The NIH intramural research program has shifted all non-mission-critical laboratory operations to a maintenance phase in order to promote physical distancing and diminished transmission risk of COVID-19. Effective Monday, March 23, 2020, only mission-critical functions within NIH research laboratories will be supported.

NIH ME/CFS Advocacy Call - March 17, 2020

Coordinator: And thank you for standing by. For the duration of today’s call, all participants will be in a listen-only mode until the question-and-answer session of today’s call. I also would like to inform our participants that this call is being recorded. If you have any objections, please disconnect at this time. Thank you. I would now like to turn your call over to Ms. Gallagher. Thank you. You may begin.

Alissa Gallagher: Good morning. My name is Alissa Gallagher, and I’m from the Office of Neuroscience Communications and Engagement at the National Institute of Neurological Disorders and Stroke. On behalf of the NIH, I would like to welcome all of you to this morning’s telebriefing and to thank you for your interest in participating in this discussion with us today.

Dr. Walter Koroshetz, Director of NINDS, will introduce the speakers, each of whom will make some remarks, after which we’ll open the phone call for your questions. We’ll try to make our remarks brief so that we can answer as many questions as possible in the time that we have available to us this morning.

We also request that everyone ask only one question so that we can hear from as many of you as possible. Now, I’d like to turn over the call to Dr. Koroshetz.

Dr. Walter Koroshetz: Good morning. Can you hear me all right?

Dr. Leonard Jason: Yes.

Alissa Gallagher: Yes.

Dr. Walter Koroshetz: Great. Well, thanks, everyone for joining. These are I’m sure difficult times for everyone, but particularly for those with ME/CFS. And so, we want to just start off by wishing everyone the best in health as we try to get through this viral pandemic. And I’m sure that this has upset the plans of many people, including the folks here at NIH.

We are now all working from remote areas, and I actually have a - I think what is a common cold - but I’m home, calling into this conference; be careful not to let its contagious nature affect anybody else. And I apologize for my voice as we go through.

Now, as in the past, we want to, you know, let the community of both scientists and patients and advocacy organizations know about the research that we are working on and our grantees are working on, and also, answer questions from folks about the research and about NIH, and how NIH works.

We think that this is the best way of communicating on a regular basis with the community so that folks know, you know, what the up-to-date information is. Also, on these calls, we are looking forward to bringing in guest speakers, and today we have Dr. Leonard Jason from DePaul University.

And the speakers that we bring in are people who are really dedicated to ME/CFS research, and most of them have NIH grants to study ME/CFS. And so, you get to hear from the experts on what they’re doing and how they are thinking about the problem and trying to bring solutions.

We today had hoped that Dr. Nath, who runs the Intramural Program would be able to join us, but I think we understand that he is currently on the consult service in the hospital, and I don’t think he was able to get out of the hospital service today to join us, but we’ll get an update on the Intramural Program at our next meeting.

So, I think now what we’re going to do is move to updates. Dr. Breen from the National Institute of Allergy and Infectious Diseases will give an update on the Data Management in the Clinical Center in the Consortium. Dr. Whittemore will talk to us about updates from the Trans-NIH ME/CFS Working Group and implementation of the Council’s Working Group Report.

You may recall that at our Council meeting - I think it was, if I’ve got it right, it was in September - we had a presentation of the Working Group on ME/CFS to our Council, and now we’re working on those recommendations. Then we’ll move to Dr. Jason, and then we’ll have a Q&A. So, with that, let me ask Dr Breen if you want to give an update on the Consortium?

Dr. Joseph Breen: Certainly. Thank you, Dr. Koroshetz. I want to - my name is Joseph Breen, and I work closely with Vicky Whittemore and the rest of the NIH Working Group. And I want to talk to you a little bit about the progress that’s occurring at the three Collaborative Research Centers, and then the Data Coordinating Center.

So, as you likely know, that one of the Research Centers is at Cornell, and I’m excited to tell you that they’ve had a paper that was recently published in the Journal of Clinical Investigation.

