S5E25 HSCT with Professor Richard Burt

05:12 “In a randomised trial, [HSCT] was just hands down much better than any [other] drug. All the drugs you use for MS are based on approval for slowing disease activity. That is slowing the number of relapses or slowing the rate of progression of disability but not stopping it or not reversing it. Often you stay on these drugs indefinitely. A transplant, on the other hand, is a one-time treatment and afterwards, you get better, your neurologic disability reverses, nothing else had done that.”

14:02 “MS causes accelerated loss of brain volume, that is brain atrophy. Unfortunately, as we age, we get brain atrophy and a normal, very low, but normal decline. But once you get MS, that decline takes a much sharper drop, and you’re losing neural function a lot faster than normal ageing. For some reason, that’s not viewed as a sub-acute or semi-emergency situation that you want to reverse. Traditional drugs have mostly just slowed that rate of decline, but it’s still faster than what happens with normal ageing. I would think a more aggressive approach up front would be wise, but you always have to remember [the] risk–benefit. If we could do a stem cell transplant with zero risk of mortality, I would say absolutely for everybody. But you can’t do that right now.”

34:20 “There are 80 different autoimmune diseases that I can think of offhand. They’re all “homeless” in different departments like Crohn’s disease [which is] in gastroenterology, Scleroderma [which] is in rheumatology, and multiple sclerosis [which] is in neurology. They’re all separated [into] different areas. If there was a better organisation, beginning at a federal level with a national institute of autoimmune diseases that supports centres of excellence around the country, that would really help this go forward.”

Want to learn more about living a full and happy life with multiple sclerosis?  Sign up to our newsletter to hear our latest tips.

Overcoming MS  00:01

Welcome to Living well with MS. This podcast comes to you from Overcoming MS, the world’s leading multiple sclerosis healthy lifestyle charity, which helps people live a full and healthy life through the Overcoming MS program. We interview a range of experts and people with multiple sclerosis. Please remember, all opinions expressed are their own. If you are able to, we would be grateful if you could donate to help support the podcast and other work of Overcoming MS to help give hope to those impacted by multiple sclerosis. And now here’s your host, Geoff Allix.

Geoff Allix  00:38

Welcome to the latest episode of Living Well with MS. And I’m very glad to have joining me on this episode Professor Richard Burt. Professor Burt is probably one out not probably definitely the most accomplished scholar and personal person at any time that we’ve had on this podcast he’s a Fulbright scholar. He I’m going to read this all out because I will miss things otherwise, Fulbright Scholar, professor of medicine at Scripps, professor at Northwestern University, the CEO of Genani, I believe. He is the pioneer in the field of HSCT. What else we got he’s the America’s first use of HSCT for MS amongst many other things including Lupus, Crohn’s Disease, he led the world’s first randomized trials for HSCT for for MS for scleroderma, and I think the the last point which was terrifying get this absolutely correct, is particularly impressive, which is having to turn out my page, which is in the Scientific American journal. He was listed as one of the top 50 individuals in the world in improving humanity. So no caveats not in MS. Not in medicine, but literally one of the top 50 individuals in the entire world and improving humanity alongside people like Bill Gates. You know, there’s a list of people that are very familiar. So a an incredible bio, compared to everyone we’ve had. And I would very much like to welcome Richard Burt to the podcast.

Richard Burt  02:33

Thank you very much.

Geoff Allix  02:35

So that was a brief bio, because you’ve given me a long, long list, it might take up the entire thing. So you do have an incredible list of accomplishments. But in your own words, could you introduce yourself and talk a bit about your work with patients with autoimmune conditions in general, and with this podcast in mind, MS in particular?

