Today, we present an exclusive interview with Jonas Bergquist, MD, PhD, from the OMF Collaborative Center at Uppsala, who shares insights on neuroinflammatory involvement in ME/CFS.
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The Heart of the Matter
- Neuroinflammation, altered cerebral blood, and dysregulated hormones have all been separately observed in ME/CFS in prior research.
- Dr. Armstrong and his team at OMF’s Melbourne ME/CFS Collaboration have designed a study to examine the link between these three observations in people with ME/CFS, Long COVID, and POTS.
- The study will use MRI and PET imaging, blood draws, and surveys to characterize neuroinflammation, cerebral blood flow, and hormone levels.
- The project is currently under ethics review and therefore in the “Study Design, IRB/Ethics Review” stage.
Neuroinflammation, problems with cerebral blood flow, and hormone dysregulation have been observed in ME/CFS and Long COVID through previous research, but these components are rarely studied together. Dr. Chris Armstrong, the Director of Open Medicine Foundation’s Melbourne ME/CFS Collaboration, and his team have therefore designed a study to investigate whether issues with cerebral blood flow and neuroinflammation are impacting the hypothalamus-pituitary-adrenal (HPA) axis and contributing to the dysregulation of hormones.
Through this study, Dr. Armstrong’s team is testing their hypothesis that there is an alteration in glutamate receptors that correlates with the dysregulated hormones that are measured in the periphery. Part of their study design, therefore, includes magnetic resonance spectroscopy (MRS) to look at metabolite levels and neurotransmitters, including glutamate, in the hypothalamus region of the brain.
In addition to MRS evaluation of metabolite levels, the study team will also use magnetic resonance imaging (MRI) and positron emission tomography (PET) techniques to measure blood flow through the brain and neuroinflammation. One unique aspect of the imaging techniques the team will use is the tracer marking astroglia cells as a measure of neuroinflammation, which hasn’t been used previously in ME/CFS and Long COVID. Ultimately, these imaging data will also be combined with survey data and analysis from blood draws.
To facilitate the detection of a link between neuroinflammation, cerebral blood flow, and hormone dysregulation, this study will incorporate a small exertion via a hand grip strength exercise. The team will take scans before, during, and after this exertion, and collect blood before and after to look at any deficits in cerebral blood flow, changes in metabolites in the hypothalamus region, and changes in hormone levels in the blood. Ultimately, this project may help with understanding biological pathways contributing to ME/CFS and Long COVID.
Dr. Armstrong’s imaging study is currently in the later phases of ethics review, part of the “Study Design, IRB/Ethics Review” stage of the research process.
Dr. Armstrong has successfully secured a grant from the US Department of Defense for this project. This achievement underscores the exceptional quality of Chris’s work in a highly competitive grants round, where only 10% of ME/CFS applications were funded.
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Video Transcript
Dr. Meadows: Hi everyone, and welcome to another interview with one of our esteemed directors. This is the last in our series with our international colleagues. So that, of course, means we’re talking to our Melbourne ME/CFS Collaboration today. So, I’m really happy to be joined by Dr. Chris Armstrong.
In brief, Doctor Armstrong’s center aims to decipher the common biological pathways found in ME/CFS, with kind of an emphasis on metabolic studies and precision medicine. So welcome, Dr. Armstrong.
Dr. Armstrong: Thank you very much for that kind introduction, Danielle. And thank you to everyone listening and spending time to be caught up on this project we want to talk about today.
Dr. Meadows: All right, and speaking of that project we want to talk about today, we’re going to chat about one of your newer studies using PET and MRI imaging in ME/CFS, POTS and Long COVID. So, to start us out, can you just give a short overview of the rationale for performing this study and kind of what the study design looks like?
Dr. Armstrong: Sure! So, there was a couple of reasons why this study kind of came to be. We’re interested in cerebral blood flow in this population and we’re interested in, obviously, neuroinflammation, which has been highlighted by a number of different groups around the world.
And at the same time, we’ve noted that there is this potential HPA axis involvement in this disease. And so what that is, is the hypothalamus, which is an almond size piece within your brain, actually controls or produces a lot of major hormones throughout your body. And these hormones have been highlighted to be somewhat different in ME/CFS and Long COVID as well.
So, we wanted to know if that particular blood flow or neuroinflammation issues were also impacting the hypothalamus region and therefore may be contributing to this dysregulation of hormones that we see.
Dr. Meadows: That’s awesome. In the spirit of OMF’s collaborative research design, we heard last week from Dr. Bergquist about how he’s using MRI and PET imaging to study neuroinflammation and microglia activity. Can you comment maybe on how this study complements that work and what’s unique about this study compared to that?