If any of you participated in the previous call, I mentioned that we were getting excited at this stage of the CRC Network; that we anticipated that they would have peer reviewed work that would be published in the next intervening time, really showing that the productivity of a Center that was stood up, that took some time to get started, would really start to reap some benefits.

And I think that’s what we’re seeing, and I’m going to talk to you a little bit about a few of those that are now peer reviewed and publicly available and actually can be seen on PubMed and other ways to look at this kind of work.

So, the work by Dr. Maureen Hanson and colleagues showed altered T cell metabolism in cytokine associations. And this work is important, and this was shown in ME/CFS patients compared to controls because it shows that T cell metabolism is actually consistent with ongoing immune alterations.

Immune dysregulation has been seen for a number of years, but really understanding that its metabolism in the immune cells themselves was not previously demonstrated, and certainly not demonstrated to the level of detail shown in this study recently done by Cornell, which was published in December 2019 in the Journal of Clinical Investigation.

At the same time period, Dr. Hanson published a short report in a journal called Metabolites, showing there were differences in some lipid and steroid metabolism in ME/CFS patients compared to controls.

And this, the differences were more subtle, but this has been noted at least one other time in the literature, and I think it deserves further follow-up and further development of analytical techniques, actually, to get at this in more detail.

And I think it will add to the picture of trying to understand what’s happening with immune dysregulation and potentially some lipid metabolism. So, that’s from a basic science perspective, it’s all more understanding of mechanism.

In the Center run through Jackson Laboratories with Dr. Derya Unutmaz, they also have a recent paper that is under review at a peer review journal that is already submitted to the Bio-archives Repository, where it can be read by the public. And this paper is about the perturbation of effector and regulatory T cell subsets.

So, T cells are a specific type of immune cell, similar in some ways to the cells that the Cornell group was looking at. But this study was a little bit different and has really looked down into the types of subsets of these immune cells. And they see certain patterns that some cells, the activity goes down, while in others has gone up.

In particular, some T cells called T regulatory cells seem to be higher in ME/CFS patients - again, pointing to immune dysfunction, which may point out chronic inflammation, or a chronic response to inflammation.

And also - and they’re also looking at this in detail - some microbiome dysbiosis, which is another area that the Jackson Labs is really an expert in and is applying to this ME/CFS model. And I think, again, a better understanding of the immune dysregulation will help to point to mechanisms and hopefully identify some potential therapeutics.

And the third Research Center is Dr. Ian Lipkin. They have some work that’s recently been submitted for publication about, from the Plasma Proteomics Program suggesting an association between antigens, clonal B cells expansion and ME/CFS.

So, the previous studies that I mentioned were in T cells. And T cells are, in one sense, are the cells that turn on your antibody-producing cells. So, this would be a different kind of study. We’re looking at the B cells, which ultimately do produce antibodies.

So, I think the driving associations that are pointed out by the Lipkin group, I think, would be a novel contribution and again, highlighting that better understanding of mechanism will help us understand the etiology and the pathogenesis of this form of ME/CFS overall, and begin help us presumably to come up with a biomarker to measure it as well as design some therapeutics.

They also have ongoing projects collaborating between the three Centers, looking at different T cell populations, but taking into account the strengths of each of the Centers.

For example, the strengths of the microbiome analysis at the Jackson Labs, and then some of the metabolomics that’s present in several of the Centers, and I look forward to talk to you about that work in a future update.

And all of the Centers had multiple abstracts submitted to the International CFS Meeting planned for June.

The Data Management and Coordinating Center has been involved in activities to coordinate activities sharing data through, that are generated from each of the Centers and will soon be launching a way for the public to see that.

And really, I think that will be quite an unveiling, and is actually helping to organize even things such as meetings and collaborative projects between the three Centers and really improving the synergy. And I look forward to updating you on those activities in the future.

So, that’s the update from the Clinical Research Centers, the Coordinating Research Centers and the Data Management Center. Vicky?

Dr. Vicky Whittemore: Thank you, Joe.

Dr. Walter Koroshetz: So, Vicky, so you want to talk to us a little bit about the recommendations from the Council Working Group Report?

Dr. Vicky Whittemore: Yes, absolutely.