Richard Burt  02:58

Right, so I’m a professor, and I’m a physician and MD and I’m a pioneer in the use of stem cells for autoimmune diseases. I’m really known for my work in hematopoietic stem cell transplant that is using the blood stem cell hematopoietic means blood. But I also have been working steadily with IPS and we have certain patents in that and in the future, hopefully, if time allows, we’ll be developing some induced pluripotent stem cell, our IPS therapies as well. But the therapies that we have done and we’ve published and we offer it for patients now, and then I’ve helped teach universities around the world how to do and they have trials now to do it is hematopoietic stem cell transplant for autoimmune diseases. And that was an idea occurred to me about 35 years ago, I was a young fellow at Johns Hopkins. And so they were re-immunizing patients for all their childhood vaccines after a stem cell blood or hematopoietic stem cell transplant for cancers. And the reason they were doing that is they lost their memory, immune cells, their memory response to those vaccines. And so it occurred to me that’s exactly what you want to try in an autoimmune disease. And I said that to my professor at the time because I used to follow, I said, you’re re immunizing these patients. He didn’t respond, I said, that means they lost their memory in response to those peptides that those little proteins. He didn’t respond. He wasn’t being rude, just really busy clinic and then I said, that means we could use this technique for autoimmune diseases. And he stopped, looked up at me eyes, appearing above his glasses and said, You’re right, we could do this for multiple sclerosis. So that’s how it started and then began 10 years of preclinical animal work in animal models about immune diseases, including MS. And when I first started it, I didn’t even know there were animal models for MS but there are and after learning how it works and those systems and studying the immune system with that approach, we eventually were able, or I was able to get approval to do it in patients. And so that eventually led to phase one, phase two, phase three trials, phase one is just a small trial for safety. Phase two is more larger number of patients for efficacy. And phase three is where you compare it to what’s out there, that is a disease modifying therapy. And along the way, we had to learn how to tweak the trial, that conditioning regimen used to make it most optimal, learn the best type of patients that respond to this. And then in a randomized trial, it was just hands down much better than any drug. So you know, all the drugs you use for MS they’re based on approval for slowing disease activity that is slowing the number of relapses, or slowing the rate of progression of disability but not stopping it or not reversing it. Often you stay on these drugs, so kind of indefinitely. So a transplant, on the other hand, it was a one time treatment. And afterwards, you got nothing and you got better your neurologic disability reverse, nothing else had done that. And you didn’t need any more treatment. And we reported results up to five years. And importantly, quality of life improved, which doesn’t happen on these drugs. And the reason it doesn’t happen on the drugs people take for MS is it doesn’t reverse the disease, it just slows progression. And then you’re having to deal with the side effects of the drugs and taking them and inconveniences and money, time, expense involved in that quality of life doesn’t improve. Whereas after transplant, you’re drug free, and you get better. And most people, the majority stay improved. And so I knew that the majority about 75% to 78% did not relapse in 5 years. But most recently, I wanted to get this information out to the lay public. Because a lot of people still don’t know this. I mean, this is a hard fought work over decades. And it fundamentally changes this disease from chronic process to one time reversible illness. And so but people don’t know, so I wrote a book Everyday Miracles. And that’s how this interview came about. And this is the book that you can get on Amazon, it’s available. And it’s written for the layperson. And I if I use a bigger word or medical term, I explain it, I think medical people will also enjoy this, anybody in the medical field, anybody with MS, anybody with autoimmune disease, or just any person I think, would really enjoy this book, it gives you a look inside these diseases and what it does to people in this therapy and what happens to them after that treatment. In fact, this book, I almost called it Profiles in Courage, because it’s stories of patients and what MS was doing to them on these drugs, and then what happened to them after transplant. And you know, it’s really, I think, uplifting to see the courage, the determination of the human spirit, when they’re told they have a chronic disease that they’re never gonna get better from, they’re just slowly getting worse, and how they fight and keep looking for an answer, how they have to, or the, the victim of domestic abuse by their own immune system against their own body. And then how transplant turns this around, because it resets the immune system, to a new immune system tolerant to self. And so in writing this book I started calling texting patients had done 20, 15, 10 years ago, just randomly for their stories, and I found out my gosh, they’re still in remission, no drugs, got better, stayed better, having great lives, most of them, some still have some permanent, permanent deficits, because that some damage can no longer be reversed. It’s stunning if you get them, right that you can still reverse damage and not just stop inflammation and stop attack on the immune system. But actually on the neural system, that central nervous system, not immune system, the attack by the immune system on the central nervous system, and you can stop it, but they can actually repair itself to some extent. And so I was surprised that every single one I contacted was still in remission. And obviously people are glad to be free of the medical system and, you know, no particular interests come back at another MRI and go through a big exam and all that. But they’re doing so well I thought I should if I ever find the time systematically make a report of everybody beyond 10 years and how they’re doing because we know now that most of the relapses do occur within the first five years and that by five years 75% to 78% remain in remission without ever having relapse ever needing new drugs. And that it seems like the majority after that stay in remission. Because we, you know, we always tell people to contact us if they have a relapse, I only have one contact after five years, that was about 11 years out. So just randomly calling and found out, wow, they’re still doing great. And so some of their stories are in here. And the main reason for doing this is that, despite all my talks in medical publications, and writing medical textbooks, a lot of physicians don’t know this. And a lot of patients don’t. So I wanted to empower the patient. So they could read it, they could go to their local physician saying what about this? And, of course, a physician could look at that say, well, that’s a lay book. That’s part of the science fiction. It’s not, it’s not fiction. And so one year ago, in November of 2021, I came out, I was the senior editor on this textbook ton of work, rewriting chapters working with authors writing my own. And it’s 686 pages, and 140 professors and associate professors from around the world, including England and Europe, mainland Europe. China, Australia,

Geoff Allix  11:16

Could you give us the name of that with people who are just listening?

Richard Burt  11:19

Yeah, so this book is called Metabolic Stem Cell Transplantation and Cellular Therapies for Autoimmune Disease. It’s also on Amazon. It’s a medical textbook. So unfortunately, it’s expensive compared to a lay book. It’s designed for physicians and researchers in the field. So most people may find it a little boring, that are not doing this type of research, or who are not working with these kinds of patients or who are not directly doing cellular therapies. But I’ve often found a lot of my patients have spent a lot of time reading and studying and figuring out these diseases, and they know a lot. And I think they’ll glean information out of those chapters for their given diseases as well.

Geoff Allix  12:03

Are you aware of Gavin Giovannoni in the UK. So he’s, he’s very much at the moment talking about what he calls flipping the pyramid where, where traditionally, we would go with an approach where you start with the mildest form of disease modifying therapy. And then as you get worse, you move up to something more efficacious. And eventually, you might well be have lost complete mobility before you’re offered something like HSCT. Or, and what he’s saying now is actually why are we not offering as first line of defense immediately upon diagnosis? Why are we not offering HSCT or Alemtuzamab, he said, one of those two things should be offered to everyone, as their first at least as a choice, they should be given the choice to say, not starting you with something very mild and very, yeah, okay, as less no side effects, but also, they’re not as strong drugs, and you will have progression. And then, you know, ultimately, somebody perhaps that you find that, of course, but then equally, a lot of people are, are accumulating disability before they’re offered the strongest treatments. And is that something you agree with? It actually should be flipping it and saying, actually, this should be offered first? not last?

