Continue Learning With Dr. Burt and Be Inspired to Question Dogmas (Ep. 97)

Zen Jen: Good morning, Dr. Burt. It’s so great to connect with you again.

Dr. Richard Burt: Good morning.

Zen Jen: How are you doing?

Dr. Richard Burt: I’m doing good. Thank you.

Zen Jen: So last we spoke, I wanted to squeeze in some questions and I appreciate how much you’ve shared already about the book, and your intentions. And, some part of the book that I know so many people have questions about, or at least those who are desperate to get to HSCT, might be curious to know more about why you’re saying HSCT is not as effective for primary progressive MS or even non-active secondary progressive MS.

Dr. Richard Burt: Well, that’s because HSCT, despite its name, hematopoietic stem cell, that is stem cell transplant. It is not a tissue neuro regenerative therapy.

Zen Jen: Mm-hmm.

Dr. Richard Burt: It is an immune [00:01:00] reset therapy. So, once MS transitions from an immune mediated inflammatory disease into a neurodegenerative disorder, which is what non-active secondary progressive MS is, uh, this therapy is too late to help it.

Now, primary progressive MS, I think upfront is a different disease than relapsing-remitting MS. Obviously, it s clinical course is different, but uh, it just happens to be called the same thing. Multiple sclerosis. I think primary progressive MS is really a predominantly neurodegenerative disease from onset, whereas relapsing-remitting MS, it’s not. It’s a immune-mediated inflammatory disorder that results, as time goes on with accumulation of, of plaques and demyelination in a neurodegenerative [00:02:00] disease. And the reason it results in that is that the neurons are incredibly specialized cells and some of them will have a, an axon or a body that goes from the cell nucleus in the brain all the way down to the lumbar sacral region in the spinal cord.

And when you think a very, very small microscopic cell can do that, that’s an astronomical distance that it travels. And in return for its very specialized functions, uh, that give us cognition and, uh, you know, control of motor function and a lot of other functions in our body, it needs, it sacrifices certain other attributes that cells have, and it needs the support and nourishment of other cells, including uh, oligodendrocytes that form the myelin around these axons. And so, uh, once those are damaged, you can start setting your neurons up if they’re [00:03:00] damaged significantly enough for an accelerated, uh, neurodegenerative process.

And so, you know, that’s where you end up with late non-active secondary progressive MS. But my concern is that, uh, primary progressive from onset is a different disease. That it’s, uh, predominantly neurodegenerative and an immune-based therapy, which is really what HSCT is, that is resetting your immune system back towards tolerance to, uh, to myelin epitopes, would no longer be effective.

And so why put a person through the risk? Of this treatment, if, if it’s not gonna help ’em. You know, if there was absolutely zero risk or inconvenience from this therapy, you know, that you could maybe argue differently until you’ve collected enough data to publish and confirm it’s, whether it has any effectiveness or none at all.

Zen Jen: sure.

Dr. Richard Burt: In primary progressive MS, but it, it, this there carries a low but real risk of [00:04:00] mortality with, uh, HSCT. Depending on the regimen you use, it’s higher with myeloblative toxicity, mortality, but even with non myeloblative, you can never make that risk zero. And so that’s why, you know all ,what all medications, all treatments, all surgeries have early and late complications. Um, you know, so you, you always have to weigh risk benefit and, um, you, you know, I personally would be uncomfortable with that risk when I strongly believe there’d be no benefit. And I think the converse could be said that, you know, it could be easy to argue that people that do that are either being kind of naive, or that there then would be taking advantage of patients for their money without being able to help ’em. So I think pretty much anybody that has experience doing H SCT for uh, MS will not do primary progressive or late secondary progressive [00:05:00] MS. In the early days we did before people figured that out. So, um, you know, I, I figured that out very early.

My very first paper of 10 patients, I put in the title “failure” for late secondary progressive MS ’cause I wanted people to understand that. And in the early days, you know, you had to start there. Uh, you know, we were, I had animal data that it worked in relapsing-remitting, EAE an animal model for ms, but not in chronic EAE, which is like, secondary progressive MS, but nevertheless, ’cause nobody had ever done this in terms of risk benefit,

Zen Jen: Mmm.

Dr. Richard Burt: You know, we were restricted to starting the secondary progressive and that really followed the animal model. You know, it just doesn’t benefit those patients. Um, I mean, you know, there’s a subset if their EDSS is less than six that didn’t show further progression, of the EDSS over several years, and you could argue maybe it stabilized them, but I, um, that would require a gigantic study. And, uh,

Zen Jen: absolutely

Dr. Richard Burt: it just didn’t interest me. And, and [00:06:00] those over six, many of them continued to progress after the procedure. So it’s, you know, MS, even relapsing-remitting, I think, is a little heterogeneous. Obviously, it’s clinically heterogeneous. Some people have very explosive disease, others very mild, uh, you know, where they have very few attacks during their life.

Uh, some, you know, have multiple lesions on MRI despite limited disability. Of course, that depends where the lesions are, but you can be surprised by that. Others have not so many lesions and a lot of disabilities. So, even relapsing- remitting, is a spectrum of, uh, or variations, at least, uh, in its clinical presentation.

