[intro music]
Host – Dan Keller
Hello, and welcome to Episode Nine of Multiple Sclerosis Discovery, the podcast of the MS Discovery Forum. I’m your host, Dan Keller.
This week’s podcast features an interview with researcher Amit Bar-Or about how children with MS can illuminate early mechanisms of the disease. But to begin, here's a brief summary of some of the topics we’ve been covering on the MS Discovery Forum at msdiscovery.org.
According to a Cochrane meta-analysis, interferon-beta and glatiramer acetate are clinically similar treatments for multiple sclerosis. Researchers analyzed five head-to-head clinical trials and found that both drugs did similarly well in improving disability scores and MRI measures in patients with relapsing remitting MS. The researchers were not able to measure quality of life scores for the disease-modifying therapies.
We also published a Research Roundup this week all about social media and the role it plays in science. Social media can sometimes work against the scientific method if patients in a clinical trial are in the habit of oversharing on blogs, Facebook, or Twitter. Patients who discuss their symptoms online might affect the blinding of clinical trials. It’s not all bad, though. We also wrote about some great social media sites for researchers such as ResearchGate, LinkedIn, and even Reddit. We also shared some amusing links on how scientists can improve their communication skills such as the “Up-Goer Five,” a schematic of the Saturn V rocket explained using only the 1000 most commonly used words in English.
Every week we curate research articles on all topics related to multiple sclerosis and highlight our favorites in the “Editors' Pick.” Last week, some of our favorites were a review on oligodendrocytes, a research article about the origin and maturation of B cells, and a review about how the relationship between axons and myelin is involved in demyelination. You can see our weekly picks by going to our website, clicking on the “Papers” tab, and selecting “Editors’ Picks.” In addition to the Editors’ Picks, we link to every MS-related study found in PubMed. Last week was a banner week for MS studies. One hundred four were published, and we linked to them all.
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Now to the interview. Dr. Amit Bar-Or is an associate professor of neurology and neurosurgery at McGill University. Some of his work focuses on multiple sclerosis in children and how they can shed light on the origin of the disease.
Interviewer – Dan Keller
Welcome, Dr. Bar-Or. Let's talk about pediatric MS and what we can learn from it, especially about treating children but also about what it tells us about the disease, in general. Where does it stand now? What have you found in children?
Interviewee – Amit Bar-Or
Well the last few years have seen a substantial increase in the appreciation that MS can occur, does occur in children. Probably one out of every twenty adults with MS will have had an initial episode clinically that manifested in the pediatric age group, which one defines somewhat arbitrarily as 18 in most places. But the presence of MS in children, of course, you can imagine creates a particularly sensitive clinical context with a lot of challenges to both the child and the family and caregivers. So understanding more about pediatric onset MS – for the purpose of better caring for the children – is one important accomplishment of some of the more recent insights that have been gained in the groups that have been studied. The other, of course, is that a challenge that we have, in general, in the MS field is understanding more about what initiates MS. What are the initiating mechanisms? We've learned a fair bit but still have more to learn about the genetics and about the environmental contributions. And we know that in adults with MS one can measure certain abnormalities, for instance, in their immune response, but we really don’t know whether an abnormality that is measured in an adult represents a consequence of dysregulation and an epiphenomena that may be abnormal but is not going to benefit the illness if you treat it, as opposed to an abnormality that is very much involved in mediating the problem. So the children given that at least, on the average, they're going to be closer to the biological onset of the illness could this provide an opportunity to get insights into earlier mechanisms in a context that is less confounded by such epiphenomena of chronicity, of long-standing illness. And so, one is viewing the studies that are ongoing now – in terms of trying to better understand the pediatric MS context – both in terms of the merits of understanding them for their own sake, as well as a potential window into the broader spectrum. One of the first questions that you then need to ask if you're considering whether children can teach you about MS, in general, is whether MS in children is the same illness as MS in adults. Maybe they're different illnesses. And so one of the approaches that has been taken is to say in adults who develop MS as adults the field has identified certain genetic risk factors and certain environmental exposures that are thought to contribute to risk. And one of the first questions that has been asked is do those same risk factors – genetic and environmental – play out in children who develop MS? And the answer is essentially yes. For the same types of genetic contributors that have been identified in adults, one can see them as risk factors for developing MS in children. And the same environmental exposures – which include, for instance, low levels of vitamin D or exposure to a particular virus called Epstein-Barr virus at a certain phase – these again in children have emerged as being risk factors for the development of MS. So one thinks that at least based on that indirect evidence we can think of pediatric onset MS as, indeed, a reflection of the same illness at earlier time points and again reinforcing the value of understanding early mechanisms less encumbered by chronic disease processes.
MSDF
What early mechanisms have you been able to discern from looking at the development of MS in children?