So, we had been working to put together a workshop that we were going to hold this spring to focus on discussions around clinical outcome measures, clinical, patient-reported outcome measures and clinical trials in ME/CFS.

But because of the situation, we’ve decided instead to move - and we just talked this through with the Trans-NIH Working Group yesterday, and we’ll be working with the NINDS Office of Science Policy and Planning to coordinate these activities.

But what we are planning to do is to put in place a series of webinars focused on several topics that were raised in the Report. And it addressed several of the strategies, and in particular, a lot of the issues focused in on the Appendix under Strategic Planning. So, really, to involve ME/CFS stakeholders in the discussion of these different areas that will then inform a research plan on ME/CFS.

So, that’s underway, and we will be reporting out on that as soon as we have those plans in place. In addition, we have continued to work with the Common Data Elements Oversight Committee to continue to modify and refine the common data elements that are in place for ME/CFS.

We are working with BioSEND, which is the NINDS-funded biorepository at Indiana University to put in, they now have all of the bio specimens from the study that was funded to collect samples on the originally funded, by the CFI Initiative and the Hutchinson’s Family Foundation.

So that all of those biospecimens will be made available from BioSEND, and together with the clinical data that was collected in conjunction with that study, which is currently being housed and cleaned at RTI as the Data Management Coordinating Center for the Network.

We have been working very closely with many investigators who have contacted us to talk about research grant applications they would like to submit, and also talking to individuals who submit grants. When they’re not funded, we work with them to talk through the discussion and the summary statement once when they’ve received the reviews back to help them with their resubmission.

And then, we’ve also – Andrew and I – have had several discussions with the Office of Training at NINDS around things that we can do and put in place to help the pipeline of young investigators in ME/CFS research, as well as to strengthen and improve mentoring in this area of research as well.

And so, a lot of these things are, as I said, in the works, and we will be rolling out a lot of information about our activities in the coming weeks, and especially around the planned webinars. So, stay tuned for more information. Thank you.

Oh, I forgot one important thing, I’m sorry. The Interagency Working Group. So, we have decided to partner with the CDC to put the Interagency Working Group for ME/CFS in place.

We’re working on getting the invitations for that Working Group out and are hoping to schedule the first meeting - again, because of the circumstances, likely a webinar - sometime in late spring or early summer. So, that is also moving forward.

But that’s all. I’ll turn it back to Dr. Koroshetz.

Dr. Walter Koroshetz: Thank you very much, Vicky. Yes, so it will be great for the agencies to be able to get together and talk about their research and coordinate. So, we’re really looking forward to getting that group together.

And I guess also, to mention yesterday, so NINDS and a number of the other Institutes belong to what’s called the Neuroscience Forum at the National Academy of Medicine. And yesterday we were able to get on the Agenda a very interesting session on what’s understood about how the brain, it involved, what circuits in the brain are involved in fatigue. So, it was kind of the neurobiology of fatigue.

And you know, so it’s heavily in, say, animal studies, people looking at the different brain circuits and creating fatigue models, trying to then develop medications that might actually improve fatigue in these animal models.

So, as science moves, frequently, there are discoveries in animal research that then leads to hypotheses to test in humans, and so I was quite impressed by the group. And also, we got a lot of people, both neuroscience academia and industry thinking about fatigue and its mechanisms. So, hopefully that, at some point, can translate into a benefit for the ME/CFS community.

So, I just wanted to bring that up.

And now, I think we’d like very much to turn back to Leonard Jason. He is the Director of the Center for Community Research at DePaul University in Chicago. And he’ll tell us about his recent work that was published in the journal of Child and Youth Care Forum, in which they did a very, what looked like an incredible amount to work to get at the prevalence of ME/CFS in children.

And then he’s also been awarded an NIH grant, again, on investigating ME/CFS after infectious mononucleosis.

So, we’re really pleased to have you here, Leonard, and please take the mic and give us a summary of the work that you’ve done and what you plan to do. Thank you.

Dr. Leonard Jason: Thank you very much. I appreciate the invitation. I very much appreciate 25 years of NIH funding for our ME/CFS research, which began in the mid-1990s with adult community-based prevalence research, and this work is now extended to youth.

