November 28, 2017

NIH ME/CFS Advocacy Call - November 2017



Moderator: Margo Warren
November 28, 2017
1:00pm ET

Coordinator: Thank you for standing by. I’d like to inform all participants that your lines are on listen-only until the question and answer session of today’s call. At any time if you’d like to ask a question, please press * followed by 1. You’ll be asked to record your name. Please state your first and last name so I may introduce you prior to asking your question.

Today’s call is being recorded. If anyone has objections, you may disconnect at this time.

I’d now like to turn the call over to Ms. Margo Warren. Thank you. You may begin.

Margo Warren: Hello. My name is Margo Warren. I’m the Acting Director of Communications and Public Liaison at the National Institute of Neurological Disorders and Stroke. On behalf of NIH I’d like to welcome you to today’s telebriefing and thank you so much for your interest in participating in this discussion with us today.

Our Director Dr. Walter Koroshetz will introduce the speakers, each of whom will make some remarks. After which we’ll open the phone for your questions. The speakers will try to keep their remarks brief so that we can answer as many questions as possible in the time remaining on the call. Dr. Koroshetz.

Walter Koroshetz: Hello and welcome everyone. This is our third telebriefing of 2017. And we very much look forward to sharing with the ME/CFS community the research that we are doing here at NIH and funding in the universities and clinics around the country.

We are concentrating primarily on giving you new information that has occurred since the last telebriefing. So this is just a slice of the ME/CFS program, but an important update.

The first speaker this afternoon will be Dr. Avi Nath, who is my colleague here and the Director of the clinical program at the National Institute of Neurological Disorders and Stroke. And I, as the Chair of the Trans-NIH committee that includes many institutes interested in trying to help solve this problem, are also involved in the intramural research program, which you’ll hear an update about from Avi.

After that, Dr. Breen will give an update on the new collaborative research center project that we are in the midst of launching now. And also Vicky Whittemore will talk about the Common Data Elements project in ME/CFS and how that’s coming along.

As mentioned, we are launching now a collaborative research program to try and better understand ME/CFS, what causes it and what treatments might be helpful for folks. And we’re very happy to be joined by Dr. Derya Unutmaz from the Jackson Labs in Connecticut and he’s the principal investigator on one of the centers in the collaborative research centers project. He’ll provide a brief overview of his plans.

The topic of his center is called “Topological Mapping of Immune, Metabolomic and Clinical Phenotypes to Reveal ME/CFS Disease Mechanisms.” Dr. Unutmaz and his group will use novel tools to take a detailed look at how the immune system; the microbiome, which is our body’s complete collection of microbes, including bacteria and viruses; and metabolism, which are the chemical reactions to produce energy for our body, how these all interact in ME/CFS is the topic of his center.

As you know, since the last telebriefing in July we have awarded three center grants. And these will be researched as coordinated through one Data Management and Coordinating Center. And we hope that this will form a strong foundation for ME/CFS research in the US. And I want to emphasize that this is a beginning. This is a seeding project to bring ME/CFS research to a new level.

And we think that this is the most effective way of doing it, is to start out with a number of very highly motivated, high-level research institutions to come together and work together to try and address this problem. We think that this will bring in a much greater and wider group of researchers into the ME/CFS field. So, we’re very much looking forward to the progress there.

As always, we do this telebriefing to learn from the community. And so we’ll keep our remarks brief and open the line for questions.

So that’s the brief intro. And with that, I’d like to turn it over to Dr. Nath to give a quick update on how things are going with the intramural program. Avi?

Avi Nath: Yes. Thank you, Dr. Koroshetz. Let me just start by saying that, for one, I’m very, very grateful to all of the patients who have participated in our study and expressed willingness to do so. And I’m happy to report that you know, we’ve been very busy and we’ve been recruiting really well. So we’ve had hundreds of inquiries from there. We’ve so far brought in 26 individuals, 11 patients and 15 controls.

And as you know, it’s a very extensive study. So everyone is here for a week and they’re extremely busy during the time that they’re here. But everything’s gone very, very smoothly.

Out of the 15, out of the 11, sorry, 11 patients we’ve now adjudicated five. Four met our eligibility criteria of which two are coming back. The other two, one got pregnant and one decided to go back to school. And then the other six are being adjudicated. So they will come for second visits.

But, we still continue to recruit. And so we have somebody in-house all the time now on a regular basis.

So that’s where we stand at the moment.

Walter Koroshetz: Okay. Thanks so much, Avi. And so Joe, do you want to talk a little bit about the Collaborative Research Center Program?

Joe Breen: Sure. Thank you, Dr. Koroshetz. My name is Joe Breen. I’m a Program Official in the National Institute of Allergy and Infectious Diseases. And I serve on the NIH ME/CFS Working Group with Dr. Koroshetz and Vicky Whittemore, in particular. And I’m actually the program official for one of the three collaborative research centers that I want to tell you just a little bit about.

