there’s a problem is one of the worst comorbidities that exist. One of the things that makes a disease worse is denying that there’s a problem. The Amber trial, which had a barely static presence in the bean counters and statistical significance, missed one factor. It was needed to have 0.05, and it was 0.06. Otherwise, I think everybody would have heard of this everywhere. But every primary factor, every primary endpoint, and every secondary endpoint was met except one by a hair breath. I don’t think we’re going to get to see this trial done again because it was so expensive. It took so long. There’s not a special interest group that’s going to drive this forward. I dove into doing plasma exchange, realizing this data, and feeling like I didn’t believe this was investigational any longer. Can I say that, from an Alzheimer’s standpoint, this is good clinical practice? One of my goals is for us to relook at Amber. I think it’s a terrible thing that we didn’t give that study the attention it deserved, because plasma exchanges, when done in the right hands and with appropriate safeguards, are an incredibly safe therapy, and it feels like a moral obligation to make sure this is available.

Kenneth Sharlin, MD

We have heard from Dr. Haase about the importance of early identification of the problem and whether it is Alzheimer’s disease. to borrow from Dale Bredesen, getting your cognoscopy, or that’s Parkinson’s disease, where if you’re seeing some change in your posture and you’re seeing some change in your mobility if you have a change in your sleep quality where maybe you’re acting out your dreams or suffering from gastro-intestinal symptoms, chronic constipation is a very common premonitory symptom of Parkinson’s if you’re seeing a tremor at rest, it is time to get to the doctor because at that point it said that you may have already lost 50 and 80% of your dopamine-producing cells. But, folks, it is possible to make this diagnosis. Some tests can be done. A lot of people come to me saying the doctor just looked at me and said, You have Parkinson’s. I just didn’t get much of an explanation as to why you weren’t going to do any tests. I saw one of those patients today who said we are and we do scan, punch, and biopsy. If you guys are going to get to hear from Dr. Todd Levine from CND Life Sciences, talking about that new technology, at any rate, we get the diagnosis, and then the next step is that I’m going to come to see Dr. Haase. What does it look like if I come to your clinic? Can you take me through that experience of evaluation? Then you say, I think the treatment for you is therapeutic plasma exchange, and what can I expect?

David Haase, MD

Sure.  We typically start with individuals doing a consult via Zoom as an educational consult concerning whether this is a good fit. Because a lot of our patients come from a great distance, we don’t want to inconvenience anybody or have them incur additional expenses if it would not be a good fit. We started in that direction. But when you walk into our clinic, one of the first things you’ll see is a massive wallpaper of the entire metabolic map of the human body. It can be; you’d love it. You come in. It’s a true nerd; it’s a true nerd in the hospitality area. I have to tell you this. then and then we have photos of the Kinect dome with various brains on the wall as well. It’s true when people walk in to get this feeling that the metabolic map is all that all the chemicals that are in the body, and it’s wonderful; it at once puts one in a state of awe of, wow, how fearfully, wonderfully, and complexly were made, and how many things it puts on, but a lot of all about how many things, how many things must be going right, how many backup systems we have, and how complex biology is. It’s just a wonderful thing. 