Richard Burt  13:32

Yes, I mean, I definitely have listened to his lectures, been the audience. He’s listened to my lectures. I do like the way he thinks I do like the way he’s trying to adjust the thinking and the field of neurology. And certainly one of the concepts that has been missed, I think, in the field in terms of this disease is a concept of brain atrophy. You know, we all know heart attack that time is cardiac tissue, and you have to work fast to save the heart is viewed as an emergency. And on the other hand, MS causes accelerated loss of brain volume that is brain atrophy. Now, unfortunately, as we age, we get brain atrophy and a normal, very low, but normal decline. But once you get MS, that decline, takes a much sharper drop, and so you’re losing neural function a lot faster than normal aging. And for some reason, that’s not viewed as a sub acute or semi emergency situation that you want to reverse that traditional drugs have mostly just kind of slow that rate of decline, but it’s still faster than what happens with normal aging. So I would think a more aggressive approach up front would be wise but you always have to remember risk benefit and you know, if we could do a stem cell transplant with zero risk of mortality, I would say absolutely for everybody. But you can’t do that right now the lowest mortality for the procedure is 0.5%, in my own hands, and we published the results of 507 patients in the journal, Neurology, I think, about a year ago, and the mortality was 0.5%. So, you know, you never want anyone to die from your treatment. Of course, I think you give all the options to the patients and let them make that decision. But you want it as safe as possible. But obviously, there are some types of MS that are so benign and so slow, and never really get to progressive form that I would not offer this to. On the other hand, the vast majority of patients with MS have been undertreated and have been allowed to get into progressive neurodegeneration, which is no longer an immune mediated immunologic attack on the brain, but a neurodegenerative disease for which nothing works, including an hematopoietic stem cell transplant. So you don’t want the patients to get there. You don’t want this under treatment that has been going on in the medical community for this disease. So it’s refreshing for me to hear a neurologist speak as Professor Gavin does, at Bart’s

Geoff Allix  16:27

I think we’ve covered the benefits. And so you’d say that the primary risk of HSCT is essentially like a one in 200 risk of fatality. And other than that, is there other risks?

Richard Burt  16:42

Well, it’s about one in 500, now, here’s another big caveat. When we talk about disease modifying therapy, there’s all these drugs out there 13, 14 drugs, there seems to be a new drug appearing all the time but, and that’s good, because all drugs have different side effects. And, you know, if one’s not working and physician can change to another, they just have more tools in their armamentarium to treat the disease. But when you talk about toxicity and efficacy, you have to be disease specific. For instance, there’s one drug that’s very high risk compared to all the others of giving a brain infection with a virus called JC virus and that gives PML, which, if it doesn’t kill you leaves you much worse off so you definitely don’t want that but the drug that can do that is an ad Elizabeth, also known as a Tysabri. It’s occurred with some of the other drugs but nowhere near Natalizumab when you use Natalizumab and you need to check if a patient is JC virus positive, most are and then you need to follow the index and if it’s rising, you need to stop the drug before they get PML. You don’t need to do that when you’re on Gilenya or Copaxone or anything like that. But you definitely do when you’re on Natalizumab. And the problem with HSCT people think it’s just one thing out you’ve got all these drugs, they got HSCT no HSCT they’re toxicities and their efficacies vary not only by patient selection, but by the most importantly the regimen you use, which is about five days of a conditioning regimen to knock down your immune system and then allow the stem cells to regenerate a new one. And that regimen you use determines the toxicity both early and late. And so it’s very much regimen specific what you have to worry about in terms of toxicity within so don’t think of HSCT as one entity. It’s there’s different ones and within HSCT. There’s two big subdivisions one’s myeloablative. The others nonmyeloablative. Myeloablative means if you don’t give the stem cells that you collect from the blood or bone marrow, but bone marrow is the way it was done in the old days. Now we get them out of the blood, we get the bone marrow stem cell or the blood stem cell out of the blood these days, not out of the bone marrow initially it was out of the bone marrow. So it’s traditionally called bone marrow transplant but that’s not done very often. It’s peripheral blood transplant now, but now but in any event, if when you do myeloablative regimen which are used in cancer, if you don’t give those stem cells back the patient is going to die. Because the stem cells the bone marrow are all killed and your can’t live without the bone marrow making cells because it not only makes your immune cells that fight infection it makes your blood cells to carry oxygen, it makes platelets, clot Bloods and you know, you just have to die without those things. So you have to give the stem cells back to allow that recovery on a nonmyeloablative you don’t have to give them back because the stem cell compartment is not damaged by the drugs you give only the immune cells are so it’s more focused to the cells causing the problem. And but if you give them back in a nonmyeloablative you shorten a period of neutropenia and needing blood transfusions by about four days. So anything that shortens being in the hospital or shortens the risk when you could get an infection because you don’t don’t have a good number of cells to fight them, or have a serious bleed because your platelets that clot blood or too low or red blood cells to or whatever, anything assurance that that’s good and that’s why they’re given but if you don’t give them you’re still going to recover just fine but about four days longer. So that’s the big difference within transplant. So myeloablative nonmyeloablative, then within those, there are different regimens being used with different toxicities. For instance, you can make a nonmyeloablative more immuneablative than any myeloablative regiment out there just but still immune specific ones damaged stem cell compartment. So the details are important. And it kind of goes beyond I think the audience listening to this except to know, there are different types of transplants, and that one way of breaking them down. And important first breakdown is whether they’re myeloablative, that is cancer regimens, or nonmyeloablative, which are immune specific for the immune system, I’ve always been an advocate for nonmyeloablative don’t use those cancer regimens and much more toxic, they’re much more expensive, about twice as expensive. For an expensive procedure to begin with. In America, now the costs in Britain are totally different than in America, because in the National Health Service, you know, they don’t include the cost of the room and the hospital security guard.