Dr. Armstrong: Sure. So our study design is quite different. So we are looking for neuroinflammation marker, and I think the study in Uppsala is looking at TSPO, whereas we’re looking at a tracer that’s called SMBT-1. And so this tracer that we’re looking at is actually looking for markers of neuroinflammation on a different type of cell type. It’s not looking at microglia, it’s actually looking at astroglia.
And so it’s looking for neuroinflammation markers that are existing on the astroglia themselves. And this has never been done before or followed before in Long COVID or ME/CFS. This is a different type of neuroinflammation marker.
At the same time, we’re also looking at MRS. So, we’re looking for metabolites, levels in the brain, specifically around the region of the hypothalamus, so that we can highlight whether we’re seeing elevations of neurotransmitters, things like glutamate, that may be somewhat related to altered regulation of the hypothalamus.
And then we’re also targeting the idea of blood flow itself. So we’re doing a tracer of blood flow through the brain for this population. So, there are some similarities to the Uppsala project, and there are some differences. So we’ll be able to validate, in some aspects two different cohorts, and at the same time, we’ll be able to show some very different things in these different populations.
Dr. Meadows: That’s awesome. Thank you. Can you talk a little bit about your hypothesis or what you might expect to find from your study, and how might results from the study translate to the clinic in the future?
Dr. Armstrong: So the hypothesis about this study is actually, we have a few different ideas, but the driving force with this project is actually a PhD student Ellen, and she actually has a strong hypothesis in regards to glutamate and its role. So she’s really highlighting the idea that there’s this alteration in glutamate receptors and is interested in the role that maybe this glutamate is playing.
And so what they’ll be targeting is measuring that glutamate in the brain, but also relating that to hormones that we measure in the periphery to see if we’re seeing this relationship between peripheral hormone dysregulation and alterations in the hypothalamus, but also this neuroinflammation markers in combination with that. So that’s going to be trying to target her health hypothesis on this.
But generally, we’re just interested in making links between these three core areas. So, obviously, we have had studies that looked at cerebral blood flow, we’ve had studies that look at neuroinflammation, and we’ve had some studies that look at hormones and seeing alterations in all three.
What we’re really trying to do here is that we think all 3 may be linked. And so we wanted to see whether we see these cerebral blood flow issues related to neuroinflammation, if we see neuroinflammation related to altered alterations around the hypothalamus, and we see that’s related to dysregulated hormones. And so it’s really trying to connect all these three things up in this population group.
Dr. Meadows: That’s great! So in addition to some of the imaging techniques that you’re using in this study, I assume that also means then you’re doing blood analysis as well, doing blood draws. Are there other outcome measures that you’re incorporating in the study?
Dr. Armstrong: Yes, we are. So we do a number of surveys that will characterize patients by surveys, but also we’ll be taking blood. And part of this project, actually, what we have is the participants will come in, they actually come into the magnet, and we’ll be taking measurements of blood flow, and we’ll be measuring the metabolites around the hypothalamus in their brain, and then we’ll be asking them to do some hand grip strength exercises.
So just utilizing their hand to squeeze and create a little bit of a exertion component while they’re in the magnet. While that’s going on, we’ll be monitoring blood flow in the brain to see if we see a deficit. And after that, we’ll do some scans again on blood flow in the brain, but also again with looking for metabolites around the hypothalamus.
We’re taking a blood sample as well before and after this occurs, so that we can look at changes that have been precipitated by that slight exertion while they’re in the magnet itself. So that’s when we’re taking the blood measures and really fascinated to see those hormones that are different, but also some of these metabolic markers that we typically obviously do within our collaboration.
Dr. Meadows: Can you give a quick update on what stage the study is in right now?
Dr. Armstrong: So right now we’re waiting for ethics approval. We’ve gone through a number of iterations, and we’re pretty confident within the next month that’ll be approved. And so we’re really gearing up now just to start up recruitment aggressively for this, for this study itself.
So we’ll keep people posted, and we’ll surely have advertisements going out through Open Medicine Foundation and specifically through the StudyME registry. I think we’ll be targeting a number of people through that great registry that is held by OMF.
Dr. Meadows: That’s great. Well, we’re looking forward to the good news soon, hopefully.
Dr. Armstrong: Yeah, that’s right.
Dr. Meadows: So then I guess just to wrap things up today, I’ll just maybe give a short summary in my own words and you can check my facts here, make sure I’ve got it right. So really you’re kind of using a combination of blood draws and noninvasive PET and MRI scans to really kind of look at the connection between cerebral blood flow, neuroinflammation and hormones both at the hypothalamus and in the periphery. Does that sound right?
Dr. Armstrong: That’s about right, yeah.
Dr. Meadows: Okay, cool. So I’ll wrap things up there. And thank you so much for joining me today, Dr. Armstrong.
Dr. Armstrong: No problem. Thank you very much for having me.
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