Whether they’re variations in the underlying pathophysiology isn’t clear, but there, I think as time goes on and more research has done, these will eventually be better clarified. For instance, it used to be considered that neuromyelitis optica also called Devic’s was just a type of MS [00:07:00] and it does cause demyelination.

And when it first starts, it’s predominantly in the spinal cord and in the optic nerves, uh, with sparing of the brain, which makes it a little bit unusual for, uh, MS. Although MS involves the optic nerves and the spinal cord, but the lesions in neuromyelitis optica tended to be confluent over at least three vertebra.

That is, they follow the length of the spinal cord for at least three vertebra, whereas MS tends to, when it has a lesion confined to the length of one vertebra, if it becomes confluent, it can look like it’s three vertebra. But you know, the initial attacks are just the length of one vertebra. And, uh, neuromyelitis optica initially didn’t show lesions in the brain, but as time goes on, you often do get lesions in the brain. Um, and so it used to just be considered a type of MS that would present more with, uh, spinal lesions and optic neuritis. In fact, the way it was first described was about, I think it was 1894 French physician, Devic, for which it got the name.

[00:08:00] Eugene Devic was his name. Neuromyelitis optica had a patient come to him with first attack and uh, within a month had died. And an autopsy showed extensive involvement of the spinal cord and, and optic nerves. But the brain was normal. And so, you know, he wrote it up as neuromyelitis optica, uh, and um, you know, his name Devic got associated with that.

And then for a hundred years people argued that it is just a type of MS and was considered MS. But over time that’s been teased out because an antibody to astrocytes, not to to oligodendrocytes, not to neurons, but to astrocytes, uh, was found to cause the disease. And that’s an antibody to Aquaporin-4, uh, whereas you don’t see those in MS at all.

So, it’s a, it’s a much rarer disease than MS. MS is about one in a thousand, uh, in people of [00:09:00] European heritage, but MS is relatively common in, in the Middle East too I’ve, I’ve learned, uh, but the, uh, neuromyelitis optics is about one in a hundred thousand. So it’s, it’s, it’s less common, but, uh, and it does respond to transplant, but we have to use a different regimen than we use for MS.

So, you know, going back to your question, I think that primary progressive is a different, uh, disease than ms. It just happens to be called primary progressive MS. Uh, and so that’s, and I don’t think a stem, a immune-based or immune regenerative therapy would be beneficial. If someone ever proved me wrong, that would be great,

Zen Jen: Right.

Dr. Richard Burt: but, but I don’t think that would be the case, and I don’t want to put patients through the risk of this therapy if I can’t help them.

Zen Jen: Sure. No, and I so appreciate you taking the chance on me as I transitioned to secondary progressive [00:10:00] between my first evaluation and insurance approved me and then changed their mind. And so then six months later I thought, well, let’s go again for an evaluation to just help make the proof that I’m getting worse and I need this as a medical necessity, right? That it’s, I need this more than ever. And sure enough, six months later, I did not have active lesions and we were, you were afraid that I was transitioning to secondary progressive and that within a year, this may not help me and I’m just beyond grateful that you took the chance that it would help, because I believe that it has.

Dr. Richard Burt: Well, yes, I think we can still help people with active secondary progressive, that has new lesions or an active enhancing lesion within the last year. But obviously once you get to non-active, secondary progressive illness, then I, I don’t, I wouldn’t offer the therapy. Ideally, of course, you want to get people before they get there.

Zen Jen: Yes.

Dr. Richard Burt: Uh, obviously we have to fight with the insurance companies to get this to happen. And in your case, there was that long delay bef, you know, to, [00:11:00] work that process through. Uh, and I’ll leave that up to you if you want to tell your readers, but, um, you know, it’s, um, one of those things you have to do that’s different than what most doctors do. So when we, you know, most doctors don’t write and submit, and take the time

Zen Jen: no,

Dr. Richard Burt: for, for their submitting to insurance companies, and then going through all the appeal processes. And it’s quite a bit of time and effort for which there’s never any reimbursement, but you do it because you want to try to get the best therapy for your patients and, you know, it can, uh, be a time consuming, uh, process, uh, almost at times like writing a grant. And that,

Zen Jen: indeed,

Dr. Richard Burt: you know, the result is, uh, whether the, you know, the funding shows up, is never in your hands, but it’s the process we have. And so, you know, we work with it to try to get the best we can for the patient.

Zen Jen: And so, going back to what you just [00:12:00] mentioned about the antibodies related to NMO, neuromyelitis optica. I’m just beyond impressed, continually impressed, with how much you know as an immunologist by training about these neurological conditions, and I’m grateful for your dedication to that research. So, if we think about the latest research out of Harvard, that Epstein Barr virus can cause, or trigger the body to develop multiple sclerosis, what do we know now, about Epstein Barr, as it relates to the antibodies. You mentioned this briefly in your book, right, that some of the more harsh regimens or myeloblative regimens can trigger that Epstein Barr virus antibody reactivation, and I know that that was the case for the first patient treated on the Beat-MS trial at Cleveland Clinic. That there were a few weeks there, that the fever was super high and the antibody levels were 500 times what they should have been. [00:13:00] Maybe talk a little bit about those risks with myeloablative and why reactivation of Epstein Barr can be such a challenge.