Geoff Allix  21:18

In the UK, it’s it wouldn’t cost you anything, it would be completely free. But if you are offered it, yeah, this is the thing. So it’s yes. If it’s available to you, then it’s free. If it’s not, then it could be very expensive.

Richard Burt  21:33

So in other words, a transplant in America, but nonmyeloablative the way I do it’s $100,000. In the UK, it was about $40,000 That is like why is that and then I realized the it’s because because I’ve written a paper on that. And I did it with people with a university in England. And it’s because in their system, they’re only counting the drugs and the nursing and the physicians, they’re not counting the infrastructure, because that’s paid for by the National Health Service, and they don’t have access to that budget. So they don’t count that but in America, you know, all that has to be paid for out of the cost that the patient or insurance pays. So the prices are really the same. It’s just the bookkeeping is different. But in the NHS, somebody’s still paying for it. So you know, it’s just the way the accounting done is different. But the costs are about the same. It’s really $100,000 overall society, patient insurance, whatever. However, the bookkeeping is done, it’s different in America than in the UK. But my myeloablative regimen is about $200 or $250,000. So it’s more than double the cost. And it’s more toxic. And I don’t believe they’re, in fact, any better. Now, you can’t prove what I’m saying, without doing a randomized trial between the two of them, but nobody’s going to do it. I certainly wouldn’t. Because our results are so good, with a less toxic regimen that I don’t want to use the more toxic regimens designed for cancer. And again, the reason they’re designed for cancer is you want to kill the Leukemia, the malignant stem cell in autoimmune disease your stem cell is not bad, it differential to immune cells that become mis directed later in life and become aberrant or bad. Now, there’s a rare exception, there’s certain childhood immune diseases that are a genetic defect of the stem cell. And you’d have to do an allogeneic transplant for them not autologous. But those are rare. And in fact, in the medical textbook, we have a chapter on those genetic immune diseases that are almost always picked up in children. But that’s not what the large number of autoimmune diseases are, especially in adults, like MS. They’re not pre programmed to occur. Due to a mono genetic abnormality. There’s probably an impact of multiple genes and environment and hormones that trip your immune system, but it’s not purely genetic. And it can be reset with an autologous transplant, and there is no need to destroy the stem cell compartment like you do in cancer. There’s no rationale to do it. In fact, the stem cells are not bad.

Geoff Allix  24:13

So you’ve mentioned about the ability to have the right patients. So you’ve said that you need to have people who are in the relapsing phase of MS. Are there other caveats that you’d say that people who make a good candidate for HSCT is it younger people and fitter people, is it fairly broad within that spectrum?

Richard Burt  24:36

I would say younger people do better than older. I think that’s pretty much true with any type of therapy. And it’s true in transplant, but the key is that they’re relapsing remitting. And again, if you just have one attack every 10 years and you’re walking around, you’re fine. I wouldn’t do this. There’s benefit’s not there for it. So back to your question about doing it for everybody. No, but the people we look for people who’d have at diagnosis, so much activity of MS in the brain at onset that a neurologist would want to start one of these more potent immunosuppressive drugs like Cladribine or Lemtrada, or Ocrevus. That’s a group I would take to transplant upfront. Otherwise, I would take people who were started on a first generation DMT, like, Copaxone, interferon who have been two attacks or more in the last year, or a group that’s on a second or third generation DMT, like Gilenya and Tecfidera, or, you know, even Ocrevus or whatever, or Natulizumab who have one attack within the last year despite being on those drugs. And those are the people with relapsing remitting, who do very well, and they do well, independent of age, the oldest we did was age 58. And that person did well with improvement. But I think the younger you are, the better. And it’s just the body’s able to recover faster. So that now I wouldn’t do secondary progressive. That’s a neurodegenerative process. But again, the caveat is, you’re not one day relapsing remitting and the next day secondary progressive, there’s a gradual transition, usually over years. And you don’t know when it really occurred when you’re there, you know, secondary progressive, but you don’t know when it really happened. And you could see a patient every month for two years and not know it happened, then all of a sudden look back to you know, two years ago. And yeah, this is secondary progressive. So what happens in that gradual transition, is secondary progressive means that your baseline, your neurologic baseline is declining, you’re getting worse. But you’re not, it doesn’t correlate with any new attacks on the brain, no lesions, no new acute attacks. But there’s a transition period where you have active secondary progressive, where you’re progressing between it getting worse, declining between acute attacks, but you still occasionally have an acute attack. So active secondary progressive is a new MRI lesion enhancement or new acute attack within the last year, despite being secondary progressive, that group we can still benefit from this, not as much. So instead of like a one to 1.5 improvement, in EDSS, which is how you measure neurologic dysfunction, or neurologic ability is zero to 10. That’s a scale 10 is dead, zero is normal. So it gets better by one one and a half points. With active secondary progressive gets better by 0.5. Half a point, but at least still gets better once you’re not active. It no, it doesn’t help you anymore. Now the argument can be vague, well, maybe you plateau out. But you know, I think once you’re in non active, secondary progressive, you really need to be looking at a whole different approach, not an approach that resets the immune system, because it’s no longer in the immediate it is neurodegenerative. Now what you need is a true neuro degenerative therapy of some kind, or, for instance, a neuro regenerative stem cell type of therapies that currently don’t exist. So we don’t take non active or late secondary progressive patients through this procedure. And if you have relapsing meaning, but it’s fairly mild, and you don’t have many attacks, and you’re not acute, you’re not having severe attacks. It’s very infrequent, I wouldn’t do it. I think the risk benefit justifies it. But I think definitely there’s a large group of patients with relapsing remitting, which is 90% of patients at diagnosis that would benefit from this being offered much sooner than what is currently being offered. Now, why isn’t it being offered sooner? And it’s not that physicians or neurologists don’t want the best for the patient, they all do. They’re all very hard working, they’re all very intelligent, and they all have a ton of experience. The difference is that it’s the way medicine has gotten set up. And I go into that in the last chapter in my book, and we won’t have enough time to go into all of those. why that is. It’s not that any one particular person or group of people is malevolent. Absolutely not. It’s the structure of medicine that has directed us down certain silos. So for instance, neurologists do not understand what stem cell transplant is, to them is just these awful cancer regimens and the suffering of a cancer patient, they don’t do it. They don’t live it, they don’t see it, you know, it’s kind of like that movie. Avatar, where, you know, they said, “I see you” meaning you understand each other, they don’t see it, because they don’t live it at all. And you know, so to them, they’re not going to refer patients to it unless they’re late secondary progressive when it’s not going to work. The hematologists that do transplant don’t understand the MS. Even the difference between a mile ablative and a nonmyeloablative. And the rationale for it they don’t because they use, won’t there’s no, there’s no such thing as a nonmyeloablative, autologous transplant for cancer. They’re all myeloablative for cancer. So they, they don’t understand the disease. And they haven’t subspecialized in it. And so I think that’s the big hindrance to why this isn’t going forward. There are others, and they’re listed in the book. But what made me accomplish it, and to be able to understand it is that I, as you mentioned, I had this idea to do, I got that because of the gene therapy study I did in leukemia, but I got this idea to do this in autoimmune diseases. 30-35 years ago, I started working in animal models on it, I found that it would work, I learned a lot about the immune system. So I totally shifted my focus, I stopped doing leukemia and Cancer totally. And I focus on immune disease back before anybody had ever done that. Now, that’s a risky move, you could end up unemployed.  You’re doing something nobody’s ever done. There’s no, there’s no path to follow through, but ever, but I did it. And by doing that, by focusing on that, by giving up cancer, I became really good at what I did, and was able to accomplish a lot and see this field expand.