Dr. Bar-Or
Well, there are a few very interesting observations that have emerged, and they include observations both on the immune system side and on the central nervous system side. So I'll start with the central nervous system side. We have always been challenged with the effort of trying to understand what are the actual targets of injury in multiple sclerosis. Certainly over the years, it's been described as an illness that affects myelin – the myelin making cells or the oligodendrocytes – so people have considered myelin antigens, or potential targets, as important targets in the disease. But much of that thinking has, in fact, been shaped by the most commonly used animal model system, which is experimental autoimmune encephalomyelitis, where you, in fact, inoculate the animal in its periphery with an antigen of the CNS typically a myelin antigen such as MBP or PLP or MOG. The animal has T cells that then get activated in the periphery that can respond to that antigen. They traffic to the central nervous system, identify the antigen, and contribute to an inflammatory injury process. In MS, though, we do not know what the triggering insult is or what they are in terms of the sequence, and we still don't really know what the actual targets of the illness are. This is important because more and more we've appreciated over the last decade or two that in addition to the myelin and the oligodendrocytes there's a very important injury to the neurons and their axons – the neuronal cell bodies and their extensions where they deliver their signals – which are typically wrapped in some cases in myelin, and others remain demyelinated or lacking in myelin. The issue of what the target is could guide both a better insight into initiating mechanisms – and how to deal with them therapeutically – as well as therapies that are designed to try to target very specific immune responses. Because if we knew what the specific antigens were, we might be able to develop approaches to change the immune system in what's called an antigen-specific way. Which means we try to change only the bad guys' cells or enhance the very specific regulatory cells that will control them without impacting the rest of the immune system, which would be conceptually much better in terms of having both benefit without risks of limiting the ability of the immune system to do, for the most part, what it does normally. One study in which we had the opportunity to compare spinal fluids from children presenting with a first episode of what may or may not be MS, and these children are then followed very, very carefully prospectively – meaning forward in time – as part of the Canadian Pediatric Demyelinating Disease Study was to establish over time who, in fact, has MS and who doesn't. And then go back to those early samples from that first clinical event and compare it what's called a proteomic level where we say we don’t know what the differences might be, but let's use a technology that breaks the CSF down – the cerebrospinal fluid down – into all of the components that make the different proteins. And then we have a survey of all of the different protein content and compare between the two. And we anticipated that we would see differences in those typical myelin antigens that the community has thought over the years are the relevant targets. So first surprise was we did not see any differences in those particular previously or traditionally implicated antigens. However, we did see differences in a number of molecules that are referable to a tiny little apparatus that serves an important physiologic function, and that's called the axoglial apparatus. That area is a tiny, tiny area where the glial cell – in this case the oligodendrocyte, the myelinating cell – its membrane dives down and attaches to the axon. That point of contact is part of what forms the axoglial apparatus. And it becomes a very enticing potential target of injury because an injury to that target would be expected to cause, on one hand, injury to the myelinating cell (maybe leading to demyelination) but also could produce an injury to the axon itself perhaps contributing to the axonal and neuronal injury. And again, we now know that both of those injuries are very much part of the MS disease process, or at least part of the consequence of the MS disease process. So this is just one study in children where we may be getting clues in a more refined way to the particular early targets of the disease or those structures involved in early in the disease, which is now guiding some of the thinking about how to followup on that both to better understand and potentially target therapeutically. An example on the immune system side is that there has been the sense in the broad community in MS and in other human autoimmune conditions that certain types of cells – that are called effector cells – may be dysregulated in MS either because they are overly active or insufficiently regulated or both. So either an effector problem, a regulator problem, or a combination of the two. But it's been difficult to identify which of these cell subsets is really involved in the disease as opposed to dysregulated, as I mentioned before, as a consequence of the disease. And the children have provided an opportunity to again look early on. And one study had identified that one of the abnormalities had appeared to involve a failure of normally developing regulatory T cells – this is work by Regitta Walderman (12:20) and Betina Belint at the time – which showed very nicely that in children with MS, as compared to controls, there seems to be a deficiency in the development or the maintenance of regulatory T cells. And in fact, it looked as though cells that normally get educated by an organ that we call the thymus, which is very active particularly in children, seemed to be getting older faster in the kids with MS. And so this raises the interesting question of whether there is a premature senescence or premature aging, in a sense, of certain immune cell populations so that over time their functional capacity is not quite the same, and if this is on the regulatory cell side and you have a diminished capacity for whatever reason you might expect the effector cells to be able to spillover inappropriately and participate in disease. So those are two examples – one of the neurobiological side and one of the immunological side – where children are providing what I would consider very important insights into the overall MS spectrum.
MSDF
Let me ask you about the injury to the axoglial complex. Glia provide supporting roles both nutritionally and through other molecules and as well as physically. Do you think this is an injury to the oligodendrocyte – which then impacts the axon – or is it some sort of attack which just hits this area, in general?
Dr. Bar-Or
Well this is a great question. And there's an ongoing discussion as to the chicken/egg; what gets injured first? What we do know is that when you look at the available tissue for studying pathology of MS – which, of course, tends to be quite biased to late in the disease where people may die for other reasons and postmortem – we have relatively little insight pathologically in what's happening in patients in early stages of the disease. Fortunately, people who develop MS even through the diagnosis rarely, rarely require a biopsy to get tissue to establish the diagnosis. And in fact, if you're doing a biopsy, it's usually because it's atypical, not typical. So we have several groups who are working hard and making important contributions, including into this earlier event, but there is still a big gap in our understanding of the early events and hence the very difficult to talk about initiating processes. But you bring up the very important context of the neurobiology of MS, which involves the ongoing function and integrity of the brain cells, including the neurons and the different glial cells. Those include the oligodendrocytes which make myelin but also the astrocytes which provide, among other things, important support to the blood-brain barrier and important support to the neurons, as well as the microglial cells which are very crafty cells of the central nervous system that probably performs several different functions. And all of these cells when they get activated or insulted they may fail to provide the normal physiologic protection, or they may even actively contribute to propagating injury. If you injure the oligodendrocyte in the myelin, the axon that is served by that myelin is working harder and may peter out over time. On the other hand, the integrity of the axon is important for the oligodendrocyte to maintain its myelination and its wrapping (15:34). So there's very important crosstalk, and it is very likely that injuring one element sufficiently will result in deterioration of the other regardless of which one you're injuring first. From a therapeutic standpoint, our efforts are to understand this crosstalk better and to understand how to try to establish protection, if not repair, of any one of these elements as part of the overview. It's clear that if you don't have an axon there's nothing to myelinate; if you don't have the myelinating cells you're left with bare axons that don't function or survival as well with the increased demand. And so, we need to have a more complete view so that we can approach not just a single biology at a time but, of course, we also – to understand any given biology – have to develop approaches that will isolate that biology so we can understand it. And one of our challenges is that we do not really have good models of those neurobiological aspects of MS to study. The EAE, for instance, which recapitulates some of the features of MS, has not really been shown to recapitulate those particular features that we're discussing.
MSDF
Finally, let me get back to one thing you mentioned that if you can identify the antigens of interest that are either spurring an attack or being targets of an attack the idea would be to find specific ways to approach those antigens. Now we have certain drugs that will deplete B cells, and they show benefit. We have certain drugs that will keep trafficking down cell adhesion molecules, and those seem to have benefit. Is there a focus on any particular antigens at this point and any particular approaches (clonal deletion, any sort of small molecules)? Where's that going?