Dr. Richard Burt: Well, you know, there’ve, there have been intermittent reports through the decades of different viruses, uh, being triggers for MS and they kind of, um, have their period of interest, then it kind of falls off, uh, and then recurs later with a different virus or, uh, re-interest in a particular virus. They’re, they’re often herpes related viruses, and Epstein Barr, who is within the herpes family, but other, there’s also been this concern with other herpes viruses. Um, and that’s not been my, you know, there’s no definitive answer to the involvement of virus in, in MS and that’s been not been my particular area of research.

I did do research an animal model of Theiler’s Murine Encephalomyelitis virus, which causes a disease that mimics MS. It actually mimics primary progressive MS, not [00:14:00] relapsing-remitting in an animal model. And, uh, um, you know, that attacking the virus in the central nervous system and the inflammation of the response to that attack causes a presentation of some myelin proteins to the immune system in an inflammatory state, and so that can activate, that can remove tolerance and activate the immune system against myelin proteins. And that, once activated against one myelin protein and the attack starts on that protein, it can spread to other myelin proteins, and that’s called epitope spreading. So, yeah, viruses have a potential kind of a, a bystander potential by activating the immune system to, if there’s damage to other tissue within the area, to activate the immune system to, to self peptides. Uh, it’s one of the things like when we would cause MS in animal models, you know, [00:15:00] we could use a virus -TMEV -that would cause a disease, looks like primary progressive MS, or we could, uh, use just myelin peptides by themselves. But if you inject those peptides, absolutely nothing happens. If you inject them with an adjuvant, that is something that stimulates the immune system, you could trigger the immune system to cross over and attack myelin and start a disease called EAE that mimics MS and that adjuvant that you use could be complete Freund’s adjuvant, which is, you know, kind of dead mycobacterium.

Or it could be , any of the normal vaccines that people are giving, measles, mumps, rubella, tetanus, they would all activate the immune system and could lead, if there’s, uh, myelin peptides, co-injected with it, then to the development of MS. So, it doesn’t surprise me at all that viruses could play a role, but the definitive role of a given [00:16:00] virus for MS, I don’t think has been absolutely clarified.

Coxsackie for, uh, type one diabetes is probably a better example and that one’s more closely, um, associated with onset of Type I diabetes in, in children. So, you know, it’s kind of understanding how the immune system responds to self peptides. And, it used to be in the old days, thought that during development of your immune cells from the hematopoietic stem cell would have to start differentiating towards different immune cells.

But saying the development of T cells, the way it makes a T-cell receptor, is it, randomly rearranges these different genes and comes up, it can develop millions and millions of different receptors on the T-cell. The problem is that random rearrangement in the development of the T-cell will develop receptors that recognize self epitopes or self tissue [00:17:00] or self antigen, and it used to be thought in the development of the T cell receptor, if it bound self, it would die. So these self reactive T-cells don’t get in the periphery. That’s only partially true. It’s then subsequently realized that it has to bind self to get into the periphery, but it has to bind self in a weak to moderate manner. If it binds it more intensely, it still survives, but becomes a T- regulatory cell to down-regulate immune response.

If it binds it super strong, it dies and may, right, probably good that it does, so it isn’t too auto-reactive, but your T-cells are all potentially auto-reactive, but they’re allergic to self. But that means they have the potential, given the right co-stimulatory signals and the right inflammatory environment to cross react if the epitope is there to self.

In fact, that’s really the reverse of that, is how transplant works. If you knock down your immune cells, get rid of [00:18:00] enough of the self reactive ones and stop the inflammatory process, the regeneration of your immune cells will default towards tolerance, uh, with uh, T- regulatory cells that help maintain that tolerance.

And, uh, I’m sure with time, that will be elucidated even further. You know how that mechanism actually works, but that’s really, how this works. It’s kind of the reverse of immunization. It’s just quieting down your immune system, getting rid of a significant number of auto-reactive cells and allowing the regeneration of cells that have the potential to react to self, but do so in a non-inflammatory environment.

And that resets tolerance, uh, including the development of the T-reg cells that have a higher avidity for self epitopes, but, but help maintain tolerance. And I think one of the advances further in, than transplant for autoimmune diseases would be [00:19:00] to see if there’s something you can do to the, uh, regenerating immune system to help push the production of more T-reg cells, or that is more, uh, uh, cells that help maintain remission, uh, and help shut down any potentially activated, uh, cell once it becomes activated towards self.

But, um, that’s kind of a theoretical future. There are people that work on T-reg cells for that reason. And I mentioned that in my academic textbook, uh, which came out in November, 2021. We have a really great chapter on T-reg cells by a professor in London, uh, and their potential role, you know, uh, so, and there are limitations currently, there’s still a lot to be learned. Um, so, um, going back to your question, though, the intensity of the regimen does determine reactivation and risks of viruses subsequently, uh, [00:20:00] and, you know, Epstein Barr virus has never really been a concern for us when using a non-myeloablative regimen. But you can use non-myeloablative regimens that are just as intense or even more intense on removing your immune system than a myeloblative one.