The consortium was awarded at the very end of September. So the centers are really just starting to ramp up. And there will be three, what we’re calling collaborative research centers, where they’ll do research and then one data management and coordinating center that has slightly different but overlapping goals that I’ll talk about in a second.

An important aspect of the whole network is that they will include community engagement and involvement of ME/CFS advocacy groups and individuals with ME/CFS, which is an important aspect of the program. And also another major feature I think that I want to mention is that the intention is that the centers will develop collaborative projects to truly start to develop a network and increase the amount of work in this area.

As I mentioned, the grants will be managed by NINDS as well as one by NIAID. The three centers, one is located at Cornell with the principal investigator Dr. Maureen Hanson. And the major goal of the center in Cornell is to identify ME/CFS-specific changes in the physiological and molecular responses to exercise that will include things like brain scans to help uncover the roles of inflammation, immune dysfunction, and other pathways, and to really communicate these findings to other ME-CFS researchers and the public. This center is based in Ithaca but has collaborators at Ithaca College as well as the Boyce Thompson Institute.

The second center I want to tell you a little bit about is called the Center for Solutions for ME/CFS. The principal investigator is Ian Lipkin. It’s at Columbia University. And Dr. Lipkin is utilizing clinical samples and will continue to search for the involvement of viruses and bacteria that may play a role in ME/CFS, something he’s been involved with for a long time. And he’s one of the leaders in the world in this area.

And he’s also looking to use cutting-edge technology to look at genetic analysis as well as to identify metabolites that may be involved, really to help understand what’s happening with the disorder, but also to potentially develop a diagnostic if we can get a signature, for example. The Lipkin center at Columbia was awarded by NIAID and I’m the program manager for that particular award.

The third collaborative research center is led by Dr. Derya Unutmaz at the Jackson Labs in Farmington, Connecticut. And we’re very fortunate that he’s on the phone with us today, so he’s going to tell you a little bit more about his center so I won’t spend any time about that because he can certainly say that better than I. Dr. Koroshetz has already mentioned the title.

And really, the last component is a very important one, the Data Management Coordinating Center, which the PI is Dr. Rick Williams, Research Triangle Institute in North Carolina. But he also has some ME/CFS experts at Johns Hopkins involved as well as members of the patient advocacy organizations to help with those efforts and really coordinate so that the output of this program over time, the data that’s generated at the program, will be available to the public and can really help to standardize so that it’s useful across all three centers, both for the collaborative projects as well as the individual projects.

And these centers actually have clinical cohorts attached to them that are really spread across the country from, for example in the Columbia Center, from Stanford, as well as clinicians in New York proper, as well as Salt Lake City. As does Dr. Unutmaz, who can tell you about his center himself.

And this program was launched in late September. NIH has invested about $7 million at this point for this first year. And if you want more information about the specific aims, for example, of the centers, you can look at the NIH press release about it. Or you can look at and find more information about the centers.

And at that point, I’ll turn it over back to Dr. Koroshetz.

Walter Koroshetz: Thanks, Joe. I’m sure we’ll have questions and we can expound further on the really, I think, historic group now that’s forming. And for any group to work collaboratively, and that’s the purpose of the consortium, you have to speak the same language and in science terms, those are called Common Data Elements. So the data that’s collected on patients has to be standardized so that you can compare one site to another. And Vicky will talk a little bit about the progress we are making in that sphere. Vicky?

Vicky Whittemore: Thank you, Dr. Koroshetz. This is Vicky Whittemore and I’m a Program Director at NINDS and working with Drs. Koroshetz and Breen on the Trans-NIH ME/CFS Working Group.

And one of the projects that we’ve undertaken in this last year together with the CDC and our contractor EMMES is to develop what are called Common Data Elements for clinical research on ME/CFS. And the goal of this project is to develop common definitions and standardize the reporting forms and other instruments that are used in studies of individuals with ME/CFS and it’s really to help the investigators to conduct research through the development of uniform formats by which the data can be collected, analyzed, and shared across the research community.

So, we’ve been working with 13 different working groups that cross the domains of ME/CFS from autonomic function, neurologic/cognitive, and CNS imaging to fatigue, pain, et cetera. And these working groups have been composed of clinicians, researchers, and individuals with ME/CFS and advocates who have worked together in each of these areas to develop these common data elements internally within each of their working groups.

And so the stage we’re at right now is that they’re finalizing, each of the working groups are finalizing their work packet or their documents, which will then be shared internally between all of the working groups between now and the middle of December, at which time they will be posted for public review and comment through the middle of January.

And then at that time, we will take all of those comments and make any necessary revisions to the common data elements before then releasing version 1 of the ME/CFS common data elements. And as you can imagine, these common data elementsneed to be flexible and change over time as we learn more through the research, as we discover that one test or one way of doing things is more valid than another with the population.

We will be posting some FAQs and overview of the process of developing common data elements on the NIH ME/CFS website soon. So watch for that. And we look forward to getting feedback from the community on the work that all of the working groups have done.

So at this point, I’ll turn it back to Dr. Koroshetz.