Dr. Bar-Or
Well there are a number, and I probably won't be able to summarize all of them here. But there are generally several different strategies that try to target the immune system in a much more selective way than most of the approved therapies, including the not yet approved B-cell depleting approach which, of course, is more specific than targeting cells beyond B cells but is still depleting quite a few cells. Many of the B cells in the circulation, at least, are depleted. One extension to what you had raised is that it's fascinating to see how different approaches can achieve benefit of decreasing new disease activity, and we need to be able to sit back on a regular basis and integrate the insights from all of the successful, as well as unsuccessful, therapeutic interventions, including those that were not only unsuccessful in limiting new disease activity but the occasion where they increased new disease activity. What would appear initially paradoxical. Understanding all of that will give us very important insights into the disease itself. As far as antigen-specific approaches, one way is if you know what the antigen is – which, of course, we don't really know but we can hypothesize – you can try to develop induction of regulatory cells with that specificity or killing off or creating a state of unresponsiveness, also know as (18:40) of the effector specific cells or a combination of the two. There are different strategies that people have tried to use that are based, for instance, on the requirement of a T cell during activation to have an antigen-presenting cell present the antigen. And the profile of molecules both through contact and through secretion that the T cell can then receive in that environment of interaction with the antigen-presenting cell can often define the response profile, subsequently, of that cell. And if certain molecules such as costimulatory molecules are not present in that interaction or modulated, you might actually shut the cell down – you may not kill it, but it will be unresponsive or hyperresponsive – and that would be one strategy. Another, for instance, is to say well I don't know exactly which particular antigen, but I think it's myelin antigens. Let me get out of a patient's blood their immune cells and stimulate them to a variety of potential antigens, and whatever grows will reflect what grows in that person against the CNS antigens. And use that in a way to modify them so that they cannot cause problems and inject them back into a patient almost like a vaccine with a view that you are now giving that person whatever their T cells were that could respond to myelin, and their immune system now will respond to them and kill them and kill any other such cells that are present in the body leaving the rest of the immune system intact. And will that limit that person's ability to respond to their myelin? That again, is individualized medicine, which is one of the hot areas to pursue in the future, recognizing that if we hang our hat on a single target that may be true for one person but not for others or may be true for a person at some point in their illness but is not the predominant target later on. And so I think that using these kinds of approaches, which recognize the specificity or the selectivity, at least, as potential but also that there are very likely to be differences across individuals and maybe even with the same individual over time. And to try to individualize the therapy that is going to be most suitable for that person at that time.
MSDF
Thank you, Dr. Bar-Or.
[transition music]
Thank you for listening to Episode Nine of Multiple Sclerosis Discovery. This podcast was produced by the MS Discovery Forum, MSDF, the premier source of independent news and information on MS research. MSDF’s executive editor is Robert Finn. Msdiscovery.org is part of the non-profit Accelerated Cure Project for Multiple Sclerosis. Robert McBurney is our President and CEO, and Hollie Schmidt is vice president of scientific operations.
Msdiscovery.org aims to focus attention on what is known and not yet known about the causes of MS and related conditions, their pathological mechanisms, and potential ways to intervene. By communicating this information in a way that builds bridges among different disciplines, we hope to open new routes toward significant clinical advances.
We’re interested in your opinions. Please join the discussion on one of our online forums or send comments, criticisms, and suggestions to editor@msdiscovery.org.
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[intro music]
Host – Dan Keller
Hello, and welcome to Episode Eight of Multiple Sclerosis Discovery, the podcast of the MS Discovery Forum. I’m your host, Dan Keller.
This week’s podcast features an interview with researcher, Wendy Macklin, whose team studies myelination and demyelination in zebrafish and mouse animal models. But to begin, here is a brief summary of some of the topics we’ve been covering on the MS Discovery Forum at msdiscovery.org.
As listeners may already be aware, a new study suggested that infection with HIV is associated with a lower risk of developing MS. Researchers looked at a large sample of hospital records and found that individuals infected with HIV had a 62% lower risk of MS than HIV-negative individuals who were matched for age, gender, region, and socioeconomic status. The researchers think that antiretroviral drugs might be causing the protective effect, though it’s possible the infection with HIV itself somehow protects against developing MS. Antiretroviral drugs may attack some ancient viral genes thought to trigger MS and other autoimmune diseases.
Science journalist, Ricki Lewis, covered a study of patients with a rare mitochondrial eye disease that may be entwined with MS. The disease called Leber hereditary optic neuropathy, LHON, is a degenerative eye disease that causes progressive loss of vision. But in some patients, the disease can also cause MS-like symptoms. Researchers performed MRIs on patients with LHON and found that their white matter lesions resembled MS, possibly providing an early snapshot of MS. The similarity of the diseases has also led some researchers to question whether they share a pathogenesis, but the rarity of LHON and MS developing in the same person is shifting the opinion towards calling any comorbidity of the diseases just a coincidence.
In a recent post in MS Patient, Ph.D., blogger Griselda Zuccarino-Catania followed up her feature on DMTs in pregnancy with her own personal debate on whether to continue her DMT while breastfeeding. In her post, she profiles researcher Thomas Hale, who studies drug concentrations in breast milk. He’s found that concentrations in a woman’s blood plasma are associated with the concentrations in her breast milk. These levels can be used to assess the risk any drug might have to infants.
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Now for the interview. Science journalist, Carol Morton, met with Wendy Macklin at the Glia Meeting in Cold Spring Harbor, New York. She and Dr. Macklin discussed new research in myelination using the mTOR cell apoptosis pathway, the feasibility of a remyelinating drug, and her work with an unusual animal model for modeling MS – the zebrafish. [Note: the word "apoptosis" is incorrect and should not have appeared in the introduction to Dr. Macklin's interview. While it's impractical to remove it from the already-released audio podcast, we are correcting the error here, in this transcript.--Editor]
Interviewer – Carol Morton
There are not that many MS researchers who work with that.
Interviewee – Wendy Macklin
No, and there are times when you have to suggest that there is relevance to multiple sclerosis for looking at little two-inch fish. But they do. They provide really important information because you're not even looking at the two-inch fish; you're looking at the little, teeny tiny larva and embryos, but they are optically clear. So some of the new technologies use these green fluorescent proteins that originally were identified in jellyfish that make the jellyfish fluoresce at night. If you shine a certain wavelength of light, they turn green. And so, you can do that in a live animal, in a live fish; and in fact, some of the stuff that we were hearing today was even doing it in the mouse, but there you have to actually be able to get the microscope so you can actually see into the mouse brain. But in the fish, everything is transparent; so you can see it no matter what. So you just put the fish in a microscope environment, and you can watch cells, and you can take movies of cells moving, cells trying to make new processes, and cells wrapping around axons. And so you can watch this in realtime.
MSDF
You recently had a really interesting paper. Do you want to talk about...?