And actually there are people who use a non-myeloablative regimen of Cytoxin, ATG, but they increase the dose of ATG to around 7.5 milligrams per kilogram. And once you call above 6.5 milligrams per kilogram with ATG, you start running into the risk of reactivation and disease associated with Epstein Barr virus that you don’t see when you keep the dose around, you know, you cap the dose at six.

Um, it’s… the other thing they do is CD 34 select, which you know, is purifying the graft and may also contribute a little bit to that. But those are the two reasons why, you know, when you, you have, when you look at the treatment for MS, there are all these different drugs, disease [00:21:00] modifying therapies, and people know natalizumab is different than Lemtrada that’s different than Copaxone in terms of efficacy and toxicity. For, for instance, natalizumab, uh, is the biggest risk for the virus, progressive multifocal leuko that causes progressive multifocal leukoencephalopathy. That is the JC virus. Other drugs have a very low risk that it has been rarely associated with Ocrevus or Gilenya, but it’s very rare developing that disease.

Unlike Natalizumab, uh, it’s really unheard of when you use Copaxone or Interferon. So, it’s the same with conditioning regimens, and unfortunately when people think of transplant, they think of just this monolithic block called transplant. But no, it depends entirely on your conditioning regimen. And the first way you can break that conditioning regimen down is whether it’s myeloblative or non-myeloablative.

But then even within that subset, there’s different levels of risk and risk of viral reactivation. And certainly when you use a very intense regimen or even a [00:22:00] non-myeloablative with ATG dose over 6.5, you uh, run the risk of, uh, of reactivating Epstein Barr virus and having uh, complications associated with that, including, um, uh, PTLD post-transplant, lymphoproliferative disorder.

So, um, yeah, the, regimens can absolutely be associated with different risks of toxicity and, uh, virus related infections.

Zen Jen: thank you

Dr. Richard Burt: and, it’s one of the reasons I’ve always argued for the safer non-myeloablative. But within the non-myeloablative, I’ve argued to the community to cut that ATG dose back to less than 6.5 and that CD 34 selection is not necessary.

And I think that message finally starting to resonate with those who have used the higher Cytoxin ATG regimen. And they are, I think, in the process of, uh, reducing that. [00:23:00]

Zen Jen: Wonderful. So do you think that virus might be a factor in triggering relapses for people who have been through HSCT?

Yeah, I don’t have an answer to that and I haven’t personally seen that in patients. Uh, fortunately the majority don’t relapse. But in those that have relapsed, I haven’t noticed an antecedent viral infection as the precipitating cause.

Zen Jen: Well, that’s good to know. I’m just always curious. I think a lot of people are curious how that relapse might occur and understanding might help resolve some of the anxiety around even at five years post-transplant. I still, if I get sick, right, I’m thinking, oh my gosh. Is my MS coming back? Have I relapsed?

Dr. Richard Burt: Well, it is clear when you have an infection that you can get a pseudo-flare, a recurrence of the symptoms, but it’s not associated with recurrence of MS. And as the infection goes away, the pseudo-flare [00:24:00] resolves. There’s no new lesions or activity on MRI and you continue to do well.

But you know, once the central nervous system has been damaged, it’s more prone to re-manifesting those symptoms when you’re under stress, whether, especially with an infection, but also even, you know, intense uh, stress from employment or marital stress or whatever, inner-relationship stress. Uh, and that’s, that happens with other types of damage to the central nervous system. Even if you talk to patients who’ve had, uh, slipped disc with pressure on, uh, the nerves coming off the spinal cord and then finally go to surgery and they get relief, you know, it’s not unusual with stressful situations for that back pain to act back up just like a slipped disc. And you know, they have to go to bedrest and stuff and when the stressful situation resolves, uh, they go back to where they were, uh, you know, before without that type of, uh, [00:25:00] radicular pain from a, from the prior herniated disc. So, the central nervous system, once damaged, no matter where it is, can, is, is prone to, under, uh, different types of stress or infections to re-manifest those similar symptoms that do resolve once the, the uh, stressor or infection resolves.

Zen Jen: Thank you for clarifying. I hope that brings some peace of mind to our listeners and, so, many of the people I interview, I like to ask a question. About a superpower that they’ve gained through their experience with HSCT. So, some people point to increased patience or resilience, tenacity, increased sense of empathy.

All of those things seem to already be part of who you are, but I would love to ask you, if there’s a superpower you’ve gained in your experience with [00:26:00] HSCT.

Dr. Richard Burt: (laughing)That’s great. I wish that was true. If it was true, many more doctors would be doing this. It’s more like hitting the UFC ring and getting pounded on uh, despite doing a lot of good and, and, uh, you know, it takes a lot of perseverance and, and, uh,

Zen Jen: yeah, it does,

Dr. Richard Burt: you know, you do get fatigued from, uh, working that hard and dealing with, uh, all the uh, misinformation that occurs out there. What I have learned is that, you know, I mean, I’m obviously a professor and I love learning and uh, teaching, but, um, and information is valuable, but limited information is very dangerous. Uh, ‘cause people take that and they twist it in ways and it really is unfortunate.

