Using Data to Understand MS

Using Data to Understand MS

Episode 204 – Podcast Transcript

[(0:24)] Stephanie Buxhoeveden: Welcome to the Can Do MS podcast. I’m your host, Stephanie Buxhoeveden. I live with MS and I’m also a clinician and MS researcher. Today, we’re welcoming back Dr. Leorah Freeman, who’s a neurologist and the medical director of the MS and Neuroimmunology Center at University of Texas, Austin. Hi, Leorah. It’s so great to have you back on the podcast.

[(0:44)] Leorah: I always love spending time with you, Stephanie. So thank you for having me back.

[(0:49)] Stephanie: Yeah. Today, we’re going to chat about something a little bit different, which is biomarkers and what biomarkers you’re using right now in your practice, and also how data is helping those of us living with MS every day right now. So let’s start out with what a biomarker is.

[(1:08)] Leorah: Yeah, that’s, that’s, that’s a big question with actually a, an answer that might surprise some people. I know that when, you know, people think about biomarkers, they tend to think, Oh, it’s a blood test, you know, like your A1C for diabetes. But the truth is that, you know, biomarker is not really defined by, you know, how we get to it. You know, it’s really, it’s any measurable indicator of, of a biological process, a disease state, or a response to your treatment. So that can be the clinical measures that we obtained in the clinic, that can be a digital measure, that can be a blood test, that can be an MRI feature. Um, all of those can be biomarkers, but what’s important, the important part that it has to be validated, and it has to show that that measurement tracks with a biological reality that it’s supposed to represent.

[(1:59)] Stephanie: Yeah. And in MS, the best biomarker we’ve had for decades is MRI. And now there is some blood tests, some serum testing you can do as a biomarker. How are you using that in practice today?

[(2:12)] Leorah: Yeah, tha-tha-that’s really interesting. You know, MRI, I, I did my PhD in neuroimaging. I love imaging. I mean, the brain is beautiful. I love looking at MRIs. And I think all of us neuroimmunologists are nerds, and we, we like looking at, at, at the beautiful brains of our patients and, and, uh… But the, the reality about MRI is that we can only get so much. And, and it’s, it’s- there are some aspects that may be hidden that we may not detect fully, uh, with an MRI. So we’ve seen in recent years, the advance in, you know, first in the research space, and then on, you know, the clinical side of, uh, serum biomarkers, so blood tests that help measure some aspects of the biology of MS. Um, you know, so, uh, what you’ve heard the most about is neurofilament light chain, uh, which are, um, you know, which is this kind of blood biomarker that measures, uh, the integrity of axons. And, and then there are some other tests that integrate to NFL, but also look at other protein, uh, such as the MS disease activity test by Octave, uh, that, um, help us understand the activity of the disease. So the influence of peripheral inflammation into the brain and the, uh, the component, uh, of the disease that relates to relapse activity. Um, so that’s the, the latters[?], what we’ve been using in the clinic the past two years. So we’ve been using the Octave test. Uh, and when I first got into it, I was like, you know, the, the evidence was just starting to emerge around this test, but I really wanted to see how it would help me, um, you know, make better decisions and, and how could it help? Who can I layer this on top of what I learned from my patients in the clinic and on top of MRI data? And, uh, it’s been, it’s been very interesting, uh, to, uh, to use this and discover in which clinical context, you know, is, is it valuable?