Walter Koroshetz: Okay. Very good. So now I wonder if Derya could talk to us a little bit about what he sees as the goals and aspirations for the collaborative research centers going forward. Derya?

Derya Unutmaz: Sure. Well, hello everyone. First, I’d like to say that I’m very excited to be part of this really amazing group of program officials at NIH and my other colleagues at the other centers. And I’m very happy to participate in this call.

So as mentioned, I’m one of the principal investigators of this collaborative research program located in Jackson Laboratory in Farmington, Connecticut. Just a very brief intro to myself, I have a medical degree. I don’t see patients, but I consider myself a human immunologist. I’ve been studying human immunology for the past 25 years in the context of HIV and other chronic diseases. And I was a professor at NYU School of Medicine before moving here about three years ago.

And I became interested in ME/CFS about four years ago while I was in New York, through Dr. Suzanne Vernon and Cindy Bateman. They introduced me to this disease. Actually, Suzanne reached out to me. I believe she was at the Solve ME/CFS organization at the time. She had heard about our immunology work. We’ve been doing profiling of HIV patients and cancer patients.

And she said would I be interested in looking at the immune system in high detail as a pilot project of a group of patients that they have stored. And I said sure, I’d love to do that. She sent me about 20 subjects at the time, and honestly, I wasn’t expecting to see anything major because in human population, you know, 20 is not a big sample number. There’s a lot of variation from donor to donor.

And what we do is we analyze hundreds, I would say dozens or even hundreds of different subpopulations of immune cells, their functionality in the blood. And that kind of reflects, we still don’t understand the details, but it’s sort of a reflection of how well your immune system is working, if there’s something being perturbed, but it varies from donor to donor. So, you know, 20 was a small number.

But to my surprise, we actually saw quite profound differences in these patients’ immune systems compared to the controls. And that’s when I really was interested in the disease. And to make a very long story short, we initiated a collaboration when Suzanne moved to Bateman Horne Center, together we had an R01 grant funded. We’ve already recruited about 200 patients for that grant and now we’re just beginning to recruit patients for this center.

So let me tell you a little bit about our goals very briefly. We have two major goals for the center. As Walter mentioned, one of the goals is to try and to find molecular biological correlates of the disease. And I think this is a very important aspect so that we can link the biology to the symptoms that obviously could be used as biological biomarkers to diagnose disease, to stratify patients. But also importantly, we want to understand disease mechanisms.

What we know, things are going wrong in the immune system. There’s data on the microbiome and metabolomics, but we don’t know how these things connect to each other, which is the result, which is a consequence. So by looking at these three different biological parameters, the immune system in a very high detailed fashion, as I said, we profile dozens of different subpopulations. We trigger them to see what sort of functionality they have. Is that being compromised in patients?

We will collect stool samples from patients and determine thousands of different species of bacteria that live in all of us. And it’s turning out to have an extraordinarily important impact on our biology and our immune system and involved in many different disease processes and we think also in ME/CFS.

And of course, the metabolism, this is everything from sugars to lipids to fats and proteins, everything that we take in and what our body produces to maintain our biology, our energy. We think there’s probably a disturbance there, too.

But the challenge is, we will generate lots of data sets as well as the other centers. How do we put this together? How do we create networks that will reveal potential targets, perhaps, that could be used to bring back the disturbed immune system or other mechanisms to normal so that they would be therapeutic targets? And that’s our, perhaps, even more important goal.

And we hope to do that by performing many computational analyses. When I say computational, using biostatistics, using bioinformatics, and more novel techniques called machine learning to analyze. So the computers help us analyze these data in a meaningful way and create these what we call topological networks.

And so we’re very fortunate to have one of the leaders in the field, Peter Robinson. He’s been involved in creating what we call clinical ontology for rare diseases, again linking clinical phenotypes of these rare, genetic diseases to their genetic mutations. Now he wants to apply that to ME/CFS. And as Vicky mentioned, I think once we have these common data elements where there’s a uniformity in both the clinical and perhaps even biological markers, we can pool data from other centers, other investigators and really try to create this network to reveal what is going wrong here.

And lastly but not least - and I can tell you more details about the patients and so on but I want to leave that to the question part. I do want to mention I was very excited when this RFA came from NIH that the community outreach is a very important aspect of this, as we’re doing right now. I am personally very passionate about this.

My motto in research has always been the patient is always right. I’ve studied humans for the past 25 years in various disease contexts and we learned a lot by looking at their immune system and trying to translate some of the results that we find to the clinic.

So I feel this is a very important aspect of it, both for the community, but also for us as researchers. As we’re learning from the patients, we can sort of direct our path where to get input and sort-of signposts to see where we can go with the biological research.

And in that regard, we are collaborating with a company called where they have patient tracking software. We’ll be announcing that in the next year and open it worldwide so anyone can participate. We can collect clinical data. We can track various aspects of the patients. And I think that’s going to be extraordinarily useful again to stratify the disease.