Dr. Macklin
So that paper came out of a project that we'd started a long time ago that was focused on understanding how one particular protein, Akt – which does many, many things in cells – regulates oligodendrocytes, which are the cells that make myelin. And it does many things; we thought it was involving in a survival element; and so we thought maybe we could find things that would help the oligodendrocytes survive immune attacks, survive things better and not die. And so we created a mouse where we overexpressed that protein in the oligodendrocyte. And instead, actually, what happened it did not change the survival of the cells at all; it changed how much myelin they made. And in fact, it drove the cells to make too much myelin. And in fact, if that becomes pathologic, the animals actually die when they're about a year old because they have too much myelin, and it's filling up their brain. So it's a dramatic change. And so, then we began to drill down to see well what is it about that molecule because it does many things? This particular hypermyelination syndrome was really feeding down through the mTOR pathway. And so, if you knockout parts of the mTOR pathway in the oligodendrocytes, the spinal cord is far worse and makes much less myelin and does not really generate the right kind of myelin. Whereas other parts of the brain are doing just fine or seem to be doing just fine. So one of the questions is why is this anymore damaged by this change in the cell? So the oligodendrocyte is identifying an axon and then wrapping around and making myelin, and that's what's the key question in MS is how to make sure that cell continues to make myelin. And we now have a system where we have changed the axons in some way – using again this mTOR pathway – and those axons don't encourage the oligodendrocyte to make myelin. So now we have a system where we can go in and try and figure out well what's fundamentally changed about those axons that they say don't myelinate me; whereas the oligodendrocytes in other parts of the nervous system are doing just fine making myelin.
MSDF
Now after the session this morning, I'm actually wondering if myelin making is now the goal, or has the goal…is the goal changing as people find out more for for therapeutic?
Dr. Macklin
I would say we don't know. So if you look in MS tissue, you see that where there's demyelination there still are oligodendrocyte progenitor cells, and there still are the cells that are trying to make myelin, the premyelinating cells. There's small numbers relative to the normal tissue, and they don't make myelin. So is that because we don't have enough cells? Is that because they have an inhibitor that's preventing them in that environment, or because they're not getting some positive signal? So I would still say the question of understanding how myelination is regulated has huge clinical relevance.
MSDF
Recently you went to another meeting that was really focused on myelination as a therapeutic problem, a therapeutic target.
Dr. Macklin
Right.
MSDF
In addition to knowing what's happening with the cells and the molecules in the environment in the brain, there's some other issues in getting myelin-making drugs through clinical testing.
Dr. Macklin
Yeah. In contrast to many of the other neurologic diseases, there are disease-modifying drugs out there for MS, but they almost all – at the current time – hit the immune component, which is absolutely essential and is definitely important. But even if you got rid of 100% of the immune component of MS, you still would have damage in the brain. And there is a good deal of evidence that the myelin not only does it allow better conduction of these axons, but it also provides all sorts of support. Metabolic it's providing energy to the axons; it provides a great many things to the axons that help the axons survive, which are part of the neurons. So if there is really still serious damage, you want to figure out some way to repair that. And so there are a couple of clinical trials actually going on right now that are looking at drugs that might enhance the remyelination in patients. And so, some of the things that we're doing – looking both in the fish as well as in the mouse – are pathways that could be targeted for therapeutics that might help you to enhance myelination. One of the big themes that came out of that meeting last month was that if you had the perfect therapy for remyelination – you know that it works well in the zebrafish; you know it works well in the mouse – you can get other models that allow you to look at remyelination in a number of different contexts. You have to get those to patients and see if they actually do create new myelin. In patients, the problem is that the current imaging modalities for patients, MRI, is measuring water. And where you have myelin there is less water because of the way myelin works. It's hard to know exactly why there's less water where you're looking in MRI. So there's a variety of different approaches. There's new techniques with MRI. There's even some new PET techniques – which are clearly experimental at this stage – to try to really be able to show new myelin. And part of that meeting was really if we had the perfect therapy how would we prove it in a clinical trial? You can show clinical improvement, which is great, but is that because of you've changed the immune system, because you've changed other aspects of the patient, or you really have new myelin? That's currently still a really hard problem in terms of the the clinical end of things to really be able to prove that. Nevertheless, people are developing these kinds of drugs, and as I said a couple of them are in clinical trial right now.
MSDF
Looking at your animal models, the ways that you have evaluating more or less myelin are ways are ways that can't be translated to people…
Dr. Macklin
Well some of them are. I mean that's really where some of this work is going is trying to figure out how to use either MRI or PET imaging of live animals, and then you can go and test. And you think you have a signal that tells you you have increased myelin then you can actually go in and check and see – at the tissue level – is there really new myelin? So you can validate some of these imaging modalities that way. But you you will always have to go eventually to the patients and be able to really demonstrate that that particular way of imaging the tissue proved in in an animal model really does mean something in the patient as well.
MSDF
I've seen those little mouse MRIs.
Dr. Macklin
They're so adorable.
MSDF
They are.
Dr. Macklin
And they definitely show you something. They definitely show you something. And some of the PET work…the PET work is more specifically directed to myelin so you can have a PET ligand, which shows up in PET imaging, that just literally binds only to myelin or binds predominantly to myelin, and it will go into the tissue, and it will bind there. And that actually gives you some fairly discrete imaging that because you know it's a molecule that only binds to myelin when you see that signal in a particular place you know that that is myelin. And if you see more of a signal, then you know that that's more myelin. So those are really interesting approaches, and they're very much more directed to being able to specifically say that's myelin that you're seeing. But in the clinical context, those kinds of approaches are being worked on, but they're still very early stages. In terms of trying to set up a clinical trial, those kinds of approaches may be the way you'll go eventually, but today you couldn't do it that way.
MSDF
Anything else that I should be asking, or that you wanted to add that would in in this context that would be interesting?
Dr. Macklin
Well I mean I think at this stage there are other issues of the question of so much of the work is done on myelination, which is crucial during development, and it's absolutely essential. And problems with normal myelination during development result in really serious brain problems. There are ways to study developmental myelination: in the fish, in the mouse, in a variety of different ways. And then there's a series of adult ways of getting rid of myelin to look at remyelination. And so, the overwhelming perspective has always been well whatever you learn from the myelination during development would be exactly what you would need to know about for the remyelination in the adult. And much of that's true. I mean you have to get the cells, you have to get the cells to proliferate, you have to get them to the right place. But there are now data that suggest that there are definite differences in the way the adult cells are responding to their overall environment, which is totally different than from the developmental environment. The cells may be very similar, but in the developing environment the many things are changing all of the time – the nerve cells, all of the different cells are changing, the brain is getting bigger – there's all sorts of changes. And in a damaged adult brain, you see certain differences that do seem to be real in terms of the way the signaling pathways are that would regulate how the myelin is generated in the remyelinating context versus in the developmental context. So we do need to go back and forth even the ones of us who work on the fish. We need to be able to look and see some adult context that's a demyelination/remyelination context that those same things that you're seeing developmentally are important in the adult.
