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- [00:00]
A
Hey there. I'm Rachel Feldman and I host a podcast from Popular Science called the Weirdest Thing I Learned this Week. Every other week I circle up with guests like Bill Nye, Josh Gondelman, Mary Roach, and many more to prove that the lofty and noble pursuit of science can also be profoundly weird. From flying Ford Pintos to the world's most illegal cheese, the Weirdest Thing I Learned this Week is the ultimate source for all things interesting, informative, and most importantly, frickin weird. Check out the Weirdest Thing I Learned this Week. Wherever you get your podcast, come on over whenever you're ready to get weird.
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B
Diagnosis matters. Prompt treatment of an acute attack matters because your recovery from that first attack really dictates how you're doing. So recognition quickly and appropriate therapy promptly is absolutely critical. And then preventing further attacks in the right patients with the right medication is what is making a game changing difference in the long term outcome.
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A
For years, some patients diagnosed with multiple sclerosis weren't responding to the typical treatment. They had the symptoms, the care, but no improvements. And then a new discovery changed everything. It turns out they didn't have ms, but a different autoimmune disease one medicine was only beginning to recognize. Today, that disease is known as Mogad, and it's changing how neurologists diagnose, treat and understand autoimmune disease. That's what we're talking about on this episode of tomorrow's Cure for Mayo Clinic, a podcast that brings the future of medicine to the present. I'm Lindsay Sievert. It's great to have you with us. Joining me are Dr. Owen Flanagan, an autoimmune neurologist at Mayo Clinic whose work has helped define how MOGAD is diagnosed and treated, along with Dr. Brenda Banwell, a pediatric neurologist at Johns Hopkins Children's center who has helped shape international diagnostic criteria and brings a critical perspective in how this disease shows up across the lifespan. Dr. Flanagan and Dr. Banwell, it's great to have you both here today.
- [02:08]
B
Great to be here. Thank you.
- [02:10]
C
Excited to be here.
- [02:11]
A
Well, first off, I would just love to know how your work intersects. We were chatting before this show began here and you know each other, you work together, so I'd just love to hear how you know one another.
- [02:23]
B
We met in a number of ways, so we both look after patients with similar diagnoses. So multiple sclerosis, a condition we're going to explain in a minute called moad, and other similar diseases where the immune system attacks the brain, optic nerves to the eye or the spinal cord. And we've collaborated as members of international working groups. We, we've collaborated as friends and colleagues when faced with a patient with a difficult diagnosis. And we want to talk to each other about it. And then Dr. Flanagan is at the Mayo Clinic and has the access into some of the laboratory studies that many of the patients need. And that's always been an incredibly helpful both resource and then a discussion around the interpretation of those critically important results.
- [03:04]
A
Yeah. Dr. Flanagan, when you have such a specialty like mogad, you need colleagues to confer with on the regular.
- [03:12]
C
Yeah, absolutely. And Brenda's been a real leader. You know, she led the way in the MOGAD diagnostic criteria, which was the first real criteria to define the disease as its own distinct entity. And then, you know, she's a great person to run cases by. I occasionally see pediatric age patients, so I'll always ping her for any advice. And then, you know, she always shares interesting cases with us.
- [03:33]
A
Well, wonderful. I'm so happy to hear about your connection. Today we're talking about a disease that forces really, medicine as a whole to ask a really humbling question. Question is, what happens when patients aren't necessarily failing their treatments, but they're being treated for the wrong disease? And so before we get into the science, I want to understand what Mogad is. And Dr. Banwell, you rolled out this very long word, what MOGAD is a little bit ago. So could you, could you start by defining it, Dr. Banwell?
- [04:01]
B
Certainly. So the definition is myelin oligodendrocyte glycoprotein antibody associated disease. What that really means is myelin is the substance that covers the nerves that move from one brain cell to another brain cell, or from one brain cell in the brain down into the spinal cord, and ultimately out to muscles and nerves. And the nerves that are present in the brain and in, within the spinal cord are covered in something called myelin. And myelin is a fatty substance. Think about it as the sort of the black covering of an electrical wire that allows electricity to be conveyed faster along the conduit or in the human body along the nerve pathway. So it's a very important protein, or it's a very important substance which is made up of multiple proteins. And one of those proteins is MOG, or myelin oligodendrocyte glycoprotein. And so if your immune system fails to recognize MOG as belonging to you and therefore attacks it as if it was a virus or a bacterium or a foreign cell, then it can destroy or damage this important substance called myelin, and that leads to neurological problems in the brain, nerve to the eye or spinal cord. And in this context, it is the antibody, which is an immune protein, that is attacking mog, and that leads to the MOG associated disease, or MOG antibody associated disease we much happily refer to as mogad.