And so you get limited information‘cause you are not doing the work yourself. That’s where you get the most information. By designing the protocol, studying the disease, and doing the treatment and sitting at the bedside 24/7. [00:27:00] Then you live it, then you know, and when you do that, and then you see how other people, you know, no matter who they are, including doctors, get up and talk about it, who don’t actually live it or don’t even necessarily do it, you’re like, whoa, you know, no wonder things are so confused out there.

Uh, so, you know, part of the process is trying to educate people about how this works and the risk benefits and, and so forth. But, um, um, there is developed just tremendous misinformation out there that’s kind of destructive. You know, ’cause people often, the first thing they hear, they tend to latch to it and stay to it is hard to, it’s kind of that first effect and it’s hard to get people to open their minds to rethink it.

So, um, it’s maybe one of the things that have hindered the development in this field. People are taught in a particular way, and so, you know, once they hear the word HSCT, they, [00:28:00] they don’t really understand what it’s about, but yet they’ll convey a lot of information and they’ll have different degrees behind their names to do that, which would imply they’re an expert.

But no, they’re not. They actually didn’t develop it. They don’t sit at the bedside. They’re not taking care of those patients and they’re in, and they can then, unintentionally, uh, cause the distribution of a lot of misinformation. And so, you know, you get tired of that, you get exhausted seeing that over and over.

Uh, and in fact, I’ve kind of decided, you know, after all my publications, and my major medical textbook last year, and this lay book, you know, if this doesn’t help change things in this country to make it more accessible for patients. Then, uh, then I’ve probably done all I can do.

Zen Jen: Mm-hmm.

Dr. Richard Burt: you know, the, the system is kind of this gigantic bureaucratic structure that marches forward on its own and the patient’s [00:29:00] gotten lost in that structure. Uh, you know, the system is developed for the patient, but it’s not patient-centric anymore. And what you need are physicians that are patient-centric and that patient is first. And I bring that out in the last chapter, uh, especially in the last chapter where I talk about, uh, financial toxicity.

So, you know, hopefully this will, but that’s gonna require some subtle changes in the medical system itself, which is kind of beyond my authority to do. It’s more of a societal thing and legislative thing. And so in a kind of a redirection of, uh, how doctors are trained and think, uh, because it is, patients would say to me, why don’t people stand on rooftops screaming about this?

And, uh, you know, I didn’t really have a good answer for that. I, kind of didn’t understand that myself and from being in the, in the ring all this time and, you know, you kind of get tired of knowing what you’re doing [00:30:00] is the right thing, but getting beat on. So, um, it, it is actually surprising to see these kind of responses in this disease and yet a failure of the community, including the academic community, to embrace it.

Uh, so, you know, I bring out in the last part of the book, the last chapter, what, you know, Why I Can’t Get HSCT, and uh, it’s not critical of any one person. I don’t believe in any way that any one person or entity is intentionally trying to harm a patient. I think it’s quite the opposite. I just think it’s limited information and set ways of thinking.

And then as the, the way the structure feeds on itself our medical healthcare system and it, you know, needs to be reemphasized and tweaked to make it patient-centric, uh, instead of just expanding itself. Uh, so hopefully, you know, there’s several levels to this book, Everyday Miracles, and I, I hope you know, that [00:31:00] people understand those different levels.

One of the levels is just understanding these diseases, which, another level is the patients and their tremendous courage, and fortitude in human spirit to persist and survive. Uh, and to try to find a way when you’re being told it’s a chronic disease and you know, basically you’re stuck with it.

And so, there’s another level, and that is the inherent problems that have occurred within our medical system that need to be tweaked to make our medical system advanced, accountable, affordable, and all-inclusive. And you know, medicine is a profession, but healthcare’s a business and that’s where conflicts can arise.

And you really do need an independent physician who’s not an employee of a hospital or an institution, to represent you through that healthcare business. Not just in terms of medical, which they currently do, but in terms of financial. And uh, um, you know, that is [00:32:00] not being done. Doctors have absolutely no clue about charges to patients. Uh, and, um, at the end of the year, they’re given a bonus if they exceed their expected billing. And if they don’t, you know, they get penalized by, you know, uh, various psychological pressures or taboos or, you know, kind of almost like putting a scarlet letter around their neck and, uh, then less, you know, revenue for the next year.

And, you know, that shouldn’t be. It should be focusing on doing the best for your patient. And if, uh, you know, you’re not concerned about the financial health of your patient. If there’s financial insecurity, whether it’s for the patient or the society, the medical and psychological health of your patient will also suffer.

So, you know, obviously if you take a chronic disease, it’s being treated with these extremely expensive drugs. And I point out the cost of the drugs when they’re first approved by the FDA and their current cost in 2020. And its astronomical shift going from the original [00:33:00] copaxone, interferons that are about nine to twelve thousand a year to, you know, a hundred thousand dollars a year.

That’s matching the development of the new drugs. They’re all running kind of the same price. So, a transplant using the regimen I do, non-myeloablative, would be paid off after one year and then you’re free the drugs and it’s done something the drugs haven’t done. It’s reversed neurologic disability by one to two points and uh, it’s improved quality of life and the majority, 75% have remained free of recurrence of MS. Uh, not just relapses, but progression. So you know that, you would think would be welcomed in the community.