Geoff Allix  31:16

So do you see a future where there’s actually auto-immunologists, who crossed the more traditional, if you like hematologist and neurologist, and that they actually will understand the whole picture.

Richard Burt  31:31

Yeah, well, so I think that’s, that’s one of the key reasons I was able to cross that field because I focused on it. And I think a lot of people think you should kind of be good at everything. But the truth is kind of one of the little secrets, I think out there, if you really want to be good at something, you have to really sub specialize and take that risk, like Federal Express, became very good world famous, but they focused on only delivering packages. They didn’t compete with US Post Office on envelopes or letters, they focused on just packages, Subway sandwiches, focused on just making Subway sandwiches, kind of a crazy idea, but they have stores around the world. Pizza Hut focused started one little guy out of college stopped going to classes started making pizza, they focus on one thing making pizzas. And then they spread around the world. So when you do focus on one thing like that, you get really good. If you don’t you get pulled in other directions. But in any event, I call that in the book homeless. So one of the ways around that homelessness is you can take someone that knows transplant, and they focus on just MS or just autoimmune diseases. But even then there’s so many of those, and I’ve mentioned five of them in the book, and they’re different. And you have to understand each one differently, that you know, you’d have to focus on just a few, or you take a neurologist and focus just on transplant for MS, very few people will do that very, very few. They see that as a risky proposition up front. So I think you know, a few will know as time more and more probably will because it does work and patients are going to demand it and that’s the difference. But in the book, I say, you know, I’m kind of homeless. And this is a homeless field. And one of the ways around that is through national directives in America, there is no national institute of autoimmune diseases. There never has been there’s a National Cancer Institute for Cancer. And it funds cancer centers all around the country, and it focuses people in cancer. But there’s no national institute of autoimmune diseases that would fund autoimmune Institutes around the country in which stem cell transplant and other types of cellular therapies and believe me, other types of cellular therapies can also be involved in treating patients with autoimmune diseases, whether they’re neuro stem cells, IPS induced pluripotent stem cells, like I also work in or car T cells or mesenchymal stem cells or whatever, there’s going to be other types of cellular therapies. So if you had these national institutes of autoimmune disease centers that funded through NIH or through the National Health Service in England, for centers of excellence, just like you have in cancer, but that they included a department or division of stem cell transplant or cellular therapies, this would really take off. And so there’s like, oh, I don’t know 80 different autoimmune diseases that I can think of offhand. I have a table in the book of 75 of these different diseases. They’re all, you know, homeless in different departments like Crohn’s disease, and I talk about transplant and here that’s in gastroenterology. scleroderma is in rheumatology, and multiple sclerosis is in neurology. They’re all separated out in different areas. So, you know, if if there was a better organization, you know, beginning at a federal level with the National Institute of autoimmune diseases that supports centers of excellence around the country that would really help this go forward. Short of that. I have no power over legislative bodies anywhere much less than Washington DC. You know, maybe they’ll read this book and start getting some ideas. But the short of that it’s going to take physicians making that crossover and someone who knows transplant focusing in on one or two or a few autoimmune diseases and making a career out of it. And believe me, they’ll make a good academic career with a lot of publications. Because they’ll become experts in doing it just like I did. And so that’s kind of where it’s going right now. But there there are other ways to accomplish this. But that would require kind of a restructuring of medicine. And the reason in roses way is that medicine arose by people specializing on what they could see. So if you saw the skin, you really wanted to work on that you became a dermatologist, the eyes ophthalmologist and in autopsies when we saw the heart and it was figured out how circulation works, you know, that was no small feat, but then you became cardiologists, you know, you became pulmonologist lung doctors, hepatologist, liver doctors, you can see these organs. But for the longest time, nobody had a microscope, nobody could see the cells in the blood. And then once they got them, they didn’t know what these cells did that was eventually sorted out by the time that happened. Departments of immunology that did the basic research on these immune cells, but they didn’t treat any patients because the treatment of patients was already orphaned off into these all these different departments, you know, depending on organ involved, so MS ended up with neurology, so there was never an immune treatment Institute. So you know, they’re they’re basically two ways around this one, you start national funding Centers of Excellence for institutes of autoimmune disease. The other is that people who know how to do transplants, give up doing cancers give up thinking myeloablative, learn these diseases, MS. Neuromyelitis optica, scleroderma, Crohn’s, whatever, learn these diseases, and read the literature, what’s already been accomplished, and who, you know, it’s already well defined in some of these diseases, the optimal patients to select an optimal regimens and then start doing it. And there’s, you know, many, many more autoimmune diseases that individuals could focus on and perfect this therapy and, and bring it to the bedside. So it’s going to be up to really, I think young physicians that are willing to take that initial leap forward to focus a little bit untraditionally to offer this great therapy by patients driving it bottom up, you know, that’ll happen, they’ll push doctors to do that. And it’ll initially probably be a doctor that does leukemia, or transplants, or lymphoma transplants, who starts doing MS and then realizes, wow, you know, he can his whole career can be tied up just doing MS. They’ll focus on it and become very much of an expert. So that’s kind of, I think, the way it’s heading short of changes in directors at the national levels from governments.