- [05:34]
A
The discovery was the result of scientists around the world building on one another's research. Among them a colleague, Dr. Kevin O', Connor, a neuroimmunologist whose work helped establish that MOG antibodies pointed to a disease different than Ms. Dr. O' Connor's research helped show that antibodies targeting a protein called MOG weren't simply associated with Ms. Instead, they identified a distinct autoimmune disease, one that would eventually become known as Mogad. Dr. Flanagan, in your work, this has been sort of a lesser known autoimmune disease, mogad, that is getting now more recognition because it can often be confused or intersect with some of the symptoms of ms, Is that correct?
- [06:19]
C
Yeah, I suppose the disease was initially recognized. Initially, it was thought that the myelin antibodies or the MOG antibodies might be a marker of multiple sclerosis, which is the most common demyelinating disease in the central nervous system. And then many years ago, Kevin o' Connor led a group that showed that antibodies to MOG defined a different condition in which pediatrics was overrepresented. They account for a quarter to a third of cases of mogad, and patients tend to have more optic nerve involvement than eye involvement. So once this discovery was made at the Mayo Clinic, we developed an antibody to mog, a live cell based antibody that we can test for patients and then that can give us a result that can tell us what the patient potentially has. So that was. We used techniques that we had used for a similar condition called neuromyelitis optica spectrum disorder, where there's an antibody to a water channel within the brain that causes similar symptoms. So luckily, we had had previous experience with developing that antibody and we were able to apply the same techniques to this condition and then make the antibody tests widely available. And now it's being used right across the world to diagnose this condition. In Europe, Australia, in Asia, and even in some countries in Africa, it is available.
- [07:35]
B
So I think, you know, my team, who, I mean, I'm a pediatric neurologist, so I see children with neuroimmune diseases of the brain, optic nerve and spine. And just like my adult colleagues, we all realized we were seeing patients who came in with symptoms as you Said that look like multiple sclerosis?
- [07:52]
A
A little.
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B
But whose disease course and MRI features and then even some of the ways they were recovering from a specific immune attack differed from what we were typically seeing in multiple sclerosis. And then once we were able to bring together samples from a group of children and adults with classic multiple sclerosis, and then a group of children and adults with what we thought was this different looking condition, we, we were able to identify that the people with this relapsing inflammatory disease, or children with a form of what we call acute disseminated encephalomyelitis, or adem, had these antibodies to mog, and that they were indeed a different group of patients from those with multiple sclerosis.
- [08:35]
A
What was the time period when you started realizing that these symptoms were something else?
- [08:39]
B
You know, I personally started recognizing this about 2004, but others predated me. That's when I had enough experience in looking after children. I started a program for children with what might be multiple sclerosis or related conditions in 1999 and had a large Canadian study in partnership with some amazing colleagues. And I think, you know, by that point, five years into that program, we realized that we had a subgroup of children with multiple sclerosis, a subgroup with a single event that didn't go on to have chronic disease, and then a subgroup of children with this, you know, Ms. Like relapsing condition, but with very unique features. And so it took a long time to get to the 2023 diagnostic criteria, because when you recognize a group of patients, you then have to be sure you're seeing something that others also identify. And then we had to work with Dr. O' Connor and then subsequently with the Mayo Clinic and also with the group in Oxford and the group in Japan to identify tests to identify MOG antibodies and to apply them consistently, and then ultimately to come together as a community to create diagnostic criteria for this condition we call MOGAD.
- [09:47]
A
What Dr. Banwell is referring to are the internationally accepted diagnostic criteria for Mogad, published in 2023. After nearly 20 years of research and collaboration with experts around the world, they gave physicians something they never had before, a shared playbook for diagnosing mogad. Rather than relying on one blood test alone, doctors look at the whole picture, including a patient's symptoms, MRI findings, and antibody testing to determine whether MOGAD is truly the right diagnosis. I'm just curious what that moment is like, when you think you've been treating Ms. And there's another disease possibly revealed that you didn't know about. And in some ways it has to feel. I was thinking maybe your heart drops like we've been getting this wrong in another way. It's exciting to give informations to patients that really need it.