Zen Jen: Mm-hmm.

Dr. Richard Burt: But it’s, it kind of hasn’t been, and it’s kind of been a, a fight to get the community to understand that. And that includes some patient support groups the, traditional ones that, uh, have been lag, you know, very far behind in recognizing or supporting this. And again, I think it’s because, they’ve moved away from being patient-centric,

Zen Jen: [00:34:00] mm-hmm

Dr. Richard Burt: And, uh, large structures do that, yet the development of those structures was originally to help the patient in front of [th]em. And often the larger the structure, the more money involved, the more uh, they become self invested in continuing their cycle and that, the patient kind of gets lost.

So you need a physician that’s patient centric and they can’t be if they’re an employee of a hospital or whatever, ‘cause they have their own different structure and interests to allow those gears to expand. And they, they live off the revenue brought in by that patient care. So, you need a doctor that can fight that without risk of losing their or suffering some disadvantage for standing up for the patient.

And, um, uh, you know, it’s kind of like if you’re, need a lawyer, but the lawyer works for the judge, or works for the district attorney that’s prosecuting you. You’re not gonna get the best lawyer ’cause he’s compromised. And it’s the [00:35:00] same this way. You need to, to have doctors that are not employed by hospitals or large organizations whose primary focus is you, because they have the knowledge, but they’re, they’re totally excluded from understanding charges and billing. And part of that requires then, that uh, medical journals, you know, they normally will publish phase one, phase two, phase three, phase three being a randomized trial, but they don’t publish cost effectiveness. There’s never a phase four. What’s the cost effectiveness of this?

That is the cost for this and the benefits versus other types of therapies. So people don’t know. They’re unaware. And I bring it out in Neuromyelitis Optica. I bring it out in, uh, in uh, MS as well in those chapters. But for example, neuromyelitis optica in 2019, the first drug was FDA approved for neuromyelitis optica.

It’s Eculizumab, it costs three quarter of a million dollars a year and you have to stay on it forever ’cause it doesn’t get rid of the, or effect in any way, the antibody that causes the disease, the Aquaporin-4 antibody, [00:36:00] what it does is block activation of complement by that antibody, it’s the compliment that destroys the cells and causes the attacks, but you can still get attacks. They’re just less frequent.

Uh, but you kind of just stay on it forever. Whereas the transplant I showed, although it was a small number of patients, you know, phase kind of one study, we did show that the majority, 80% became negative for the antibody. And if they became negative for the antibody, they hadn’t relapsed over five years and the patients I reported in Neuromyelitis Optica were beyond 10 years without a relapse or any treatment. So if you, the transplant, the regimens have to be specific for each disease. The regimen for neuromyelitis optica is different for MS, it’s a little more expensive, 125,000, but you know, you could do five transplant in one year for the cost of one year of neuromyelitis optica, but nobody’s aware of it.

Zen Jen: Mm-hmm.

Dr. Richard Burt: And it’s really been you, whether it’s the insurance company or the government paying for it, it’s still the society as a whole and it’s not sustainable, and I call [00:37:00] that financial toxicity. And it’s not unique to neurology. I’ve seen it repeatedly throughout all fields of medicine. And it’s because doctors have absolutely no training in cost effectiveness or the cost for their patients.

And especially when they’re employees, they don’t even know what those books show. Uh, they’re just pushed to, to increase RVUs, which is revenue built. So, you know, which is functioning to support the system over the patient. And that’s why I try to bring out, we need to become more patient-centric. And that’s where medicine really started.

But that’s gonna require some societal changes in the structure of medicine that go beyond me. And so those, there’s several levels to this book that I wrote and you, you know, may have to read it a few times to pick up on those different levels, but of course one of the obvious ones is here’s patients that are just continuing to get worse on these drugs. A system that is fought against them independently on their own, they came for transplant and they’ve gotten so [00:38:00] much better, doing well, uh, without any drugs, for now very long periods of time and some of the patients I just randomly contacted 20, 15, 10 years out, still in remission doing well.

So again, there’s no definition of cures for these diseases ’cause nobody’s ever had the luxury to define that.

But, uh, um, it does change the natural history of the disease, and if there is a definition of cure, perhaps the best would be in those few for which we have antibodies such as NMO. Uh, in transplant it’s the only thing that’s ever shown a disappearance of those antibodies, uh, as a caveat, you also have to check for the ability of those antibodies to kill cells uh, that is actively a compliment, but you know, that gets into detail it’s not necessary here.

Actually in MS if there is a pseudo, uh, a, diagnostic marker for disease, and I’m not sure it is, I’m not sure at all that it is, but you could maybe make an argument that it’s the oligoclonal blands and the CSF fluid and, um, the people in [00:39:00] Sweden who were part of my mistrial actually did add a little extension to it where they.

Would do follow up lumbar punctures to look at those oligoclonal bands. And they found that by about eight years after transplant, you know, the patients go into remission, stay in remission, but they still have those oligoclonal bands. And then about eight years after transplant, they totally disappear.