We also have plans soon to launch a blog where we will both chronicle our progress as well as others. We’re even planning a YouTube channel with some educational videos as well as informative interviews. And I’m also very active on Twitter. You can follow me. It’s Derya_ in Twitter if you’re interested.

So I’ll leave it there and leave time for any questions.

Walter Koroshetz: Okay. Very good. Thanks so much, Derya. And I think we can open up for questions now. So for either of the speakers, happy to see if we can help. Can we have the first question, please?  

Coordinator:    Thank you. If you’d like to ask a question, please ensure your phone is unmuted and please press * 1 and record your first and last name clearly when prompted. To withdraw your request, press * 2. One moment please to see if there are any questions.

Our first question comes from Eileen Holderman. You may ask your question.

Walter Koroshetz: Hi, Eileen.

Eileen Holderman: Thank you. Hi. This is Eileen Holderman. I’m an advocate. Thanks for allowing me to speak. I have a question for Dr. Nath. There was some controversy in the patient community when Dr. Nath presented at the CMRC Conference by putting up a slide that said Team Tired announcing his investigators that way.

And besides the offensive title for that, I think the more concerning aspect was that it indicated to many of us in the community that NIH might be studying patients with chronic fatigue the condition, not ME, the neuroimmune disease. Because it would be like putting a slide up for the study of diabetes that says Team Thirsty or tuberculosis, Team Coughing.

So could you reassure the ME community today that the NIH is indeed studying ME and mostly knows the difference between chronic fatigue the condition and ME, the neuroimmune disease? Thanks.

Avi Nath: Well thanks very much for bringing that up. First of all, let me sincerely apologize for that slide. And I do understand. I have received a lot of communication from patients. I have apologized to everyone who has written to me. And I want to apologize again publicly. So I’m very terribly sorry for that.

I do understand the sensitivity between the issue of fatigue and malaise and the importance of studying the right patients, because if you don’t study the right patients, you’re going to garbage in, garbage out. Right? So I think that’s extremely important.

So what we’ve done is and have put together a committee of five adjudicators who are recognized experts in the field of ME/CFS. And so when we collect all the data after the first admission of, you know, one week worth of data on them, that goes to everybody. And unless there’s unanimous decision amongst all five, we don’t bring that patient in here.

So considering all the challenges that are there in, you know, making an objective diagnosis, studying the right patients, we’ve gone to extreme lengths to make sure that we do study the right patients. So I want to reassure you that yes, we are aware of these issues and we’re doing the best that is humanly possible to do so.

Walter Koroshetz: Thanks, Eileen.

Eileen Holderman: Thank you.

Walter Koroshetz: Can we have the next question?

Coordinator: Our next question comes from Cort Johnson. You may ask your question.

Cort Johnson: Thank you. Dr. Nath, yeah, I was wondering where we are on the timeline for your study, if patients are being brought in for the second round of tests. And when do you see this, I know it’s probably quite a while, but when do you see yourself completing this study or if before you complete the study, do you see yourself being able to speak about any results you’re finding? Or stuff like that.

Avi Nath: Sure, Cort, thanks very much for that question. So as you know, as I mentioned earlier they’ve brought in about 26 people now. And every week there’s a new individual. So you know, depending on the schedule of the patients when they can come in and when they cannot come in, we will be bringing in patients for the second visit and the first and they’ll be intermixed in there.

As far as when we can finish the study, our capacity is to be able to handle one individual a week. So the 80 that we planned, so 80 weeks, but sometimes patients cancel at the last minute, sometimes there’s holidays, people fall sick, all kinds of things happen. So give and take those unforeseen events, you know, that’s the duration it’s going to take to complete the study.

And then it takes time to analyze the data. We’re collecting huge amounts of data, so it’s going to be a while.

So I’m just as anxious as you are to try and see if there are things that we can still put out from the patients as they’re coming through. The major parts of the study, you know, all biostatisticians will tell you, you don’t want to analyze because as soon as you start making comparisons between smaller populations and then you’ll just keep changing your beginning over and over again as you keep adding more people. So you don’t want to do that.

There are certain aspects that we are learning about these patients that I think about the interview process, the process of what we learn of bringing these patients in and there are very interesting things that are coming out. And we’ll be delighted to share some of those as we gain experience with it. So yes, some bits and drabs will come out. But I think the major parts of it will probably wait until the end.

Cort Johnson: Thanks.

Avi Nath: Thank you.

Walter Koroshetz: Thank you very much, Cort. Yes, can we have the next question please?

Coordinator: Our next question comes from Sophia Becker. You may ask your question.

Walter Koroshetz: Hi, Sophia.

Sophia Becker: Hi, everybody. My question is for Dr. Derya. And I was hoping that you could possibly explain in a little more detail the differences that you saw in the immune system of the initial 20 patients that you mentioned in your comments. Thank you. 

Derya Unutmaz: Sure. So actually, initially it was the 20 patients but as I mentioned, we’re now close to 200 patient blood samples that we have collected in the last year and a half. We’re still in the process of analyzing data, but a lot of the, you know, remarkably some of the things that we’ve seen in the 20 patients is highly reproducible.