MSDF
That is interesting because I have heard people say well you recapitulate, you want to recapitulate the…
Dr. Macklin
Yes, and it does. It…
MSDF
…the developmental pattern.
Dr. Macklin
Right.
MSDF
So that's interesting in that. Okay, well that's fabulous. Well, thank you for taking the time to do this.
Dr. Macklin
Okay. Certainly.
MSDF
It was wonderful.
Dr. Macklin
I hope it's useful for you.
MSDF
Okay, great.
[transition music]
Thank you for listening to Episode Eight of Multiple Sclerosis Discovery. This podcast was produced by the MS Discovery Forum, MSDF, the premier source of independent news and information on MS research. MSDF’s executive editor is Robert Finn. Msdiscovery.org is part of the non-profit Accelerated Cure Project for Multiple Sclerosis. Robert McBurney is our President and CEO, and Hollie Schmidt is vice president of scientific operations.
Msdiscovery.org aims to focus attention on what is known and not yet known about the causes of MS and related conditions, their pathological mechanisms, and potential ways to intervene. By communicating this information in a way that builds bridges among different disciplines, we hope to open new routes toward significant clinical advances.
We’re interested in your opinions. Please join the discussion on one of our online forums or send comments, criticisms, and suggestions to editor@msdiscovery.org.
[outro music]
[intro music]
Host – Dan Keller
Hello, and welcome to Episode Seven of Multiple Sclerosis Discovery, the podcast of the MS Discovery Forum. I’m your host, Dan Keller.
This week’s podcast features an interview with neurologist, Dr. Daniel Kantor. But to begin, here's a brief summary of some of the topics we’ve been covering on the MS Discovery Forum at msdiscovery.org.
At MSDF, we publish short, medium, and long articles. The longest News Synthesis articles cover an entire area of MS research. In one recent News Synthesis, science journalist Cynthia McKelvey, provided a primer on epigenetics. Epigenetic modifications are defined as any change to gene expression that happens without altering the
DNA sequence, and they could be the key to understanding heterogeneity in MS. Though the literature on the role of epigenetics in MS is growing, the field remains in its infancy and is not very well understood by many MS researchers and clinicians.
The medium-length articles we call New Findings, and they focus on either a single study or a small group of closely related studies along with comments from experts not directly involved in the studies. An excellent example by Science journalist, Mitch Leslie, explores an iPad app that may become a more convenient alternative to the much maligned Expanded Disability Status Scale, the EDSS. The app mimics four tests in the Multiple Sclerosis Functional Composite test. In an initial study, the app was sensitive enough to discern people with MS from healthy controls. If future trials are successful, it could allow patients to test themselves at home. It could also streamline data collection making the app useful to researchers as well. Our article includes a video demonstrating the app in action.
Then there are the News Briefs—short, meaty, and easy to digest summaries of noteworthy studies. For example, we reported on a large international survey that recorded a high statistical correlation between physical activity and health-related quality of life in MS patients. Another news brief looked at a study showing that evaluating a patient’s treatment preferences may play a key role in how long he or she will stick with a disease modifying treatment. We also reported on a study that described differences in overall brain atrophy between MS patients with oligoclonal bands and those lacking them.
Now for the interview. Dr. Daniel Kantor is a neurologist based at the Neurologique Foundation in Florida who is concerned with MS patients’ access to care. Dr. Kantor met with MSDF editor, Bob Finn, to discuss this issue.
Interviewer – Bob Finn
Dr. Kantor, welcome
Interviewee – Daniel Kantor
Thank you.
MSDF
In a recent article in MS Focus, you wrote that there are three types of access to care. What are they?
Dr. Kantor
Access to care means many things. Sometimes people think access to care just means access to medications. But access to care actually means access to physicians, access to medications, and then access to all the other diagnostics and other types of testing.
MSDF
And how would you grade the US healthcare system on each of those as it relates to MS patients on each of those factors?
Dr. Kantor
2014 has been an important year with the Affordable Care Act as well as with other federal legislation as well as state legislation that's happened. Access to care for some patients has gotten better. People who maybe couldn't get insurance have been able to get it. For a lot of people, though, their access to care has either remained the same or actually their access has come down. What I mean by that is somebody who could see the physician of their choice in the past now, in 2014, has found it increasingly difficult to have access to physicians who are familiar with their care, familiar with their disease state, and familiar with the treatments that are out there.
MSDF
You mentioned the Affordable Care Act. How is that specifically affecting access to treatments, access to physicians, access to diagnostics?
Dr. Kantor
The Affordable Care Act did several things. One of the things that happened in the Affordable Care Act was the creation of these exchanges or the marketplace. So in states that either ran their own marketplace or that go with the federal marketplace, there are plans that are really "stripped down" insurance plans. And that means that there's more restricted networks – meaning the patient has less choice when it comes to who to see about their disease state – and there's also sometimes more restrictive choices in terms of the medications. So you have less physicians to offer them care, maybe not physicians who specialize in multiple sclerosis, and then that physician also has less choices of what to use. So as you can imagine, those things get compounded, and a patient may have a lot less access to care than they would have had otherwise. A simple example is a patient who did not have insurance and now has insurance. So a patient who didn't have insurance before they've gained access because now they carry a plastic insurance card. But while they may have been paying a reasonable sum to a physician to see them with a cash pay, now that physician is not offered on their health insurance plan. While they may have been part of a patient assistance program with many of the pharmaceutical manufacturers, they may or may not still be eligible for those same patient assistance programs. Meaning that a drug that may have been free to them – or very low priced – may be even more expensive to them now.
MSDF
At MSDF, we recently ran an article about a study; it was a survey of neurologists. And the survey was looking at a number of different things. But the neurologists were saying that their patients were happy with fingolimod but not happy with their insurance companies giving them access to fingolimod. What other sorts of issues like that are arising in MS?
Dr. Kantor
I think it's a perfect example. Prior to 1993, we had no disease-modifying therapies that were FDA approved. Since 1993, we now have 10 separate branded products. That's an amazing leap forward. Not many fields in medicine have seen that kind of increase and certainly not in the world of neurology. For many patients with other neurological conditions – like Huntington’s disease, amyotrophic lateral sclerosis or Lou Gehrig’s disease, even stroke – they look at MS, and they're jealous. They have seen such an increase in the amount of research. At the same time, however, we see a decrease in the practice. We see it being harder and harder to actually practice good MS clinical care. And so, while patients may have access in some ways to medications that have even more efficacy than our traditional medications, if a patient can't get their medication or has to go through many, many insurance hoops to get there, then that's not good for them.