[(4:04)] Stephanie: Yeah. I’ve definitely used it to see, you know, having new symptoms or I feel like I’m getting worse. My MRI is stable. It’s nice to have an extra blood test that you can use to measure that acute inflammation. Um, the, the longer term progression is harder to track with what we have today. Um, but something that I’ve been using in my own life, I would say in the last six months, um, is I feel like Fitbits and wearables, you know, the aura rings, the watches that they have really come a long way. And I remember, you know, trying to use it and it being very not MS tailored whatsoever. They would just compare me against somebody of my age and, you know, and sex and say, oh man, your heart rate variability is lower than a normal person your age. And that’s not very useful information because I’m not a normal person of my age. Um, and same thing, even my bed yells at me about my sleep and how, and the quality of it. And, you know, it’s hard to explain to an app that’s not personalized. Like, yeah, I have restless legs or I have pain that kept me up at night. Um, so now I have a Google health app that tailors to me and my experience. And it’s helped me discover like where my baseline is heart rate wise, heart rate variability wise. Um, it even gives me this wonderful feedback of like, if I’m on a walk, it’ll tell me, um, when my pace slowed, how far into the walk my pace started slowing and my heart rate and recovery. And so it’s, it’s- For the first time, I feel like this technology is giving me information that I can actually use and adjust. And it’s been super helpful to get that feedback about, um, you know, today your heart rate variability looks good. You’ve got good sleep. Today’s a good day to lift weights, or it gives me signals that, um, it’s saying it might seem like you’re fatigued today. If so, today’s a good yoga day, right? So it’s helping take some of that decision fatigue away. Um, and I’m curious if you’re hearing that or using that in your own life.

[(6:15)] Leorah: Yeah, no, absolutely. I mean, I want to go back to like one point that you made because I think it’s important for our audience to really, uh, understand that is that right now the biomarkers we get in the clinic for MRI and, and serum biomarker are really focused on that relapse biology. So they really help us understand if a disease is active or not active, but it really doesn’t track well with, you know, progression that occurs independent of those acute events or this acute information. So that’s really an important point. Now to your question about, you know, like, I think you were getting into the, the space of like digital biomarkers. Like we all have phones. A lot of us have watches, um, you know, these devices have become omnipresent in our society. And, and so naturally, you know, industry and researchers are just getting into the, how can we use this, you know, all of this data, this information to improve the lives of, of other people through these, these digital, you know, features and biomarkers, you know, I, and I, you know, I have a watch. I, you know, I actually, I do not have MS, but I, I have a condition called dysautonomia where I have a lot of variation in my heart rate and blood pressure, and that leads to a lot of fatigue and what I do and what I don’t do, you know, really kind of, you know, lead to different patterns in, in, in, in how I feel. And, and it’s really important for anyone living with a chronic illness to be empowered to, to, um, adjust, you know, kind of their, their life, pace themselves or just kind of what they do to, uh, you know, based on pattern that they may see in their daily life and identifying these patterns is really hard when you rely on memory. So I think, you know, when we look at the digital space, you know, the first, you know, all of the data that we have, I would not obviously call these biomarkers because they’ve not been validated for people with MS, you know, but they are pieces of information that when used adequately with enough curiosity, but also with enough caution can help, you know, the day-to-day lives of people living with a chronic illness. I mean, of course we don’t want to get into data fatigue, you know, uh, but, um, it can help us identify these patterns that are necessary for us to adapt our lives, uh, to make some decisions regarding our lifestyle. And it can also be beneficial for us as clinicians to identify things that we don’t really see in the clinic room, because let’s face it, the clinic room, like 30 minutes every six months, that’s just a snapshot in an environment that is not the real world.

[(8:54)] Stephanie: Yeah. And I think it’s been a huge help. As you mentioned, there are so many external factors that dictate what symptoms are driving your quality of life at the time. And it’s really helped me better understand the effects that things like sleep and stress and heat and illness are having on my body. Um, and so living with MS or any chronic condition, it can sort of feel random. Uh, you wake up and you never know what you’re going to get, but getting data back to see sort of the patterns and, and take some of that uncertainty away, I think is comforting and helps me adjust my daily routine and optimize it.