So to get to your questions, what we saw, what was very striking was, we study a subset of immune cells called T cells. Now, you can imagine T cells as sort of the generals or the managers of the immune system. They send a lot of commands and if they are perturbed, many other parts can go wrong. And they obviously recognize infectious proteins and respond to viruses and pathogens.

So specifically, we observed that the functionality of these T cells, they secrete what we call cytokines. And this is the way they send these commands to other cell types. And there are, you know, a couple dozen different cytokines that these cells can produce, and depending on the conditions, there will be a different set.

And the interesting part was that some of these cells that produced some of these cytokines were greatly perturbed in the sense that they were either too low or too high. Without going into too much detail, we think that as some of these functional T cell populations actually correlate with what’s going on in the gut in the microbiomes.

Because some of these specific subsets that were so perturbed go to our mucosa, especially to the gut mucosa, and they’re there to check on, you know, the trillions of bacteria on the other side of the border to make sure that they can recognize only the pathogens. And if, you know, we don’t know why this is happening, whether it’s the destruction of the microbiome causing it or the immune system is destructed and that’s causing the changes to the microbiome and that’s actually something that we’re looking at.

There were other changes, but these were quite striking. And as I said, we have so much data that we’re still analyzing and I’m sure we’ll see additional features.

But the cool thing is that, you know, we know a lot about these cell types. We’ve been studying them in the lab for many years and you know, that gives us an idea about in terms of disease mechanisms and also potential therapeutic targets because these cells are also involved in other diseases, autoimmune diseases, chronic inflammatory diseases. And so there are lots of immunological modifiers that are being developed. And so that was quite exciting. And thanks for asking. It’s a very important question.    

Sophia Becker: Thank you. Can I ask one more follow up question?

Walter Koroshetz: Sure, yes.

Sophia Becker: So if I understand correctly, it looks like the T cells might be disrupting the gut microbiome. Is that correct?

Derya Unutmaz: I wouldn’t make that claim.

Sophia Becker: Okay.

Derya Unutmaz: As I said, we don’t know which is the cause. It’s conceivable that the microbiome is the initial trigger or the immune system is disrupted because as you know, many patients acquire this after infections, viral infections, and so that change in the immune system now is not able to regulate the microbiome as efficiently and perhaps that’s affecting the changes.

But, you know, we don’t want to say causality at this point. And I thinkthis is one of the focuses of the center, is trying to get into that exact question and it will have both microbiome samples and we’ll analyze the same T cell populations to see if there is, if we can establish that link.

Walter Koroshetz: Okay.

Sophia Becker: Okay. Thank you.

Walter Koroshetz: Thank you very much. Thank you, Sophia. Can we have the next question?

Coordinator: Our next question comes from Denise Lopez-Majano. You may ask a question.

Walter Koroshetz: Hi, Denise.

Denise Lopez-Majano: Good afternoon. Thank you very much. Several federal reports going back as far as I can remember as the state of knowledge at NIH in 2011 and as recently as the P2P workshop have prioritized the need for NIH to work with the research community on establishing consensus on a research case criteria for ME.

But now, NIH and CDC are concluding that more research is needed before this can be done. The CDE initiative isn’t doing this and actually allows for any definition to be used, even if it doesn’t require hallmark criteria such as PEM and cognitive impairment. This to me seems as though it only muddles things.

The IOM was really clear that PEM is mandatory and that Fukuda includes people who do not have ME. And there’s plenty of other evidence that makes this abundantly really clear, that PEM is mandatory.

Given all of this, why is NIH not conducting an effort with researchers in the community to reach consensus on what case definition or definitions, plural, should be used in research? Why is NIH not calling for case definitions that require at least the core inclusion of PEM and cognitive impairment as is recognized by the IOM, the CCC, and the MEICC? Thank you.

Walter Koroshetz: I think I mean, it’s interesting to consider the best way forward here. And so I think there is always a tension between standardization and constriction of the research. So in general, what we ask people to do, and we will be doing this in the consortium, is for the group to come up with characteristics that they will all use in common to characterize the patient.

And I think that one thing to note is that the patients may be in different stages so that, you know, a very kind of stringent criteria that throws out say, early stage patients, may not be helpful if you’re looking, you know, particularly at the condition of, what goes on after that initial event that leads to ME/CFS where different than when you’re studying a chronic population where you are looking at a confined group. There, I think the standardization and characterization of patients may be more helpful.

But I think what we’d like to do is to have the science drive these kind of questions as opposed to coming up with a convention which is, you know, I think important that the definitions be standardized so that people know what they’re talking about, but not necessarily coming down on one definition saying you can only study this one patient group. Because I think that may prevent us from seeing things that are really important in this condition.