MSDF
What's the solution?
Dr. Kantor
The solution really is the neurology, physician, nurse practitioner, and physician assistant and community working alongside the patient community together and engaging our colleagues in the managed care world. Like it or not, in America, healthcare is usually paid by somebody else. Most people do not walk into a hospital or walk into a doctor's office and write the payment themselves. They are either part of an employer group – where the employer is frankly handling much of the payment – or now they're part of exchanges, or they may even be part of a federal program like Medicare or a state program like Medicaid. So the client for the doctor is not really the patient. Our patients are our patient; and we have a Hippocratic Oath; and we have a long, long time of tradition of what we do for that physician/patient relationship. But it's not really a client relationship. That might be good/that might be bad, but it's the fact. In fact, for most practicing physicians, most practicing clinicians, our client is actually the insurance company. And so that means that there's some disconnect between what a patient might think they want and even what the physician might think they want for the patient and what the patient actually gets. So what we need to do, though, is engage these managed care organizations better in terms of recognizing that things like step edits, like prior authorizations those are here to stay. Sometimes some neurologists see them as so unethical that the real prior authorization should be the doctor's prescription. The fact is that that's not the case. And it's going to be very hard to change that system (9:26) unless the person who's actually paying is the actual patient. And so recognizing that managed care organizations are there to manage their medical costs we need to work better at giving them the tools they need. We think that there's no guidelines for treatment of MS; there actually are; there are many guidelines. Each state – if you look at the major insurance company in that state – their prior authorization and utilization management criteria that is the most commonly used guideline for multiple sclerosis in that state. So while we may think, as physicians, it doesn't exist, it does exist; it's just not being written by us. These are being written by pharmacists at either pharmacy benefit management companies or pharmacists at insurance companies, and they're deciding the fate of our patients. We need to take a more proactive stance and work together at developing guidelines that can make sense and that have also "outs". What I mean by that is even if you say that we have a treatment algorithm that works for most patients there's always going to be patients who for some reason or other you don't want to put them through that algorithm. An example may be if you're going to start a medicine that has a potentially high chance for a certain side effect – and you think from past experience that that patient may have that side effect because they've been on similar medications with a similar side effect – then you may not want to put them through that algorithm. You may want to say well they haven't failed the medicine yet, they haven't had an intolerable side effect from this medicine, but they've had from a similar medication. And that becomes a big issue, for example, in the use of one of the oral medication, dimethyl fumarate – also called BG-12 or by the brand name of Tecfidera – where we do see significant GI side effects. For a lot of people, we don't; for most people they tolerate it well. But if you have a patient who has already shown you on multiple other medications for different symptoms that they have sensitive stomach, then even without a diagnosis of Crohn’s disease or celiac, you still would probably want to avoid using that medication. So that's an example where it's not a contraindication listed on the label, it's not an absolute contraindication – and it may not even be considered a relative contraindication – but in the physicians' opinion that patient would have a negative outcome because of that medication that's where they shouldn't go through that algorithm in the same way.
MSDF
How successful are you at convincing insurance companies of that?
Dr. Kantor
I think we're getting increasingly successful. In 2009, we started a group which was at first called the SouthEastern MS Consortium, or seMSc, sort of like the SEC in football. And then Texas A&M entered the SEC in football so we expanded to the Southern MS Consortium. And we go from Texas east and Delaware south; we take the most liberal definition of the South. Now there are members from California, Minnesota, Pennsylvania, and we're actually about to relaunch and rebrand as the Medical Partnership for MS. And the idea was that prior to this MS neurologists, as well as nurse practitioners, physician assistants, speech therapists, physical and occupational therapists, case managers, social works didn't feel like they had a voice when it came to advocacy for their patients. They felt like the existing organizations didn't always reflect what they're going through and what their patients are going through with taking a proactive stance on some difficult issues but by engaging in a collegial way with the insurance companies. Instead of taking in a stance that every medication should be available for every single patient, we've taken a more reasoned approach of while that may be in an ideal world that's not the world we live in. And so, let's look at the different utilization criteria, utilization management criteria, of the different insurance companies and work with them on a one-by-one basis. So we have constant conversations with insurers throughout this country.
MSDF
Dr. Kantor, I thank you very much.
Dr. Kantor
Thank you for having me.
[transition music]
Thank you for listening to Episode Seven of Multiple Sclerosis Discovery. This podcast was produced by the MS Discovery Forum, MSDF, the premier source of independent news and information on MS research. MSDF’s executive editor is Robert Finn. Msdiscovery.org is part of the non-profit Accelerated Cure Project for Multiple Sclerosis. Robert McBurney is our President and CEO, and Hollie Schmidt is vice president of scientific operations.
Msdiscovery.org aims to focus attention on what is known and not yet known about the causes of MS and related conditions, their pathological mechanisms, and potential ways to intervene. By communicating this information in a way that builds bridges among different disciplines, we hope to open new routes toward significant clinical advances.
We’re interested in your opinions. Please join the discussion on one of our online forums or send comments, criticisms, and suggestions to editor@msdiscovery.org.
[outro music]
[intro music]
Host – Dan Keller
Hello, and welcome to Episode Six of Multiple Sclerosis Discovery, the Podcast of the MS Discovery Forum. I’m your host, Dan Keller.
This week’s Podcast features an interview with Dr. Jeffrey Dunn, who explores the prospect of personalized medicine in MS. But to begin, here’s a brief summary of some of the topics we’ve been covering on the MS Discovery Forum at msdiscovery.org.
Recently, blogger Emily Willingham shared a person experience with MRI interpretation in our blog, MS Patient, Ph.D. She wrote, “I’ve come to realize in my various dealings with MRI reports that neuroradiologists are like economists; everyone has an opinion and no two readers will agree on what they see in exactly the same data.” Willingham, a developmental biologist, provides a unique view into the life of an MS patient. Her experiences bring a first-person perspective of MS, while her scientific background informs her insights in a way that many researchers and clinicians may find valuable.
We’d also like to bring your attention to the data visualization section of the MSDF website. Under the research resources tab, you can find a series of interactive data visualizations useful for MS researchers. One visualization aggregates 106 clinical trials. You can organize the data by the compound, phase, population, or even the funding. Our latest visualization is of the natural history of MS symptoms. The interactive bar chart allows you to see the change of various symptom severity in MS over a 30-year period.