- [10:40]
B
I can. Cause I remember my first five patients like it was yesterday. The first five children that were entrusted into my care in this demyelinating program and I didn't have an answer to any of their parents questions. Why did this happen to my child? Did we do anything as parents nutritionally or exposures or anything that might have contributed to why my child has had this attack of the immune system in the brain and spinal cord and optic nerves? Is this a lifelong condition? What does it mean for my child's future? It's a pretty humbling moment when you don't have those answers as a clinician because the condition hasn't been described before and you realize that these kids don't look like the children with multiple sclerosis, which even then was a very rarely utilized diagnosis in pediatrics. There was still a lot of work to recognize multiple sclerosis in children at that time, but this group were clearly different, but yet we didn't even have a name for it. And you know, you have to be humble. You, you tell people the truth. You know, I, I, I can see that your child has a serious issue. Here's what we can do today. And we were really fortunate and honestly, I think pivotally, and I'll give full credit to every single child and teenager and their parents who agreed to sign up for a study that went on all the way through till the pandemic, where they provided blood samples and DNA samples. They allowed us to image their brain as they would need clinically, but then to retain those images, to put it all together even when they were feeling great. So, you know, that's what it takes to identify patients with different diagnoses. And it is a celebration when you can give them a better answer to say, I now know what it was that I couldn't answer in 2003 or 2004.
- [12:18]
A
Thank you for sharing that. It's a beautiful moment in discovery that laid the groundwork for where we are today. And Dr. Flanagan, I'm wondering if you had a similar watershed moment where MOGAD came to your clinician practices and your consciousness as a doctor.
- [12:35]
C
Yeah, I suppose as I was starting out as a junior faculty member, MOG was just coming on the scene and was a really exciting time. There had just been this other discovery of Aquaporin 4 antibodies, a marker of neuromyelitis, optica spectrum disorder. And it looked like this new condition had very characteristic features and very different to multiple sclerosis in many ways. So that, you know, led me to kind of pursue that as an area of interest. And I've had great mentors here. Dr. Pittock and Dr. Luconetti had guided me. And I was supported by the NIH at one of the earliest grants on MOG antibody associated disease. So then I was able to kind of lead off a career in research. And like Brenda mentioned, having patients contribute to that has been really amazing. And I will say, you know, it's really impactful for patients when they can get a diagnosis, a true diagnosis. You know, we've had some patients come into us who have had Mogad for 40 years, since they were a child, and they were told they didn't know what they had. You don't have multiple sclerosis. You have some unusual condition and we can't define it. And one of those patients came to us and we were able to identify the MOG antibody. And really it was life changing for them to have an actual diagnosis and an identity.
- [13:44]
A
So I'm wondering if you could each expand on what that is and how that is sort of the gold standard in getting on the right path for diagnosis and treatment.
- [13:52]
C
Yeah, I think it is. You know, it was a group of 20 or 30 individuals who came together and we kind of from all around the world, a very diverse group of people. And the diagnostic criteria, I suppose, is split into three major parts. The first part is the clinical syndrome. So those symptoms that we mentioned, optic nerve inflammation, so vision loss, spinal cord inflammation causing paralysis, weakness or bowel or bladder trouble, and then brain involvement causing a variety of different syndromes of confusion, seizures, potentially coma, double vision or imbalance. So you have to have that typical clinical syndrome. And then the second part is having the MOG antibody test. The MOG antibody test is a little bit sticky. So some people who don't have MOGAD can have a low level of antibody. So when the antibody level is low, we require some additional criteria, which is our feature is generally on the MRI or on the clinical examination that are more suggestive of MOGAD than other conditions. So because of that stickiness in the antibody, we require people to have. But when the antibody is super high, then really that makes the diagnosis very likely when the antibody is strongly positive. And in that situation, you just need to go through a final step to make sure that your diagnosis is correct. We do this in medicine all the time, where anytime a test result comes back, we kind of put it into context. Does that fit with the overall syndrome? And then there's another mimicking condition called neuromyelitis optica spectrum disorder, where when the antibody is low, we should also make sure that that test is negative. So there's three steps, I suppose, to the diagnosis. The first is the clinical symptoms. The second is having a positive MOG antibody. And if it's a high positive, then the third step is going to be just making sure that that's the correct diagnosis. And if it's a low positive, you're going to require some additional features on examination or on MRI that are consistent and then going through that final step of making sure that there's no better diagnosis.