So I agree with the point, but I think that for the research, NIH generally in all cases it’s not really in the position to be prescriptive and say, you know, this is what you have to do. We really leave it up to the scientist. But we are in this instance pushing them to do this in a collaborative fashion to avoid what’s happened in this past, which is one definition for one study, another definition for another study and then you really can’t combine the data.

So for instance in Derya’s discussion, you know, we have the opportunity now to know whether, you know, all the sites in this collaboration are going to see the same kind of T cell abnormality in the patients as described by Derya. And that I think is what we’d like to do, is have the science drive this question.

So I hope that’s helpful. I don’t know if anyone else wants to add anything else. Derya, would you want to talk about that at all?   

Derya Unutmaz: To say a few words, I completely agree and it’s very important to realize, you know, earlier in my brief introduction I mentioned there is an incredible heterogeneity in the human population. If you look at the immune system, the microbiome, metabolism, all of us have certain set ranges.

And, now that gets even more complicated when you are trying to group, subgroup a complex disease. For example, in our study where right now we’re focusing on what we call early-onset disease. And my clinical collaborators define it as, you know, having ME/CFS in the last three years. And the biological markers might be quite different in that early stage. And our goal is to actually follow them prospectively over the next four, five years to see how things change and are modified.

And again, I think the very important point here is that we have to stratify. The clinical symptoms may look very similar, but I’m almost convinced that there’s different underlying triggers. There are different underlying biological disruptions that lead to the similar type of symptoms. And so I think, you know, you’re trying to classify those from the start without the discovery, could be detrimental.

So we really need to have an unbiased discovery approach. And then as you said, you know, see what others are repeating, what type of patients these biological effects are seeing, and then start to come up with very more precise definitions.

Walter Koroshetz: Denise, is that helpful at all?

Denise Lopez-Majano: It is. But one of the questions that Dr. Nath raised in my mind was if you’ve got adjudicators on the clinical study who are verifying that the patients have ME, shouldn’t we have something similar with every other study that goes on in this disease?

Walter Koroshetz: Well, that’s a good point. Yes, that may be very helpful. You’re right. So I think that’s for this pilot we’ll learn from that, I think, yes.

Denise Lopez-Majano: But having something comparable in terms of knowing that we’re really studying people with ME is incredibly important. My sons have been sick for a dozen years.

Walter Koroshetz: Wow.

Denise Lopez-Majano: This is rough.

Walter Koroshetz: Yes.

Denise Lopez-Majano: This is really rough. They need help. Every patient needs help. I wholeheartedly agree that we need to study early-onset patients, patients who have been sick for less than three years and follow them. We also need longitudinal studies. We need so many more studies in every patient group. And I also would like to know what NIH is going to do about that as well. Thank you.

Walter Koroshetz: No, I think that’s really important. And you know, I just say that you know, from the point of view of NINDS and looking at the research landscape and this disease and other diseases, the advances come step by step. And one of the problems that we oftentimes see is when people try to solve the entire disease state in one project.

It’s just the disease is, specifically ME/CFS, so complicated that I don’t think that on the scientific side that this is going to be, you know, a magic bullet that comes down within the next couple years that solves the problem. I think this is going to be a battle that we’re going to have to just win, you know, one step at a time.

And to that point, the centers that we have funded are, you know, I think a big step but it’s only one step in that battle. And our aspirational goal is that this will galvanize researchers around the country to become interested in this condition.

So as people probably know, NIH has an open-door policy for people to submit grants. And most of the money that we fund our science with goes out to what we call these investigator-initiated grants. So NIH is not a top-down organization. It’s a much more bottom-up organization. And we do need, you know, throughout the country, you know, scores more people working in this field.

And so I think the future is bright in the sense that I think we’re off on the right footing, but this is just the beginning. And we need a real army to come in and try and work on this problem.

So okay. Why don’t we go to the next question?

Coordinator: Thank you. Our next question comes from Mark Camenzind. You may ask your question.

Walter Koroshetz: Hi, Mark.

Mark Camenzind: My son is severely ill with ME. Can’t even open his eyes. Can’t talk. He’s on a feeding tube. And we have to get going on this sooner versus later, so we are not, some people I know have had this 55 years. So first we need ICD codes that make sense for the long term, so we can track this disease. Norway is tracking it and if CDC doesn’t track it, CDC will not track it until states track it. States can’t track it until they get some guidance from NIH and CDC working together for rational ICD codes so we can track it. Otherwise, we could have an epidemic like they had in the 1930s for a Los Angeles hospital, 1950s in London, 1980s in the US in New York and California, Incline Village and you wouldn’t even know it. That’s just absurd that CDC’s not even having any tracking of significance for this disease. 

And then we do need researchers in this, but that takes funding. So we need like 250 million dollars a year or least 200 million dollars a year of funding. So NIH needs to get more centers going. And I do appreciate Dr. Koroshetz’s help on this. But NIH needs more funding, not just seven million dollars a year, which is a great start, but pretty pathetic considering the huge disease burden of this disease.

So how can NIH work with CDC and IDC to get tracking codes so states can start tracking this so then we know if there’s epidemics and then we know a little bit more of the geographical influences or any sudden outbreaks? Thank you.