Geoff Allix  38:10

If we’ve got individuals who are listening to this, you think well, that is perfect for me. They’ve completely fit within what we’re saying that relapsing remitting their young, they’ve got active MS. And they’re interested in this, okay, what would they look for in a clinic or physician to to give them more information and to take it further in looking to get HSCT?

Richard Burt  38:37

I set up an educational website as well. I’d recommend get this book and read it. Everyday Miracles, people are listening. Yeah, by Richard Burt, by the way, the forward is by the Dalai Lama. I was very blessed to have that. Yeah, I also set up a website is called astemcelljourney.com. Lots of information there, tons of information, All my publications are there, you can download and read them. You know, I don’t put anybody else’s there, that wouldn’t be appropriate. But mine are there as well as talks and rationale and many.

Geoff Allix  39:12

We’ll put links in the show notes as well.

Richard Burt  39:17

Look at at what centers are doing this in America, I do it at Scripps, in La Jolla, California. And you can contact us there and we’ll start the process of a nurse contacting you for Intake Forms, evaluation to get the necessary information. Because if it’s clear that you’re not a candidate, you’re late secondary progressive will just screen you out so you don’t have to waste time or money to fly there to be evaluated. So or you know, in the UK, they’ve now started a protocol called Star MS, which offers transplants versus one of these aggressive, new MS drugs. I think, you know, Cladrabine or Lemtrada, or Ocralizumab or something like that versus transplant. So that’s, ongoing in the UK right now. You know, it’s a trial, you get randomized one or the other. At my center, because we already completed a randomized trial in transplant was markedly superior, we’re offering, still a randomized trial, but two types of transplant the way I’ve always done it versus a way that I think, even safer. And if we get this same long term benefit, it would allow it not it would be cheaper, and it would be safe enough for us to do it as an outpatient. So you don’t even need to be in the hospital, which would then markedly the cost, because most of the cost is the overhead of being in a hospital. You know, like what you don’t see in the UK because those costs are hidden paid for by the National Health Service. But in America insurance has to pay for it is a hospital room’s like $2,000 a day, I mean, it’s crazy, you could have a great hotel suite for that. And that’s certainly not what you get. But that’s what they cost because of the expense and overhead, the bureaucratic red tape and all the stuff they have to do and documentation and oversight and stuff. That’s just the room, you know, you put an IV in just hang bring an IV pole and there’s another $200 day, every IV bag, it’s like another $500 a day it gets really expensive. So you know if we can do it as an outpatient or markedly undercut the cost even more. And so that’s what I’m comparing, the way I’ve always done into another nonmyeloablative regimen that I know it’s going to work upfront, will it give us good long term results? If it does, it’ll be cheaper to allow us to do this as an outpatient, which not only is it just cheaper being done in house, less expensive, it’ll be even much cheaper because it can be done as an outpatient.

Geoff Allix  41:47

Even if you’re talking about the, let’s say, $100,000 that you mentioned before, even at that level, would you say because I’m aware that I saw I’ve gone through starting with Tecfidera and then ultimately had Lemtrada infusions. And I’m aware that actually the Lemtrada was expensive, but ultimately, may well have been cheaper than the Tecfidera in the long run, because that I was going to take for the rest of my life, which hopefully it was going to be a long time. So how does it compare when you say actually well, $100,000 once. How does that compare to somebody say like in their say they’re in their 30s and they’re gonna live a long time. Yeah,