[(9:35)] Leorah: Yeah, no, I, absolutely. I think, I think we have to look at it kind of with, with that in mind is it’s, it’s a piece of information that you need to put into the broader context. I don’t, you know, necessarily recommend people to look at their watch and just say, or their ring and be like, Oh, it just told me I’m not ready. So go back to bed. Like let’s analyze, put this into the context of what’s happening in your life. What does your schedule look like these few days? You know, what, uh, how are you feeling, you know, waking up, you know, and put it in that context, but help you, you know, kind of be more informed. I, I love the pattern recognition that we can get from this. I see sometimes people who come to me and just say, well, I, I avoid the heat because I’ve heard that people with MS cannot be in the heat. Well, that’s not true for everyone. I have some people with MS who love the heat, that actually hate the cold. And, um, you know, it’s, you know, with, you know, in science, we tend to look at population-based data and make generalizations based on this. You know, what we want when you’re the one living with a chronic illness is that you want to be able to make decisions based on you. And some of these data that we get from, you know, uh, our, our devices can be, you know, though they are not biomarkers in the true sense of the word where they can really help guide, you know, personalize, you know, our choices and the decisions that we make. And they can also alert clinicians to something that may be happening, you know, with your sleep, for example, like I love looking at sleep data in the clinic. You know, I, I ask people to pull out their, their, their app. And I look at this because let’s face it, sleep apnea is super common in people with MS. We underdiagnose it all the time. It explains over one third of cognitive difficulties in those that live with multiple sclerosis. You know, being able to have something quick that we look at, that’s kind of like a little screening tool. You know, it’s like, oh, your sleep has not been great though you’re in bed for eight hours a day. You know, maybe there’s something there that we need to explore more. And so it invites me to ask more questions. It doesn’t make a prescription, but it invites my curiosity as a doctor.

[(11:51)] Stephanie: I love that. And I think it’s so hard for you as a doctor and me as a patient to understand, you know, what is progression and what is something like sleep that’s fixable. And, and with a little tweaking, we can get you back more towards your normal baseline. Is there a way that this data or another digital biomarker could help us one day more easily pick up on that PIRA, that progression independent of relapse activity, and help us identify maybe when we’ve moved from the relapsing to the more secondary progressive type of MS?

[(12:31)] Leorah: Yeah. I mean, first I want to say that I don’t usually think that people move from one to the other. You know, progression can occur even in people who have relapses. It is often very slow and almost silent and undetected, uh, but it can occur at the same time. You know, when, uh, I think in a conceptualized kind of progression for me, uh, you know, I think that, you know, people with MS, not everybody experiences progression, but you know, not insignificant number of folks do experience that progression. First of all, not all progression is related to MS, okay? And that’s important to hear because as you said, there are some factors that may be fixable. So the first thing that I want to look at is like, you know, what is, what is that, you know… First, is there any progression? You know, usually in the clinic, I might do my walking tests and my neuro exam. That’s probably the least sensitive of all, because again, we’re in this environment where the bar[?] is flat, you’re air conditioned, you’re not stress tested, you know? So, you know, sometimes I make people walk on heels and on toes and in a straight line and, you know, and to try to stress test that gait. You know, sometimes we do some cognitive screening tests and things like that in the clinic, but really, you know, we don’t have a good grasp over what’s happening in between clinic visits. So, you know, first of all, I think that, you know, these kind of different measures, particularly digital measures can, can help, you know, raise the flag. Something’s happening in between clinic visits. Okay. And that things may be called progression if we validate those biomarkers to, you know, align with what we call progression. Then the second question is, is that progression related to MS or not related to MS? And for that, we need kind of multi-layered information. We need some patient reported information, usually kind of PRO questionnaires. You know, we need to, we can look at, um, some of their other data on their phone. You look at sleep, look at, um, you know, environments, look at, you know, different triggers. Some people have more symptoms with certain, you know, food or environmental factors. We need to kind of tease this out. You know, then we like to look at the whole person clinically, you know, it’s like, you know, if the joints have such bad arthritis that you cannot really walk well, well, we may need to fix the joint first before we decide that that progression is truly MS progression, right? So we need to really put that information of like that signal, that red flag that, you know, those digital biomarkers may give us in the future, you know, that this is progression due to MS. Then if we think that progression is due to MS, then, you know, there are really two ways that people accumulate disability in the context of multiple sclerosis. One is in the context of that acute inflammation, what we call relapse associating worsening. So this is due to like the wildfires in the brain and lesion, the contrast enhancing lesions, the disease activity, you know, and we can assess that very well with MRI and with those serum biomarkers I was talking about earlier, like neurofilament life chain or the Octave MS disease activity test, and that can help us make decisions to escalate treatment based on these features, you know. So that would be the first step for me. It’s like, you know, if there’s the wildfires of that inflammation, we need to do something about it before we decide that, you know, this is, there’s a PRA component. Okay? Now we have plenty of patients that are on optimal treatment. They are on say B cell therapy that’s working very effectively. Their biomarkers look great. You know, their MRI is stable, you know, but they’re still declining. We’ve run through, you know, everything that’s, that’s going on, um, you know, in their lives, we’ve optimized sleep, we’ve optimized exercise, we’ve optimized nutrition. We looked at nutritional deficiencies. We’ve treated those, you know, all of those things, right, and they’re still progressing. And that’s, you know, really progression independent of relapse activity or disease activity. And, um, and I think that in the future, what I’d love to have is, is, you know, yes, the digital biomarkers can raise the flag, like something is happening that is progression, but then we’re going to need other biomarkers to tell us that progression is related. Progression biology, which is a different kind of biology than the biology that causes relapses. You know, what we see in progression is really inflammation that occurs within the brain with immune cells that live within the brain that become activated, that sustain that activation. Those are called microglia, for example. Uh, we also see nerve degeneration in the brain and brain atrophy, you know. So we need, we need biomarkers that are readily accessible, that help us relate that signal of, you know, person is progressing to this progression is due to MS to this progression is due to MS progression biology, which occurs behind that blood brain barrier. And we’re not quite there yet, but I would love to see in the future, both imaging biomarkers, but also serum biomarkers like blood biomarkers. That’s just really easy to get in the clinic. And it could be so informative.