Also in research resources, check out the drug development pipeline. This is where we keep detailed information on, at last count, 40 drugs currently in development or on the market for MS. This database, which is updated daily as new information becomes available, contains a wealth of data on each agent. This includes the agent’s class, its intended target and routes of administration, its regulatory status and commercial history, its chemical properties, mechanism of action and adverse effects, and all its clinical trials.
Now for the interview. Dr. Jeffrey Dunn is a Professor of Neurology and Neurological Sciences at Stanford University. He met with MSDF editor Bob Finn to discuss the use of biomarkers and personalized medicine. But first he shared a little history.
Interviewee – Jeffrey Dunn
So, in the history of multiple sclerosis, when cases of CNS demyelinating disease were first discovered, they were discovered as isolated case instances at a number of different and variable institutions throughout Europe and in the United States. The doctors knew of the patients’ symptoms, of course, because they had cared for them. Many of these patients went on to pathology examination, and multiple cases of areas of inflammation or even scar formation were seen within the central nervous system. These cases from the mid-1800s and into the late-1800s were described as isolated instances. And the physician who is given credit for the discovery of what we now know to be multiple sclerosis was Dr. John-Martin Charcot in Paris, because he had had the experience of a very close relationship with a patient he named Mademoiselle V. He had known that she had had a tremor and ataxia and eye movement abnormalities, so Charcot knew his patient’s phenotype, her clinical manifestations, very well, and specifically had seen evidence of eye movement abnormalities, tremor, and ataxia. She had consented to have her nervous system evaluated pathologically, and so Charcot was able to make a connection between what she had looked like in life, and then what her brain and spinal cord had looked like after she had passed away.
It’s that clinicopathologic correlation that really was a paradigm-buster at the time. And Charcot found palpably hard spots – areas of gliosis or scar formation – that occurred in plaques and patches throughout the spinal cord and brain (and cerebellum in this case). He called the disease almost an adjective really; he called it “la sclérose en plaques”, which is French for sclerosis – meaning hard spots essentially – in plaques. So hard spots was the disease. Multiple sclerosis is really an adjective more than a diagnosis. But in the early 20th Century leading up to the mid-20th century, there was increasing recognition on the basis of these isolated case reports that this disease that was now increasingly being called multiple sclerosis might be far more common than people had realized, and great credit needs to be given to Sylvia Lawry, who as you know was the founder of the National Multiple Sclerosis Society. The National MS Society was put together to try to bring physicians together to create a forum by which they could crosstalk, share the anecdotal information each of them had compiled, and come up with a more systematic review so that the disease could be better described and so that treatments could be more likely discovered. This was a huge step forward in terms of our discovery and ability to diagnosis and ultimately later to treat MS, but it created a framework that said that MS was, in some respects, one disease.
Now all of us even today, I would say, as physicians are trained that MS is a distinct disease; that it’s one type of disease with many variations according to individuals, but I think we’re actually at the very beginning of a very important paradigm shift in this consideration. There’s a difference, of course, between a disease and a syndrome. A disease is a quantifiable isolated entity – a classic example might be a genetic disorder caused by a single mutation in a coding sequence of DNA – whereas a syndrome is probably a collection of different but closely related diseases. I think there’s increasing evidence now, an increasing recognition that MS may be very heterogeneous and variable across individuals; I don’t think there would be any argument among my colleagues that MS is a heterogeneous process. My suggestion to you is that now, I think, we’re at the threshold of a paradigm that says that MS should not be regarded as a monolith or a single pathologic entity, but maybe more as a Stonehenge; a collection of closely related conditions that share some common pathology, but that need to be considered on an individual basis.
At the clinical, radiologic, immunologic, and pathologic levels we have evidence that MS is very heterogeneous among individuals. I think the theory that we now need to proceed according to is that multiple sclerosis is not one disease entity, but a number of different conditions. This idea and paradigm of personalized medicine is gaining traction. Our oncology colleagues who treat cancer have used this with some great and promising success in terms of applying optimum regimens and chemotherapeutic protocols to their patients, but I think there’s tremendous opportunity in multiple sclerosis to practice personalized medicine, because I think that the process of MS is a personalized one in which there are unique and eminently measurable proteins or protein profiles one day we’ll be able to identify, and hopefully that day is soon, and we can use that as the rationale for our prescription for the patients.
Interviewer – Bob Finn
So when some people think about biomarkers, they think about an individual protein or some other biological signal that will be prognostic or in some other way tell you about what the patient is experiencing or might experience. It sounds to me like you’re talking about not an individual biomarker, but a constellation of biomarkers that would provide a fingerprint. Am I right about that?
Dr. Dunn
I think so. Just as the disease pathogenesis itself is heterogeneous, I don’t think that one single protein would be able to help us. What I would foresee as an individual approaches us, that we might do a panel. There’s a series of questions that has to be asked. The immune process itself is sequential and acts, I think, as a cascade, and we have some biomarkers today that are available. I think you could argue them as biomarkers that help us in decision-making, that help the clinician decide what might be the best therapy, at least in terms of risk-benefit balance, but we just don’t have enough of them to be able to make the kinds of personalized decisions that I think we all hope we’ll be able to make one day.
MSDF
Would you mention a couple of the ones that are – or some of the ones – that are available now?
Dr. Dunn
So one example that I think would be well agreed on is the presence or absence of JC virus infection that can now be measured by a two-step ELISA assay, with a false-positive rate of an estimated 2.5%. One of the great challenges we face in treating MS is that we have to, in some respects, down-regulate the immune system to protect the brain and central nervous system, but we can’t overshoot the mark to cause a systemic immunosuppression. Immunosuppression can manifest in a number of different ways, including opportunistic infections and even malignancy. One of the most lethal and daunting of the opportunistic infections is a condition called progressive multifocal leukoencephalopathy – that’s precisely why we tend to call that PML instead, three syllables is far preferable – and that condition is caused by an infection of an otherwise relatively benign virus called JC virus, that if it gets into the central nervous system and begins to affect oligodendrocytes and cells of the central nervous system, can cause rapid intracellular proliferation and damage to the brain; that can spread geometrically throughout the brain and can cause very profound brain damage, and sometimes cases of death as well.
We’ve known of PML previously in patients with lymphoma and also in patients with untreated HIV infection who had severe and advancing immunosuppression. But we’ve seen this same PML condition in immunocompetent patients who have been treated with some of the agents that we might use for multiple sclerosis. This concern is not unique to MS, but it’s a concern with any immunotherapy that you use. The ability to measure whether a patient has previously been infected with a JC virus or not helps us in the risk-benefit balance considerations we have to make on behalf of our patients. It’s known that the absence of evidence of a JC virus infection is associated with a markedly decreased risk of PML, whereas its presence means that’s an active consideration in our prescribing.