- [15:49]
B
The reason we have diagnostic criteria is to help guide a clinician, an experienced person sitting with a family, with a patient, talking through what they've experienced, making sure that their symptoms and the findings on exam align with symptoms that we recognize as being optic nerve inflammation or brain inflammation or spinal cord inflammation and not something else. And that does require really listening carefully and doing a very careful examination and then interpreting the results of a test. So a positive test alone is never enough. You need to put that, as was mentioned, into the context of the clinical story, because any test can have what's called a false positive. And then importantly in any diagnosis is the humbling reality is could there be another, better explanation?
- [16:36]
C
The Wired newsroom is known for award
- [16:38]
A
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C
On WIRED's Uncanny Valley, we take that curiosity even further. Each week, journalists from Wired break down the biggest stories in tech while speaking
- [16:48]
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C
Building, challenging and reshaping the future. Is the AI boom sustainable? How do you protect your privacy in an age of constant surveillance? Uncanny Valley tackles the question driving today's tech debates and lighting up your group chats.
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Listen to new episodes every Thursday.
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C
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C
Find Mayo Clinic talks on your favorite podcasting app or visit ce mayo.edu podcasts to learn more. Every week we share succinct, relevant and practical medical insights tailored for healthcare clinicians that you can immediately apply to your practice.
- [17:38]
A
Each episode covers common health issues seen
- [17:41]
C
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- [17:51]
A
I imagine there's so many patients out there that struggle from autoimmune conditions that are being discovered in real time every day. Dr. Flanagan, I'm wondering just to follow up on that, if you could sort of stack Up Ms. Symptoms against MOGAD symptoms side by side where they're similar and where they delineate.
- [18:09]
C
Yeah, absolutely. So I think in terms of some of the symptoms, some overlapping symptoms. So with the vision issues, where, as Brenda mentioned, the conduction along the nerve is not quite as good as we would like to, people can present with pain with moving their eye and vision loss with mogad oftentimes in up to half of patients that can be in both eyes and very severe. So patients can come in where they develop blindness very quickly. With multiple sclerosis it tends to be a little bit milder. So patients will describe having blurred vision, not being able to see and some pain in the eye, but they're generally not completely blind in both eyes, which is a common future of mogad. And similarly with involvement in the spinal cord, again, patients can have numbness, they can have weakness, and they can have some difficulties with their bowels and bladders, but the MOGAD episodes tend to be more severe. So people will come in where they're not able to walk despite their spinal cord involvement, while Ms. Patients may come in, they're walking, but they have numbness and they have a little bit of imbalance, but they tend not to present where they're not able to walk at all. So the MOGAD patients tend to present a bit more severely and they often will present to the hospital with these symptoms and then we have to bring them into the hospital. And lastly, MOGAD tends to involve the brain and cause more confusion and seizures than does multiple sclerosis. So particularly in young children, they can present with new onset confusion, episodic seizures or epilepsy type presentations. And some of those presentations can be very severe. And Brenda's done some work on this where patients will present at the icu, they have increased intracranial pressure and they really need life saving neurosurgical procedures to save them. We don't tend to see that as much in multiple sclerosis, so that tends to be more frequent with Mogad.
- [19:58]
A
And then Dr. Banwell, does Mogad show up more in children than Ms. Does? Or could you talk about the early recognition that you were seeing in children which led to this discovery?
- [20:11]
B
I think the first thing to comment on is, as you just heard, is that the first attack of multiple sclerosis, mogad, or what we call a monophasic single attack, one event, one phase demyelination, can look very similar. And our job is to try to then predict the future and identify whether this is Indeed, the first event of a chronic illness or a one time attack. And of course, at that precise moment, treat that first attack for what it is, which is an emergency, and move forward from there. So I think the first step is the immediate management of the patient in front of you and then predicting what outcome is coming next in terms of the likelihood of further events. And that's where the diagnostic criteria have played such an important role in multiple sclerosis, MOGAD and other conditions, where specific findings can help guide you on which disease you are most likely dealing with. Even before the blood test comes back and confirms the MOG antibodies.