[(17:59)] Stephanie: Yeah. And I think we’re getting closer to that being a reality. Um, but you touched on something interesting, which is a lot of times people are on as of today, right now, the optimal therapy. Um, and we don’t have a therapy that really truly gets to the progression yet. We probably will very soon. Um, and at some point, whether it’s progression due to MS or progression due to maybe a little bit of comorbidities and deconditioning, I think that data could help perhaps trigger some referrals out to things like PT, OT, speech that can get you better, right? Even if it is MS progression, um, there’s things that we can do. And I think it’s hard in that 30 minute visit to come up with like a prioritized list of the symptoms that are really impacting quality of life. Um, but I would like to hear your opinion on maybe that triggering referrals to rehab.

[(19:02)] Leora: Yeah, no, it’s a very important point, MS care. And I say this to our trainees all the time. MS care is not just about disease modifying therapy. It is whole person comprehensive care. You know, if you’re, if your clinician is not giving you that whole person perspective, you’re not receiving comprehensive MS. So when I think about my role, you know, yes, I’m keeping an eye on the biology and what treatments may be best, but also I want to hear about my patient’s experience, you know, how they’re dealing with their day to day, what’s happening in their lives, what do they need help with, you know? And I, I feel like, you know, again, like having data layered onto what people recall in the clinic visit can be really important because yes, it’s going to give us some objective measures, um, of, you know, change over time, uh, maybe help identify, you know, like somebody is tired. Well, where does that come from? We can help tease this out with more data and that can trigger referrals, say to a sleep specialist, or if we feel like there’s more of, you know, depression and anxiety that are contributing to that, we can also trigger a referral to a mental health specialist. And, um, so that’s really, really our job and where this, this partnership with our patients is so critical, you know. So, so it- I love some of my patients that, you know, come really prepared for their visits. I don’t want them to obsess over it, you know, but what I’ve seen lately is some folks that are using, you know, either their tools, you know, their, their, their, their apps, you know, to track their symptoms, or some of them are using AI to journal and then get a summary that they can share with me. And, uh, I found that super helpful. I feel, I feel we have to listen to that. We have to be open to that, right? It’s not because those are not validated biomarkers that they’re not useful. And that’s really to fine tune, uh, what a person needs, um, you know, because again, not just meds, you know, comprehensive.

[(21:06)] Stephanie: Yeah. And we’re just scratching the surface, I think, of the potential of these tools. And I know you’re doing some research on actually clinically validated digital biomarkers. And so five to 10 years in the future, what information do you hope an MS clinician will have available when they’re sitting down with their patients?