Richard Burt  42:31

so I actually put in the book a table of the cost of all these drugs when they first hit the market like the interference, Copaxone first hit the market in 1994. And the 2020 costs. So when they hit the market, they were $9000 a year, or $12,000 a year. In 2020, they were $100,000 a year. So what happened, there’s like I listed a table 14 drugs and what their initial cost was when they were first FDA approved that year, and then what they are in 2020. And I’m sure they’re much more now, but because they’re they hyper accelerate much faster than the rate of inflation in their charges. And what happened is a new drug comes out, it’s more expensive, because cost development and regulation, everything’s much more expensive. The old drugs just match the price of the new one. And so they all run all around $100,000 a year, which is the cost of one transplant, but transplant’s a one time thing. So you know, if you start looking at this over five years where 75%, don’t relapse or need any new drugs, you’re saving $400,000 in three quarters of those patients. over that five year interval, it’s a big cost savings to society insurance. But people don’t recognize that one of the reasons they don’t is another problem I bring up at the last chapter and I titled it financial toxicity. And that is physicians are not aware of the cost of things. Your physicians in the UK are not because their employees of a public system. In America most of them aren’t because you’re not taught it. Your publications, whether it’s Lancet or New England Journal or whatever, they never list cost effectiveness or the costs of this stuff. You don’t know what it is. And unfortunately in America, more and more physicians are becoming employees of hospitals or institutions and the bureaucracy and the business people have pushed them to build more and more and more. And they expect you to do so many for the salary you’re getting. And if you don’t achieve that you’re penalized because you know, they don’t feel they’re getting their value out of you. If you get above that you’re given a kickback of some money at the end of the year, which for like I’ve seen it in our own institution surgeons get more back at the end of the year, then I would make all year by much more, you know, because they look the reviews, they give them back but that’s incentivizing people just to Bill and not understand what those costs are or if there’s something that’s equally or more effective, but cheaper.

Geoff Allix  44:55

Yeah, it’s not it’s not incentivizing people to actually make make them well is it?

Richard Burt  44:59

Physicians are not taught to think that way. And I call that financial toxicity. It’s like, if you go to get your car fixed, and the dealer, you know, you just need spark plugs, quick tune up spark plugs, you come back and you got new brakes, you got new hydraulics, you got new tires, the spark plugs here, they were built by some company for Lamborghini in Italy, and they’re $1,000 each, you’re not going to pay for it. You’re saying what is this? You know, I wanted some $25 sparkplug. But medicine doesn’t work that way, and you don’t have a say in it. And doctors aren’t aware of the cost, they have no idea. So what happens is, we are trained to think about the best medical care or, you know, and then secondly, not as well trained, but think about the psychological care of the patient. But medical care and psychological care fail, if financial toxicity is there, and the patients can’t afford it, or the society can’t afford it. Because what happens in a system like England, when they can’t afford something they think it’s too expensive, they won’t approve it. And if it’s, they often look at the upfront expense, not the expense over a long period of time. So, you know, if we are publications, you know, you go phase one, phase two, and phase three, phase three is the randomized, okay, that means it’s great, go forward, for anybody. But there’s never a phase four, where you look at cost effectiveness, what you’re doing against everything else out there. Cost effective means not only the cost, but effectiveness trends and outcome and duration of outcome. So when you look at transplant, it’s a one time thing, and then you don’t need anything for the rest of them. It’s markedly cost effective. But it’s not compared to all these drugs that are the same cost every year over and over and over. But people don’t think that way, because they’re not taught that way. And so if physicians are taught that they need to be a physician, not just medically, but financially for the patients, it would markedly change this out of control acceleration of costs for medical care. By doing that, then you’re allowed to give more medical care to more people. So I call it what we want to achieve is advanced, affordable, accountable, and all inclusive. Those are the four A’s, everybody should think about legislative people when it comes to medical care. But those principles compete against each other. Sometimes, if everything’s all inclusive, everybody gets it, it’s not going to be the most advanced, because you know, it’s too expensive. So by letting physicians have the power to direct the best care, but also, when you’re looking at it, it’s more affordable. You’re putting a checks and balance of cost on the systems and getting it made affordable at the bedside for that patient for that physician, who are the group that really know. So it’s empowering the physicians giving them the ability to understand costs. And then by getting patients the most cost effective therapy, they’ll get more patients coming to them, which will be their reward where they’ll benefit. Unfortunately, our system where there’s whether your employer is a government, or a hospital isn’t structured for that. And that’s why these medical costs are so out of control. And then that’s why they’re limited. So they’re not all inclusive, we want medical care to be all inclusive, everybody should be able to get everything, we want it to be very advanced. Well, that makes it expensive, you know, initial research, and everything is expensive. And that’s got to be offset by something. And then of course, we want it to be affordable. We want it to be accountable. You know, there’s, it’s you have a person not an institution or a system, or government because they’re not accountable. They’re not to a person. So you need a physician that represents you. It’s like if you go to a courtroom, if your lawyer is an employee of the judge, you’re not going to feel very good about him representing you, if your lawyer is an employee of the prosecuting attorney who’s prosecuting you, you’re not going to feel you got good representation. So when a physician is an employee of the government or private hospital or a private company, they have to have loyalties and follow what they’re told by the system which is functioning to feed itself. What you need is a system that’s patient centric, that protects that one patient and a physician can do that if he’s an independent physician, and that’s because medicine is a profession, but healthcare is a business and this business aspect, physicians have not been taught or even think about taking control, but they should, because that will make medicine more affordable and more accountable and with more money available, more all inclusive. And so you can say well, in some government system is more all inclusive than in America, but then I’ve seen time and time again in those government run health care systems where it’s limited.

Geoff Allix  50:05

Coming from the opposite side. So from the NHS system in the UK, that what we get is free at point of views, which is fantastic. So I haven’t, had to have any insurance to have Alemtuzumab, I didn’t pay any money for it. They, you know, the hospital stay was paid for everything. But we have a limited choice, because we only have what’s been signed off by the central board as effective. So things like simple things like medical marijuana, very, very hard to get it in the UK, which I’ve spoke to people in America, they find it extraordinary. They go, well, hang on. But you’ve got MS. Surely you can get Medical Marijuana here? No, you can’t. Because they’ve decided that it’s, you know, it’s not approved. So although if we were in Scotland, it would be, it’s very bizarre that you get these someplace you can, some places you can’t.