- [21:06]
A
As you were talking this through, I was just thinking about the stakes being so high to get it right. I mean, these are sound like agonizing symptoms, especially for the small children, you know, blindness, inability to walk, confusion, you have frantic parents or adults that are in pain and you're about to give a life altering diagnosis. And I can imagine the weight on your shoulders to make sure it's right. Whether it's MOCAD or Ms. That responsibility
- [21:34]
B
is, you know, part of the Hippocratic oath. You take at your white coat ceremony the first week of med school where you, you, you know, pause and reflect to say, am I ready for this responsibility? And it never goes away. And it's also, it's, it's the greatest privilege, but it's an enormous responsibility. And that responsibility is daily because it can be. You know, one of the things as a clinician is you always have to be vigilant that you don't get too lulled into thinking this is the next patient with the diagnosis that I made and the three before them. And that's the joy, I think for me and the challenge in medicine. But it's also a dialogue. It is what you share with a family as they come to you looking for your expertise. And as an expert in any area, part of your responsibility is to confer a diagnosis when you're confident that the person meets the criteria that have been so carefully put forward, but also to have the courage to say, I don't think that's what you have.
- [22:26]
C
And I think sticking with the theme, you know, we're stronger together, you know, so we often work closely with our colleagues. So I think similar to the themes earlier of discovery, you know, we're stronger when we work together. And you know, I think at large centers we have a, we're lucky to have that, those multidisciplinary teams that can really help people. We have a MOGAD clinic and we had the opportunity to have a MOGAD patient day where we were able to bring people on site. And both Brenda and myself have been partnering with the MOG project, which is a group that will often have patients who are, you know, are not as well served with experts in demyelinating disease or neuroinflammation. So they will send us patients, and we'll try and bring them in quickly and get them looked after very quickly. I know Brenda said some in her region, We've had some in our region. So it's really a partnership and stronger together to get the patients where they need to go, get them the right answer. And then a lot of times, once you have the right diagnosis, it's a little bit easier in terms of the treatment plan, and we can transition those patients back to their local community with an answer for what their symptoms were being caused by.
- [23:31]
B
The other thing that is important to comment on is, in addition to looking for MOG antibodies, which define the disease, there's also been important research done in Korea and other countries in North America looking at, you know, what are the other proteins that the abnormal immune system in children with mogad, in this case, make. And so one of those proteins is something called interleukin 6, which say cytokine. Nobody has to remember all of that, but it's an immune protein that can be elevated quite significantly in the spinal fluid in patients with mogad. And we recognize this or this. The, you know, people that have started that research recognize this finding. And that has been really important because increased interleukin 6 is also seen in neuromyelitis spectrum optica disease. And a treatment where you block Interleukin 6 effectively has been very important in the treatment strategy for neuromyelitis optica spectrum disorder.
- [24:29]
A
One of the most exciting discoveries was another clue. Researchers found that many people with mogad have elevated levels of a protein called IL6, an important messenger in the immune system. That finding pointed to something even more promising. Existing medications that block IL6 were already helping patients with other autoimmune diseases, opening the door to testing those same therapies. With MOGAD. The question was no longer whether IL6 played a role in MOGAD. It was whether blocking it could prevent future attacks.
- [25:01]
C
I think it's a really exciting area of study. You know, Interleukin 6, the way I think of it as a simple way, is kind of like it's the fuel for your immune system, and it controls a little bit the blood brain barrier. So that leakage of immune cells into your nervous system. And similar to our experience from other conditions, this treatment has seemed to work well in those other conditions. So now we use it a lot off label or we don't have a proven treatment, but there is a clinical trial of a treatment called satralizumab, which was just presented and looks like it is effective at preventing relapses. So we were part of the clinical trial here at Mayo Clinic. We had a number of patients in the trial and they would come every few weeks for their dosing and we would evaluate them. And I think, you know, the investment that pharma has put into these conditions has really been helpful to kind of drive the field forward and perform these what we call placebo controlled trials. And interleukin 6 blocking treatment has been used for other conditions in neurology in the form of inflammation of some of the arteries called temporal arteritis. And then it's been used in rheumatology for treatment of rheumatoid arthritis. So the treatment pathway is available all around the world. So this means that if we can show that these medications are effective, we may have a treatment that's already available around the world. And so that's a really exciting as a type of pathway that we can target and something that can be scalable around the world and potentially affordable. It's available now in biosimilars. So it's really a medication that we can that can be utilized around the world. So that's one of the exciting parts of it.