[(21:26)] Leora: Yeah, I think we’re going to see an explosion of these tools, you know. So I’ve had the pleasure of, uh, being, um, uh, a, uh, principal investigator for studies involving the tool called the MS co-pilot, um, that is a digital tool that, uh, you know- It’s, it’s an active monitoring tool. So people can track different, um, measures related to cognition and walking and vision on the app, but they have to create a session. It’s not passive monitoring when you don’t do anything and it just tracks what you’re, you know, doing in your real world. It’s like an actual kind of, you know, session you create and you measure all these, all of these, um, um, metrics. Uh, but it’s been really, you know, patients that have been part of these studies have found that this is really interesting and useful. Like they, they love the ownership of that information and being able to see, you know, because there’s nothing more gaslighting to patients to feel like they’re getting worse, but then they go to their doctor and doctor tells them, nope, you’re good. You know, so being able to track, you know, over time and have that information, you know, over time has really been something that I think has been validating, affirming, uh, to a lot of our patients and, and also for us, you know, a way of having a window into what happens between clients. And I think, you know, I think that we’re going to see an explosion in the next five to 10 years of some of these tools, some of them active tools that are going to be, you know, really helpful, um, you know, to, to track validated measures and maybe for clinical trials as well. Some of them will be passive tools, which have the ease of like operating in the background and not really asking you to do anything, but just kind of tracking what you’re doing and, and what’s happening in your body. Um, you know, I think that it’s really going to give us that missing piece, which is trajectory, you know?

[(23:18)] Stephanie: Yeah.

[(23:19)] Leorah: Just going from visit to visit is just not enough, you know, but that trajectory, those patterns, you know, and, um, it’s, it’s going to be incredible.

[(23:29)] Stephanie: Yeah. I, I think it’s going to validate a lot of us and what we’ve been saying for decades of like, I know I’m stable, but I do feel worse and it’s, you know, another tool in the tool belt. So I love what you’ve explained about combining these patient reported outcomes with MRI and some of these blood biomarkers that are coming out. And I think it’s, uh, it’s a really exciting time. We’re understanding MS biology more than we ever have before. We’re on the cusp of having treatments that have a bigger impact on progression. Um, we’re living through a huge boon of AI and the capabilities and just starting to scratch the surface there. Um, and I would say, you know, what you talked about, but if your provider is not doing these things, is not discussing your whole life, then you’re not getting comprehensive MS care. So, um, I hope people heard that and know that if they’re perhaps seeing a clinician who’s not talking about these things or who’s not open to discussing the data or anything other than DMT and whether you’re stable or not, that they can find somebody who can provide that comprehensive care to them.

[(24:40)] Leorah: Yeah, no, absolutely. And, you know, another thing that popped to my head as we’re talking is, you know, uh, you know, 70 plus percent of our patients are women. The female body is something magical, okay, but it’s also a pain.

[(24:56)] Stephanie: Yes. [laughs]

[(24:57)] Leora: You know, we go through so much, you know, the ups and downs of cycles, pregnancy, pre-perimenopause and all of these ups and downs and hormones, and then the final hurrah of menopause, you know, it’s, you know, which is only the beginning of the post-menopausal phase. And I feel like this is also a place where, you know, when I’m thinking of my, you know, you know, we’ve been accused of being hysterical women for too long. You know, I feel like there’s also a place for, you know, for this in this digital world that is going to help validate the experience, yes, of all with MS, but also specifically of women with MS who are growing through so much month to month, you know. So, uh, I’m looking forward to that as well. So this is just an aside.

[(25:50)] Stephanie: Yeah. So we will touch base again in a few years and see how things are developing and going ’cause I think this is going to be one of the biggest, um, things that makes an impact on MS care and the way that we understand it. So thank you for being here and talking about it with us today. And it’s always a pleasure to have you.

[(26:09)] Leora: It’s always a pleasure to be here. Thank you so much.

[(26:12)] Stephanie: Thank you. Leora has an amazing sub stack where she discusses this and so many other highly relevant topics. I really encourage you to check it out. It’s theneuroimmunologist.com and we’re going to put a link to it in the description of this podcast. Thank you for listening to this episode of the Can Do MS podcast. If you liked this episode, please leave us a rating and review on Apple podcasts or Spotify. We really appreciate your feedback. We’d also like to thank all of our generous sponsors for their support of this episode of the Can Do MS podcast. Until next time, be well and have a great day.

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