Zen Jen: Wow.

Dr. Richard Burt: So you know, there can be a delay for them, to go away, but they went away. So, you know, they did publish that, but it’s kind of, you know, a lot of people don’t recognize or know that, in fact, I didn’t even put it in my lay book because then it, it would talk about, I would require to talk a little more about the basic immunology of things, which, uh, you know, I, I didn’t want to go into, I wanted this to be a book that’s uh, understood by the lay public.

Zen Jen: Sure.

Dr. Richard Burt: And that they would enjoy reading more of a kind of humanities type of book. And in fact, I enjoyed writing it that way. It took me back to my college days because I’ve been so tied up having to write [00:40:00] in a medical [form]

Zen Jen: medical publications.

Dr. Richard Burt: Yeah, right. Which it’s important to write ’em that way, but you know, they’re loaded with statistical analysis, and they can put you to sleep if you’re not really into understanding and, and doing that. So, um, you know, I wanted to get this out to the lay public and, and write it from, you know, patient’s perspective as well as how this field was developed by me. Um, and, uh, you know, which is another level to this book.

So, hopefully the key is that people read this, I think it will have an impact, but people need to read it. You know, unfortunately, I don’t have the name of a famous, uh, movie star or politician, which people would then want to read, but, you know, they don’t have the knowledge or expertise to, to develop something like this or to do it.

But, you know, all I can do is get the information out there and then let the cards fall the way they will. But, the purpose of this lay book is to empower the [00:41:00] patient and their family and their loved ones. Um, you know, and then they can go to their neurologist, say, see, read this. A neurologist [could] say, oh, well this is science fiction.

But then they can hand them my medical textbook that came out a year ago, or, or my website that I set up. So this information is disseminated to patients, uh, astemcelljourney.com so patients can, can have access to that as well as, as physicians, you know, because it’s almost ludicrous that you can have a, a therapy like this that can have such tremendous benefit. And yet it is so hard to even be made aware of it or to access it.

Zen Jen: It is ludicrous, indeed.

Dr. Richard Burt: Some people have just said awful things about this that are completely wrong and, um, you know, you, you just have to kind of wonder. You know, I think whether there’s other agendas that they have or just, uh, limited information. [00:42:00] And so that’s, that’s the goal here is to, you know, think that people’s intentions are generally good, but the information’s limited. And that’s, you know, one of the reasons I wanted to get this lay book out, as well as the medical textbook. And hopefully those will do more than all the medical publications and clinical trials have done because, you know, they, they don’t seem to have changed the field as, as they should have, or made this more accessible to patients. Then after a while, after decades, I, I get tired of being in the UFC ring.

Zen Jen: Yeah.

Dr. Richard Burt: So it’s not, it’s not a superpower, it’s an exhaustion. I wish it was a superpower.

Zen Jen: Oh, I heard so many superpowers embedded in your response, right? So, I mean, just your vast knowledge in general is a superpower. Being patient-centric and really caring about that improvement in quality of life. To have that as a focus is clearly unique in the field of [00:43:00] medicine, which is unfortunate, and ludicrous. Um, facilitating clarity through education, I mean, you’ve been devoted to that it seems your whole life, if not career.

But I think when you identified the patients evidencing fortitude in human spirit, I’d say, if I could declare you having a superpower, that would be it, I think, although you see it in your patients, I see it in you and

Dr. Richard Burt: well, thank you very much.

Zen Jen: I’m beyond grateful for that. I just truly, am so grateful for you and, and your dedication to this research and to your patients and being at our bedsides because I, I know that that’s true. And if anyone were to ever doubt that, I just can’t imagine, uh, why? I vividly remember even a conversation that we had on a Sunday morning, where you walked in and I was working on a laptop and you said, oh, are you scrolling Facebook? And I said, [00:44:00] no, no. I’m working on a grant application. And so we bonded over the grant process, but you shared a story of growing up in Montana where my sister lives, and so I’m just, I’m ever grateful for our connection, and I hope more people can enjoy a sense of that connection. Just in reading your book, because your humanity and human spirit truly come through. It’s, it’s a genuine book and I appreciate you taking the time to make that available and accessible to patients.

Dr. Richard Burt: Well, thank you.

Zen Jen: Thank you. I think my only other question for you, which is a way I love to end my podcast episodes, is to ask if there’s anything else you’re grateful for about your experience with HSCT, that has maybe gone unspoken.

Dr. Richard Burt: Well, I guess the number one is, you know, when I started this, it’s just an idea in my mind that didn’t exist in reality. And [00:45:00] to, so to see it come true in reality and to change other people’s lives and to see results that I had always wished for, but you know, you don’t know until you actually do it.

That is a really great experience to have an idea change the world, to realize that what’s in the mind can actually change the structure of the world around you.

Zen Jen: Mmmm.

Dr. Richard Burt: Um, that is, uh, uh, something great. I remember, a friend of mine once told me he was very intelligent, uh, very well educated, but he said he felt like an ant on a leaf in a river stream, just being tossed around with no control over anything.