- [26:36]
B
The fact that that protein is very high in the spinal fluid led my group and others to use a medication that blocks interleukin 6 receptor in patients with life threatening MOGAD children who presented with brain swelling, without doubt heading potentially to death, frankly. And so that discovery isn't because of the MOG antibody. That's a ongoing partnership to recognize aspects of what I call the immune signature that tell us what happens in the condition, but that can still shed light on therapeutic, important discoveries.
- [27:12]
A
I would love to hear Dr. Flanagan a little bit more about the MOG clinic at Mayo Clinic.
- [27:16]
C
Yeah, so, yeah, we have a MOGAD multidisciplinary clinic where we, you know, have patients who come in, they see us, they see our neuro ophthalmologists, and then depending on their needs, they will see neuropsychologists, urologists and other multidisciplinary specialists. And really we kind of fast track those appointments. So if people are in need, you know, sometimes the MOG project for Example, the patient organization will reach out. We'll have an urgent request. We bring those patients in and get them seen by everybody across the group. And then, you know, we work together. We'll discuss as a group what the best plan is for those patients and what's their best treatment plan. Some other areas we're interested in is some of the MRI findings. MOG has a really great propensity for recovery, but it sometimes needs help, like Brenda mentioned, to get through that acute episode. But the lesions in MOGAD actually tend to disappear. So the white matter changes in MOGAD disappear, and that's different to multiple sclerosis. The term multiple sclerosis means multiple scars, and multiple sclerosis tends to leave a lot of scars along the nervous system and spinal cord. And that leads to later problems. You know, in people 10, 20 years after diagnosis, they can get slow, gradual deterioration that we term secondary progressive disease. And we don't really tend to see that with, with mogad. Now, those episodes are still consequential, and we need to treat them very aggressively. But these patients have a phenomenal ability to recover. So the key message, I suppose, is in a patient who presents to you with a MOGAD episode who's having a severe attack, they need to be treated really aggressively to get through that episode, get the optimal recovery. And particularly in those children who can have those life threatening episodes, we really need to do all that we can because we know if we can get them through the episode, they can recover, go on and do very well over time. So it's really important that we're treating them aggressively and we do some studies looking at some of those MRI features, some of those disappearing lesions, and that can be helpful both to make sure you're on the right track with diagnosis and help us understand what's happening. You know, is there some remyelination or are they able to better put the myelin back on the nerve that can recover better. So we're not sure of all the mechanisms yet, but we're trying to learn more as that might have implications for some of those other conditions where those scars form. And is there ways that we could learn about this that could help people with multiple sclerosis?
- [29:33]
A
So you're saying that Ms. Has a tendency to leave more of those scars or lesions where mogad, not as much.
- [29:40]
C
Correct? Yeah, the mogad. Sometimes people describe it as vanishing lesions or disappearing lesions. About 70 to 80% of the brain lesions or spinal cord lesions will disappear in mogad. So that's A real signature that it's very different. It was probably some of the early clues for Brenda that this was a different condition than multiple sclerosis.
- [29:58]
A
All this groundbreaking work and these therapies are underway at your Mogad Clinic. And I was just kind of. I wanted you to sort of reflect on the patients that are coming to you and sort of the community that you speak up.