Walter Koroshetz: Okay. So as to that question, Mark I think you’re entirely correct that you know, we need better data on what’s going on across the country. The billing codes are the best thing we have in this country and certainly not research grade material, but it’s the best we can get.

So yes, we’d be very interested, and we will bring this up with our CDC colleagues to see how that would work. My recollection is that the ICD codes are a complicated business and determining when you would get a new code. I did do this once before for stroke, so I know it’s possible. So we’ll definitely bring that up.

And again, I must say that…

Man: May I have your attention. May I have your attention. Brief test…

Walter Koroshetz: We have a fire drill

Man: …of the fire alarm system has been concluded…

Walter Koroshetz: Sorry about that.  

Man: There is no need to evacuate the building.

Walter Koroshetz: That’s good news.

Man: Brief test of the fire alarm system has been concluded. There is no need to evacuate the building. Thank you.

Walter Koroshetz: And again just to mention that, you know, the story of your son sounds terribly tragic and, you know, we feel terrible that we don’t have something at this point in time that’s helpful.

Mark Camenzind: Well, we need more than four centers, also because California has no center. And so we need places for patients to show up and actually be seen and doing research because there’s thousands of experiments going on continuously that are not controlled, and that’s a waste of research information. If we had more centers to track in Utah, California, other states with interest at least we would have a lot more data.

And then we need to start doing clinical trials, possibly steramine through UCSC or even hyperbaric oxygen, a simple molecule. You breathe it every day. And it shows promise for fibromyalgia. Turkey did studies showing promise for chronic fatigue syndrome, and yet we see no studies in US. So why are we getting approved drugs like Ampligen in Argentina, studies in Turkey, studies in Norway? We need more clinical studies in the United States.

Walter Koroshetz: Right. Yes, I agree. Okay. Thank you very much. And we want to go to the next question, please.

Coordinator: Our next question comes from Rebecca Taurog. You may ask your question.

Rebecca Taurog: Hi. Yes, I’m a person with ME/CFS. I also am a former biochemist, former assistant professor. I have applied for and gotten NIH grants in the past. And I’m aware, and also have applied for and not gotten them. I’m aware that often the NIH funding lines are really tight.

And I heard of or watched an interview with Koroshetz and the head of I think the Solve ME in which there was a discussion, and I think sort of a lot of things have pointed to this in this current discussion, suggesting that there aren’t enough good grants being presented to the NIH, being submitted to the NIH for funding around ME/CFS.

I have trouble imagining that something in the say, top 20th percentile or top 30th percentile, is not worth funding and yet right now we still have really, I mean, I’m appreciative of the funding that has, you know, that we’ve doubled funding since ten years ago, but as Mark mentioned the disease burden, no one has actually put the number but I think people have done studies that show the disease burden to be something that would suggest something closer to like 200 or 250,000 per year or million dollars per year from NIH and we’re getting like 11 or 15. That just seems really low.

So I’m just wondering what is keeping that sort of funding level at its current state. And are there grants that are say in the top 50th percentile that are probably high quality and should be funded but that are not being funded right now?

Walter Koroshetz: Well, I think you’re right, that NIH runs out of resources and leaves lots of good science on the table because we can’t fund it. And as you know, it’s a very American system where it’s a matter of how many people submit highly competitive grants and there’s not a, you know, all the diseases we take care of are terrible, so it’s not like you can say one is worse than the other.

So the system is really run by how many people are submitting the good grants. And the problem I think in ME/CFS is that the number of investigators, of highly trained investigators in the space, is still very small. And in the system that NIH has, the solution is to keep growing the science pool so that they’re competing against the other diseases.

Now, I’d also say that we have at NINDS about 400 different diseases. Many of them are fatal diseases and none of them get the money that is equivalent to the burden of disease. So you can look at say the RCDC codes for different diseases and see just exactly what these other conditions are getting. But the system as it is really depends on the science that drives the funding and not a top-down decision.

Rebecca Taurog: And what you’re suggesting then is that there, I mean, earlier you’re saying the science drives it and we’re not getting enough good grants to fund in ME/CFS, but we all know that there are grants that are not being funded that are by top scientists.

I also think one thing I heard you say in that interview that stuck with me pretty strongly is that yes, I understand there are lots of other diseases. Some of them are not suffered by two million people in this country. They’re much more rare, even if they are fatal.

But you were pointing out that studies in other fields, therefore other diseases, might give insight into ME/CFS. I’m a basic researcher and I totally appreciate that point, but I think that the opposite is also completely true and maybe even more so, because ME/CFS is just so much more so systemic and, you know, within the patient and also so much more complex, it’s unlikely that we will be able to tease out much by studying other diseases that you know whereas if you understand the system, then you might be able to actually apply what’s known about or what’s learned about ME/CFS to a lot of other diseases.