But sorry, when you ask that question, I was just imagining somebody walking into our lobby because they stand and look at the wall, and they’re like, “What is this?” Oh, so, but when somebody wants to, I was trying to think, Okay, I’m having memory issues or I have some identified disease, and I want to investigate plasma exchange. We’re thinking about their likelihood of benefit, and because the evaluation is for you to understand how old you are as individuals who are very early in their aging process, they say 40 to 50 are probably not going to get as much benefit as we believe. Let me take you back here. Because of some of the research that we’re doing, I’m investigating the effect of plasma exchange on longevity itself. I’m working with a silicon-based biotech company. We’re doing it; we just completed our data acquisition, and we ran a study of individuals who got different amounts of plasma exchange at different frequencies. and we did an incredible amount of studies on these people, looking at their metabolome, their proteome, their transcriptome, their methylation, all of these millions and millions of markers. We’re tracking exactly what happens over time to these individuals about their biology. We can’t say a lot about the information coming out of that thus far, but in general, we know that the sicker an individual is with other conditions, the more vascular disease they have, and if they have more autoimmune disease, they’re more likely to benefit from plasma exchange, we believe, because we’re seeing more degeneration than regeneration. I think one of the useful tests to do to say how much benefit there may be is that true diagnostics has a test that measures a biological cycle age. And so it’s called the true age test. They take a look at about 900,000 different pieces of DNA, and is there a single carbon added to a methyl group added to those areas? Through a very large database, they can assess, like, how biologically old is this individual. We think people who have an accelerated biological age have a greater likelihood of benefiting from plasma exchange. When we do this test on individuals, we can see as much as a six-year drop in their biological age from one plasma exchange now, and so one of my deep fascination with this whole field is why does this work? So that’s the reason for this very large study. What are the markers that are moving when we’re doing plasma exchange? Who could both benefit? But right now, I’ll tell you, if you have an excess of birthdays, you’ve got the potential for benefit. We have to start looking at aging as a disease. If we’re taking this seriously and we’re thinking, I get it now: aging is probably the most important disease for us to look at because all these other diseases are co-morbid with it. Then, if we have an intervention that is effective in changing the course of aging itself, those would be indications of the challenge. That’s a basic thought pattern there.

Kenneth Sharlin, MD

Well, you’ve got me pretty excited about it, and I know the other listeners are very excited as well, which brings us toward the end of our interview, and we want to know how we can connect with you. How do we get access to this wonderful therapy and all the services that your clinic has to offer?

David Haase, MD

Oh, well, I just go to maxwellclinic.com. There’s all kinds of information on there, things you can learn more about what we do, and if you’re interested in plasma exchange and if that’s important to you, we can set up a consultation and speak with one of our clinicians and go from there. But it’s because I said this in our time before we were in the film. I don’t understand how doctors can get proud or why there’s something to humble us in medicine. Sometimes it is such a privilege to get to walk with people through their challenges, to listen, and to learn. It is an amazing thing. One of the things we try to do well here at Maxwell Clinic is to listen because we’re not just treating diseases; we’re walking with humans on their life journey. Nobody gets out alive. But we do want to have the very best days that we possibly can while we’re here.

Kenneth Sharlin, MD

While I won’t tell that Silicon Valley executive who came to see you and said, I want to live forever, that we haven’t quite solved that one.

David Haase, MD

Oh, yes. No, we’re not close. No, we’re not there yet. But it’s a lot.

Kenneth Sharlin, MD

Much can be done.

David Haase, MD

Wow, so many things are on the horizon here that we’re going to better understand aging, and we’re going to start to recognize it as a mechanism. It is a mechanism. I think that’s a useful thing, like an infection. We should think of aging as almost like carrying an infectious disease or a toxin. All right. How can we have less of a burden from the mechanism of aging?

Kenneth Sharlin, MD

What we do as functional medicine doctors—sometimes I tell my patients—the operative word here is function. It’s not that we’re necessarily going to live forever, but we want to make every day, every week, every month, and every year the best that it can be. Too often, we go to the regular doctor. They’re not changing the trajectory. Not very much at all. They give us a pill. Yet, how many times do you show up in the emergency room with a stroke already on aspirin? Are you already on blood pressure medicine for your diabetes pill and things like that? If you want to see a change, if you want to be the best version of yourself, then maybe a visit to the Maxwell Clinic to have treatment with Dr. Haase and his team, potentially including therapeutic plasma exchange, would be a great direction to go.

David Haase, MD

Thanks, Dr. Sharlin. Thanks for having me on.

Kenneth Sharlin, MD

It’s a pleasure to visit with you. It’s been all too long. Bye bye.