- [30:09]
C
So some people have come to us and they've had other problems. You know, we had a patient recently sent to us from the MOG project, and this person had a spinal cord problem, and it was thought to be mogad. It would get better with this treatment of washing out their antibodies, and it would get worse with steroids. But it turned out actually that they had an abnormal connection between their artery and their nerves. So we, when we saw the images, when they sent them over, we said, you need to get to Mayo Clinic emergently. So they came within three days. We brought them in. We had them see our neurosurgeon the day after they saw us in the Mogad Clinic, and they were able to diagnose the condition and treat it at the time of an angiogram. So the Mogad Clinic, we still see some patients who don't actually have mogad, and we can get them on the right track with their own condition. And then for other patients who are coming in, it's been really helpful for us to recruit to those clinical trials. We've had people from all from many different states around the southern states in our clinical trials who are flying up once a week for many weeks from many hours away of flight travel. And patients have put in this huge amount of effort just to participate in these trials. And they're not just doing it for themselves as a potential benefit for themselves, but they know that these clinical trials, if they're successful, could treat thousands or tens of thousands of patients down the line for many years to come. So it's been a real joy to get those patients in. And the patients who've been applicable and interested in clinical trials, we've been able to enroll them.
- [31:37]
A
Clinical trials are the bridge between discovery and patient care. They help physicians learn what works, what doesn't, and which treatments hold the most promise. Those answers don't just advance science. They begin to shape what the future looks like for people living with mogad.
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Hey, Ira Plato here from Science Friday. Each episode, we give you surprising facts.
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Facts. There's a whole phenomenon of moths visiting eyes of mammals.
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From space to climate to tech to medicine, get a new view on the world around you. That's Science Friday. Wherever you get your podcasts.
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AI is everywhere, and so is the noise around it.
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- [32:52]
B
so I would say the overall prognosis in mogad, we're still learning because unlike multiple sclerosis, we don't really have 50 to 100 years worth of described history. We have a very long history in multiple sclerosis dating back to Charcot and early scientists. But I think in moad, which has been characterized more recently, most of us have the ability to go back in time to blood samples that we stored with family's permission from when they first came in. So, for example, back in the late 1990s in my case, and then run those samples to see if they had MOG antibodies way back then. And I'm making this point because, first of all, that allowed us to say what was happening at the time that this person first presented? Did they have MOG antibodies? And the thing about MOG antibodies is that we haven't mentioned right now is that you can be MOG antibody positive when you first come in, but over time the antibodies can go down in amount such that they're no longer detected in blood. And that's really important because if you meet someone three, four years later, the blood test could be negative. But that doesn't mean that their story is not mogad. It means that they may have had a single attack of MOGAD five years ago, but you missed the chance to look for those MOG antibodies. The blood test, too far out is no longer positive. So that's important. And we've all learned that lesson. Similarly, as just mentioned, when you look at the MRI in a person with MOGAD, as Dr. Flanagan just said, the inflammatory changes that are present at the beginning can resolve over time, which is totally the opposite of what happens in multiple sclerosis, where those changes keep coming and increasing over time. So if you look at an MRI two or three years later, they don't look very similar at all patients with multiple sclerosis have acquired all these silent new spots in the brain or spine that are inflammatory and scarring. And then patients with MOGET are not now, very happily, in both pediatric multiple sclerosis and adult multiple sclerosis patients, there are now very highly effective therapies that we are using right from the beginning. And I make that point because if anyone's listening to this podcast who has multiple sclerosis or a loved one with multiple sclerosis, the highly effective new therapies are changing what I just said and they are blocking and effectively turning down the abnormal immune response in multiple sclerosis. And my pediatric multiple sclerosis patients now on highly effective therapy are not acquiring multiple new brain lesions over time. They are actually doing incredibly well. So with the appropriate diagnosis and appropriate therapy in multiple sclerosis and in Mogad and in Aquaporin4, disease patients are doing vastly differently than if we were to tell this story 20 years ago. So message of hope to all on this call is that, you know, diagnosis matters, prompt treatment of an acute attack matters because your recovery from that first attack really dictates how you're doing. So recognition quickly and appropriate therapy promptly is absolutely critical. And then preventing further attacks in the right patients with the right medication is what is making a game changing difference in the long term outcome. So most of my patients, my entire army of patients, whether that be multiple sclerosis, MOGAD or others, were to parade in to say hello, you would not know that they have any of these conditions. In the majority, I have one or two children whose recovery has not been complete. And that's definitely true. There are, there are patients that have a severe first event and do not enjoy a full recovery despite everything we do to try to achieve that. But the vast majority of children with MOGAD and the vast majority of children and teenagers with multiple sclerosis in today's world are currently doing extremely well.