Richard Burt  50:59

Yeah, absolutely. So what I hope is that people read this, and people who write legislation read this and understand that, you know, how do you healthcare so complex and so large? How do you make constructive change, because there’s repercussions that are unwanted, whenever you tweak on one string, they’re all interconnected. But you know, again, it’s the four As advanced, accountable, affordable, all inclusive. But those are competing demands. And the way you do that is you put checks and balances, where they can check and balance each other. One big way to do that that has never been done is demand that these publications have a final phase four with cost effective analysis. And then the physicians understand the cost of what they’re making a patient or insurance or society pay, and figure and the effectiveness of it for that cost. So that, for instance, just quality of life, all these DMTs have never been shown to improve quality of life. Transplant does now some of the newer ones, they have a numerical improvement of quality of life by one or two points. So they say that’s permanent. But that’s meaningless, because to an individual patient improvement of quality of life and the SF 36 must be a minimum of five points for them to feel it. So it’s typical improvement, but clinically meaningless improvement. Whereas in transplant, it’s 15 to 25 points. So it’s a very clinically meaningful improvement. Obviously, if you neurologic get better, you get off drugs and all their expense, cost and time and side effects, of course, quality of improves. So you need that fine on everything quality of life and cost effectiveness. And then in physicians who are not happy, handicapped by being employees that have to function to feed that system above, because they’re the money revenue generators for the system above. But who can then function to represent their patient. And in the UK, okay, there, the money revenue is coming from the public health system, but they’re being controlled by that public health system, and administrators who are totally distant from a lumbering bureaucracy that doesn’t know and is not involved in can’t change on a dime for the patient sitting in front of them. But if they know and they can, the if the physicians are independent professionals, medicine is a profession, if they’re independent, then they could direct to make sure, you know, it’s it’s the most cost effective therapy. And that’s what’s been missing in medicine. So, you know, I accomplished this, and patients would say, who’ve done this, I don’t understand why aren’t institutions people screaming off rooftops that people get this? It’s because of the way the system’s gotten structured, and one of them is financial toxicity. And so, you know, by making these subtle changes, that things like this would come to patients sooner, and they’d be offered a lot faster.

Geoff Allix  53:50

So to wrap up, this has been quite a long episode now. Firstly, I think everyone would agree there definitely could be improvements into the in the way that healthcare structured, regardless of whether that’s in a system, like the US, a system like the UK, or the many systems in between the two. And I think I absolutely agree with what you’re saying. It’s, yeah, critical, and who knows, there could be changes. I mean, it has been Michelle Obama’s mother, I believe, had MS. Mitt Romney’s wife, I think has MS too. You know, maybe there’s some politicians might get more involved if it’s, it’s closer to home. But and the other thing I would say actually, the other big thing, obviously, we’ve covered is HSCT. So I’d absolutely encourage people to have a look in the show notes. We’ve got links to your book. You know layman’s because I think a lot of it is technical of what I mean I searched on the internet, but a lot of it is is difficult to understand from someone who’s not got a specialist background. But yeah, a layman’s guide that would be absolutely beneficial. So yeah, have a look for that. And but I want to wants to finish up. You mentioned the Dalai Lama. Because the Dalai Lama  did the intro to your book everyday miracles. And the Dalai Lama very much promotes mindfulness meditation. And this is one of the programs of the Overcoming MS approach. So using stress relief techniques like mindfulness meditation, do you see that there’s an intersection between that mindful aspect and medicine.

Richard Burt  55:36

So this book is about transplant and patients going through it and their diseases. It’s not about meditation, per se, or mindful meditation. It’s just not about that. You know, I was very blessed that the Dalai Lama wrote the foreword, I am not in any way qualified to speak for him. You know, he was just a blessing given to me.

Geoff Allix  56:00

So how did how did that come about though?

Richard Burt  56:03

As I said, I’m not qualified to speak for him, it was just a blessing. But finally, you know, I’m working in IPS in animal models, we’ve developed real neuro regenerative potential. And we want to, we’re working to try to get that we have seven patents on our IPS work. We started a little biotech company, and I’ve been trying to get those to the patient’s bedside it be simple. It’s not for stopping an immune attack, like HSCT does. It’s for these late neuro regenerative or just neuro degenerative processes, and as well as actually repairing any organ or age system. That’s we’re working on, and it’s simple, it’s just injection of the cells. But there’s, there’s a whole different set of hurdles that we have to get through. And we’re working to get there.

Geoff Allix  56:55

And that could be for something with progressive for people, with progressive MS as well?

Richard Burt  57:00

Absolutely. And that maybe someday will be addition to of this book. If I live long enough, and it’s a whole different set of hurdles. It keeps you young. But again, you know, these if these things were easy, everybody would do it. So it’s a lot of things we’ve got to accomplish, but we’re working on it. And when we want to go to clinical trials, it’s now getting over there, those hurdles to get there.

Geoff Allix  57:27

With that, thank you very much for joining us Professor Richard Burt.

Richard Burt  57:30

Thank you so much.

Overcoming MS  57:35

Thank you for listening to this episode of Living Well with MS. Please check out this episode’s show notes at overcomingms.org/podcast you’ll find useful links and bonus information there. Have questions or ideas to share? Email us at [email protected] or you can reach out to Geoff on Twitter @GeoffAllix. We’d love to hear from you. Thanks again for tuning in and see you next time for tips on living a full and happy life with MS. Living Well with MS podcast is for private non commercial use and exists to educate and inspire our community of listeners. We do not offer medical advice for medical advice please contact your doctor or other licensed health care professional