So, I mean, I understand that you have a lot of different things pulling at you. What I’m trying to ask is what is preventing the greater, like how would we get ME/CFS funded at a higher level? I mean, if you compare us to MS, they get, you know, six or seven times, at least eight, I don’t know, times more funding than we do and the disease burden is just greater actually for ME/CFS. So that’s where I feel like you’re dodging sort of the basic premise of my question.

Walter Koroshetz: No, I don’t want to dodge. I think it’s a long conversation, but I would say that we don’t fund any, we have no centers or RFAs for MS research. So we have them for ME/CFS research because we need to stimulate it. The multiple sclerosis field, which was quite small, you know, when it started in the ‘70s is now, you know, what we want the ME/CFS field to be at.

But the only way we can do that is to get really good scientists interested in it. And as you know, with a payline of 12th percentile, you need to submit, you know, eight grants to get one. And that’s, you know, I think we’re resource-limited in this country. And I think a lot of really good science does not happen. But there’s not much you can do about it without more resources.

But I think for you, I think your passion, you have to make that infectious. Be persistent and get other people you know, in your camp doing this science and competing for grants. That will guarantee that ME/CFS research will advance at the pace you want. So thanks for that. I think we have one more question.

Margo Warren: We have time for one more question. I know there are a lot of people still on the line waiting to ask questions. So please send us your remaining questions to the email address brain info, all one word, at ( Or go to the NIH ME/CFS website which is and click on Contact Us to submit those questions. So now, let’s hear the last question.

Coordinator: Thank you. Our final question comes from Barbara Cottone. You may ask your question.

Walter Koroshetz: Hi, Barbara.

Barbara Cottone: Hi. Can you hear me?

Walter Koroshetz: Yes, great.

Barbara Cottone: Yes. I’m a physician. I’ve had this disease for 21 years. And I don’t think that casting the kind of broad net metabolically that’s dominating research right now is going to produce anything, because over the course of time, and even initially, it’s been clear to me this is an autonomic neuropathy that is simply poorly defined.

So my question would be, there are two centers in the United States that study autonomic neuropathy. One I believe is at the Mayo Clinic.

Walter Koroshetz: Right.

Barbara Cottone: And the other is in Vanderbilt in Tennessee.

Walter Koroshetz: Right.

Barbara Cottone: And I’m wondering if the NIH has had any discourse or any kind of exchange of the possibility of them doing research in this disease. I know Vanderbilt is interested. I’ve had contact there directly. But I’m sure they could do a very focused study on this disease that would yield some very interesting results. So I’m just wondering if either of those centers have been on the radar in terms of researching myalgic encephalomyelitis.

Walter Koroshetz: Yes, definitely on the radar. And I guess we can’t as a government agency, we can’t speak for other institutions, but yes I know, I would say, with my Federal hat off, I agree with you totally.

Barbara Cotone: Thank you.

Avi Nath: Let me just add something to that. So we do have a huge autonomic component in our study in the intramural program.

Barbara Cotone: Yes.

Avi Nath: And so David Goldstein, who is an expert in autonomic dysfunction, he is really doing all of that. We’re also going to be doing skin biopsies to actually look at the autonomic nerve fibers. And Mike Polydefkis, who is at Hopkins, is going to look at those fibers there.

And there is a study at Hopkins. I think it’s in children with ME/CFS, that they’re looking at autonomic dysfunction in fairly good detail.

Barbara Cotone: Is that Peter Rowe?

Man: Yes, I think so. That’s the person, yes.

Barbara Cotone: Yes. I know he’s been doing some studies on neural-mediated hypotension and OIH. So I know there are studies on children. But I wish there would be more work on the autonomic nervous system in adults who have this disease because I think it’s primary, frankly, in what’s going on.

Derya Unutmaz: If I could just add to that. You know, I completely agree. This is very important. In fact, I think in general neuroimmune interactions are extremely important and I believe autonomic neuropathy is also potentially a immunological disease. So I completely agree.

But it’s important to realize that the biological systems are all interlinked. When we talk about metabolism, we wouldn’t be studying that in isolation. It would be how that affects the immune cells in turn how the immune cells would affect the nervous system, for example.

So trying to establish that. But I appreciate the point.

Barbara Cottone: Okay. Thank you for clarifying that. I appreciate it.

Walter Koroshetz: Okay. Well thanks so much everyone.

Margo Warren: Thank you so much. And just a reminder, a recording and a transcript of this call will be posted on the NIH ME/CFS website next week. Also a reminder about our listserv for updates at NIH. If you received a message about today’s call from the NIH ME/CFS Working Group, your address is already in our library. But if you heard about this meeting from a friend or in another way and you’d like to be added to the listserv, please visit the NIH ME/CFS website and click on Join our Listserv at the bottom of the left sidebar.

So thank you again for joining us today for an informative discussion. And I hope you have a great afternoon.

Walter Koroshetz: Thank you.

Derya Unutmaz: Thank you all.

Coordinator: Thank you for participating in today’s conference. Participants may disconnect at this time.


This page last reviewed on December 13, 2017