And I think a lot of people kind of go through life being buffeted by the external environment like that. But, if you have an idea and you can actually change that stream you’re on, with that idea, you realize, [00:46:00] wow, you know, an idea can change reality. It’s a lot of work and you pay a price to do it, but it, it can be done.

And that, that has been very rewarding then, to see how this has affected people and fundamentally changed their lives. And by changing the lives of those people, you, you changed the lives of the, of the people that they interact with. So, that’s been great.

The other great thing is that, you know, you do run into bad people with bad intentions, but you run into plenty of good people with good intentions, and there are good people who have helped me out there, uh, and I’m, you know, very grateful for them.

And I’m finally very grateful for my family, because they paid a tremendous price in my absence for this. And so, um, you know, there are, uh, families that wouldn’t, uh, individuals that wouldn’t tolerate that, but, uh, you know, they paid that price for me to be able to do this. So, all those [00:47:00] things I am grateful for and impressed by, but whenever, I’ve realized whenever there’s a great high, there’s also great low.

Um, and it’s just something you have to deal with. It’s kind of like, you know, if you play it safe and you’re just always kind of steady, you never experience those great highs, you never get to change the world. But if you take those risks and you do that, there are also great lows. There’s kind of for reaction, there’s a, a counter reaction.

And so you really learn to be grateful for those people that are true friends or family that really always want to be there for you. So, uh, I think, you know, it’s made a life worth living and that’s what I tell students. I, I always tell ’em, I say, you know, don’t do, necessarily what other people tell you to do.

Follow your own passion ’cause it’s your life and you have one life. And at the end of the day, if you follow your [00:48:00] passion, whether you win or lose, it’s fulfilled who you are. It’s made your life worth living. And that also means to think for yourself. And I try to bring that out in the book. That’s another level to this, that education, and I’m all for it, but it, it can be, put blinders on you to think a certain way. And what, that’s not really what thinking is. Thinking means, re-thinking concepts.

Zen Jen: Mm-hmm.

Dr. Richard Burt: And questioning them, uh, not in a bad way, but in a good way, uh, to always trying to find, you know, the best way to do things. Or you know, how things really work or what the real truth is, not just to accept the dogma.

Unfortunately, there’s a greater tendency in our academic system that, here’s the dogma, take it and stay with it, and then you get these blinders on. No, the, you know, science is repeating the research, it’s re-searching, it’s questioning the dogma. Uh, [00:49:00] and in the old days, I think science questioned the dogma of religion.

But what science is now failing to do is question its own dogma. And, uh, you know, the, that’s what science really should be and that’s how people should be trained to think, not to be taught how they should think, but trained to think. To question dogma as it, and to, to re-question it. Not in any mean way, but in, in, in to, to retest it, you know, and by doing the, the experiments or the tests yourself is how you learn. Because as information is just shared beyond that, information is lost.

Even when I write a medical paper of the original research, there’s a lot of information there, but in writing that paper, it has to be condensed

Zen Jen: mm-hmm.

Dr. Richard Burt: and certain information is lost, and then when someone reads it, they lose a certain extent of the information, and on and on and on. So, you know, it’s, it’s really the importance of doing it yourself to get the best [00:50:00] understanding of what the actual real knowledge is. And I think that’s being lost. People are being just, uh, in education, spoon fed and you take it this way. No, you know, it’s important to do the research yourself, and that’s where the real knowledge lies. And in questioning the dogma and the academic community. And you’re not taught to do that anymore in, uh, in, uh, academia and, and it’s kind of losing itself that way.

Zen Jen: Such an inspiration. So much there to unpack and carry forward. I think for anyone who’s listening and seeking their own capacity to become their own self-advocate and, question and challenge and dissent from that dogma to gain a better understanding about their options for treatment. And may, may HSCT become more considered as a treatment for [00:51:00] autoimmune diseases.

Dr. Richard Burt: Okay. Well, thank you very much.

Zen Jen: Thank you Dr. Burt. I really appreciate your time and sharing and dedication to being so patient-centric and evidencing for everyone, just your integrity and your fortitude of human spirit that, I’m, going to say is a gold standard for, for life to achieve.

Dr. Richard Burt: Well, thank you. Thank you so much.

Zen Jen: Take good care of yourself. All the best to you in health and wellness, and a lovely retirement. Enjoy every minute of it.

Dr. Richard Burt: Oh no, I haven’t retired.

Zen Jen: I know you’re still, well, you retired from teaching.

Dr. Richard Burt: Well, no, not really. I’m, you know, I’m seeing patients at Scripps and I’m also developing a new IPS technology, which is a whole ‘nother different field. So,

Zen Jen: oh, and that’s a whole ‘nother podcast I would love to have with you

Dr. Richard Burt: down, down the line, that would be another podcast. You’re right.

Zen Jen: I’m, I’m,

Dr. Richard Burt: but no patients can see me at scripts and they can still get these transplants there. [00:52:00]

Zen Jen: Right. Not retired. Still dedicated.

Dr. Richard Burt: Right.

Zen Jen: grateful to you. Enjoy a tremendous rest of the day and weekend.

Dr. Richard Burt: Okay, you too.

Zen Jen: Take good care.

Dr. Richard Burt: Bye-bye.