- [36:37]
C
Treatments in the MOGAD area are only just emerging. I suppose we're far behind. You know, multiple sclerosis has maybe 25 different treatments approved treatments. Aquaporin 4 has four or five approved treatments, depending on the different region. And a mogad, we still don't have an approved treatment, but clinical trials have been started and we're applying those diagnostic criteria, which was the first step. And now they're starting to read out and are looking like they're going to be positive. So I think we've got some really exciting news ahead and I would echo the hope out there. For our patients that we're going to have even better treatments over the next one to two years. We'll have more available treatments that will really better be able to treat our MOGAD patients, particularly those that need it, that have that more relapsing course or more severe course than just a one off episode.
- [37:23]
B
The other very important thing we all do as experts and colleagues is that we write international consensus diagnostic programs and what we call algorithms or strategies. And even before a formal trial is completed, we publish and share what we feel would be appropriate, rational treatment strategy, which we use across many, many, many, many clinics. So we've been treating patients with MOGAD with various protocols that we do believe are effective. But the best way to really know if something is absolutely optimal is to have a formal clinical trial where you compare a new treatment to a standard therapy in most cases now to see, you know, which is better and why and for whom. Because that answer might not be the same for every person. And I think the, you know, the study of therapy and understanding why a treatment works and why it doesn't, or why it worked better in one group of patients versus somebody else, that's how we end up with effective strategies down the road. So all of that is happening in the MOGAD world, which is really exciting to see. It's been incredibly humbling and truly exhilarating to see the difference in outcome in persons living with Ms. Over the last two to three decades. It's a completely different conversation with patients now. So all of this matters that we want to treat our whole community, not just those newly diagnosed, but also those who've lived with any of these conditions for years, or even in the case of multiple sclerosis, decades.
- [38:54]
A
What sounds so promising is that this isn't just the story of one diagnosis or two diagnoses, that it really opens up a potential future path for treating so many diseases known and maybe currently unknown.
- [39:08]
B
I think that's right. And I think, you know, cancer chemotherapy is a good illustration of this concept where, you know, most individuals who are diagnosed with cancer are entered into a protocol, right. It's not just what does your doctor wish to prescribe for you, it's what are the international cancer consensus treatment guidelines for whatever type of cancer that you have. And that has dramatically improved the outcome for persons with cancer. Because no one person knows the exact answer for which medication is the best one for a given cancer patient. And often it's not only one medication in the cancer situation. It's often a combination of medications that work on different parts of the cancer pathway. And so that concept, that ability to say, let's design this together and let's have a consensus and then we're going to revise and change protocols for the right reasons is really how we get care moving forward. And clinical trials, as Dr. Flanagan just mentioned, where you compare a medication either to a second medication or just give the medication to half the study group with a rescue plan that if the people who are not receiving the medication need something to be done, they have an off ramp, of course, to keep them safe. But, but, you know, these are how these studies are essential to answering the question of what works. And then also invariably we start to identify, you know, as you said, the fire or the fuel for the immune system in the case of interleukin 6 or other pathways that ultimately do guide us for therapies for other diseases, that is absolutely what happens next. And we just keep moving that forward.
- [40:44]
C
And I think we're moving more towards, you know, precision treatments. You know, historically for the example in chemotherapy of cancer, you know, we would broadly hit, you know, people with very severe side effects from really hard hitting chemotherapy. And now in cancer and similarly in immunology, we're targeting small molecules in the nervous system where the treatments are much more tolerable.
- [41:04]
A
Sounds like a robust and passionate community, not just for you as doctors that are uniting in this front, but for the patients themselves that know that they're on the cusp or a new frontier of the disease that they suffer from. I just wanted to say if I am that patient, putting myself in their shoes, I am so heartened that there are Dr. Banwell's and Dr. Flanagan's meeting around the clock. And I just, I thank you both for your dedication to understanding this disease and for educating people on the differences between MOGAD and Ms. Just really thank you.
- [41:35]
B
Totally our pleasure. And thank you for having me.
- [41:37]
C
Thanks so much. It's been a real pleasure and great to partner with Brenda on the this
- [41:41]
A
Tomorrow's Cure is a production of Mayo Clinic with production help from the podglomerate. Be sure to follow Tomorrow's Cure wherever you get your podcasts and if you like today's episode, please like and subscribe. I'm Lindsay Siebert. Thank you so much for being with us.