Now that, I think, functions as a biomarker. Any time you might see an elevation of a measurable protein or another biomarker in general that normalizes with remission that gives you the opportunity to suggest that that either might be a therapeutic target – so let’s just call it protein X, for example, just for simplification and clarification. If a patient having an MS attack has a measurable increase in protein X in their blood which then now returns to normal or what had been their previous baseline in remission, that tells the clinician investigator that protein X might either be part of the immunologic cascade that causes the MS attack, and therefore suggests that the ability to intervene, down-regulate, or modify the expression of protein X may help with disease pathogenesis, OR it could also mean, or it could emerge as a candidate as a tool of assessment for disease status, so that one question we always have to ask as clinicians when we start patient on any given therapy or just in following them is how are they doing. Of course, that’s a primary mandate for the clinician taking care of patients.
Today, we do that by asking how they’re feeling, we strive to get into quality of life metrics with them, we also turn to their examination findings to look for interval change, and we look at MRI to see if there’s been a change there, with the hope that we’re seeing no evidence of disease activity. But the field of multiple sclerosis does not have its own version of a hemoglobin A1c, such as our endocrinologists have. In that scenario for those that aren’t familiar with it, A1c can be a value obtained literally with a single drop of blood that tells the practicing clinician caring for the patient what the average blood sugar of that patient has been over a substantial period of time prior to the time of their clinical encounter. So it helps the clinician make wise judgments and counsel to the patient regarding the optimum way to treat their diabetes, whether adjustments have to be made in their diet or in their prescription medications.
We don’t have such a thing in multiple sclerosis today. If we could find such a thing, it would make our care, I think, far superior in its quality. I think it would make physicians’ advice to our patients far more wise, and it would make the entire medical enterprise of caring for the MS patient less expensive, because we wouldn’t have to resort to important but still somewhat stodgy and expensive technologies like serial MRIs done with what could be high-frequency for the patient. Serial MRIs are safe for the patient, but you can see that if we could identify such a biomarker as that, if that were possible, I think that would have revolutionary implications for our care of the MS patient, not just in reducing medical costs – that’s an important goal – but the more important goal and what physicians need to focus on is superior advice, improved advice and counsel to the patients that are in our care.
MSDF
So you and I are both old enough to remember when the Human Genome Project was proposed, and one of the values of the Human Genome Project that was articulated was that it would usher in an era of personalized medicine. Now it’s 13 years or so after the Human Genome Project has been completed, and, arguably, that promise has never been realized. How much longer will it take in multiple sclerosis to realize an era of personalized medicine?
Dr. Dunn
The short answer is I don’t know, but there’s some important considerations to be made along the way. One fact is there are approximately 25,000 genes in the human body, but there are an estimated 500,000 proteins. The reason for the difference is that after an original protein is manufactured on the basis of the blueprint of DNA, it can be modified in transcription and translation. For those of you in your field, this would be post-production modifications. The same thing happens with proteins, and what that means is that the field of proteomics, you could argue, is 20 times more sensitive than the field of genomics if the ratio is 25,000 to 500,000 genes to proteins in the human body, respectively.
MS does have a genetic component, and that’s been proven by research in this past two decades by our country’s leading researchers, but the genetic input of MS is not the only answer; MS is only partially a genetic disease. It seems to be, in my own opinion and I think it’s shared by my colleagues – many of them, most of them perhaps – is that MS is primarily an environmental condition. The greatest risk of obtaining MS is not so much that family members are affected, though cases of that have happened and happen regularly, it seems to be more related to environment, where one lives. Now you may know that epidemiologically, MS is almost absent, or very sparse, at the equator, but in moving north and south on Earth, the greater that one moves away from the equator, the greater the prevalence of MS. And right about the 35th parallel or so both north and south of the equator, there appears to be a relatively large increase in how much MS there is. And that’s true, to the best of our knowledge, all the way around the world.
And so if MS is more of an environmental condition than a genetic one – although it’s both – then I think a genetic assay may be part, but not likely to be all of the answer, and the promise of going to a more sensitive assay to get into the post-transcription and post-translational modification that takes place in human molecules, which ultimately are the language of how the immune system affects our nervous system, is going to be and prove to be a more enriched and more promising field of inquiry.
MSDF
I wonder if you can mention some of the labs that are doing the most promising work in this area.
Dr. Dunn
I’m pleased to say that there are labs throughout the world that I think are doing research in this. Within the United States – I don’t want to leave anybody out – but I think that special kudos need to be given to the Mayo Clinic. I think on the east coast the Partners Program of the Harvard Medical Schools are very interested in this field; Johns Hopkins is doing work that I think is exemplary. Out west, our colleagues at UCSF. And, of course, I have to give special kudos to my colleagues at Stanford University. These are places that are publishing in translational medicine the bench-to-bedside framework in which discoveries that are being made at the level of the bench, there’s an active effort being made to try to translate that to human care. I’m very sensitive to the idea of excluding anybody, because I think that this is really an international search, and it’s going to require multilevel of collaboration. So I hope that as we go forward, we’ll be able to really work together.
I mentioned just a moment ago, I think practice of personalized medicine in this field is going to require not one discovery, it’s going to require a panel, perhaps, of different measurable biomarkers. I don’t anticipate one single lab is going to be able to discover all of those biomarkers, I think we’ll get one discovery from one place, one from another, one from another. And it’s going to require a transcendent collaboration between institutions and individuals and researchers and investigators to bring it all together for the collective good.
MSDF
Dr. Dunn, thank you very much.
Dr. Dunn
Okay, alright, thank you very much, Bob.
[transition music]
Thank you for listening to Episode Six of Multiple Sclerosis Discovery. This Podcast was produced by the MS Discovery Forum, MSDF, the premier source of independent news and information on MS research. MSDF’s executive editor is Robert Finn. Msdiscovery.org is part of the nonprofit Accelerated Cure Project for Multiple Sclerosis. Robert McBurney is our President and CEO, and Hollie Schmidt is Vice President of Scientific Operations.
Msdiscovery.org aims to focus attention on what is known and not yet known about the causes of MS and related conditions, their pathological mechanisms, and potential ways to intervene. By communicating this information in a way that builds bridges among different disciplines, we hope to open new routes toward significant clinical advances.
We’re interested in your opinions. Please join the discussion on one of our online forums or send comments, criticisms, and suggestions to editor@msdiscovery.org.
[outro music]