ME/CFS significantly impairs various aspects of children’s and adolescents’ lives, including physical functioning, school attendance, and extracurricular activities.

One investigation found only 14% of adolescents with ME/CFS attended school regularly. Another study found that ME/CFS to be the most common cause of prolonged medical leave from school among adolescents.

Descriptions of ME/CFS in pediatric samples have often described the patient as being athletic, ambitious, upper middle class before they got the illness. These findings have some similarities to how adults with ME/CFS were described following the first generation of adult epidemiologic studies.

Previous studies in this pediatric prevalence area have found rates of about 2.7 to 1,900 per 100,000. However, many of these studies relied on physician referrals, which excludes those who do not have access to medical care and this exclusion may have reduced previous prevalence estimates.

In addition, not all prevalence studies included a physical examination in screening laboratory evaluation to exclude other diagnoses. In an effort to control for those deficiencies encountered in many of the prior ME/CFS epidemiologic studies, our studies collected data from a community based, ethnically and socio-demographically diverse sample, and provided test-positive and test-negative youth, medical and psychological examination.

We hoped these methods would generate a more accurate estimate of pediatric ME/CFS prevalence.

In the first stage of our study, we involved calling households in the Greater Chicago metropolitan area. As parents were contacted over the phone, we found out whether or not they had youth 5-to-17 years of age.

The pediatric ME/CFS screening questionnaire, which we developed, was administered to respondents to screen for ME/CFS-like profiles among children and adolescents.

Those with no exclusionary medical conditions who screened positive for either significant fatigue or school learning memory problems or had substantial reductions in functionings in three or more ME/CFS symptoms were considered screen-positive and selected for full evaluation. So, they had to have all those different characteristics to screen positive.

However, we also had screen-negative control participants matched for gender, age, ethnicity.

For Stage II of the Study, parents and youth who agreed to participate, met criteria, came to Lurie Children’s Hospital for structured psychiatric interview, psychosocial assessment and medical evaluation by Dr. Ben Katz. The parent and youth completed the pediatric version of the DePaul Symptom Questionnaire, the Child Health Questionnaire, the Autonomic Symptom Checklist, and the Fatigue Severity Scale.

We also had filled out the schedule for Affective Disorders and Schizophrenia for School Aged Children. This was separately given to the child and parent.

We screened 5,622 households and had data from about 10,100 children and adolescents. Of those who screened, we had basically 298 reported prolonged unexplained fatigue and additional symptoms. So, they all met criteria for what’s called a screen-positive. We eventually ended up working up 165 of these in the matched control group.

At the end of Stage III, a team of physicians were responsible for making final diagnoses. Two physicians independently rated each youth according to the ME/CFS case definitions of Fukuda, what’s called a pediatric criteria, modeled after the Canadian clinical criteria case definition and the more recent IOM criteria.

Reviewing expert physicians had access to all information gathered on each participant during each of the three phases of the study. The individuals evaluated for ME/CFS had to meet all three case definitions.

So, let me talk a little bit about the results now. There were no significant differences between screen-positive subjects and screen-negative, in terms of gender, race, ethnicity and age.

The prevalence of ME/CFS in the community-based pediatric population was found to be 0.75. That’s basically 750 per 100,000, or approximately 1 out of every 134 youth.

Females were found to have a higher prevalence rate of ME/CFS than males. The prevalence rates of ME/CFS were higher for Hispanic, Latino, and African-American individuals when compared to Caucasian youth. And those aged 14-to-17 had higher prevalence rates than younger children.

There were no significant differences found between participants with ME/CFS and controls with regard to gender, race, ethnicity, and age. Significant differences were found between participants with ME/CFS and controls in regards to the number of symptoms reported, duration of fatigue, fatigue reports and fatigue severity scale, autonomic symptom checklist and symptoms.

Most importantly, of the 42-youth diagnosed with ME/CFS, only 2, or 4.8%, so 2 out 42 is 4.8% - had been previously diagnosed with ME/CFS. Thus, most youth with this illness are not diagnosed.

So, let me kind of try to wrap this up and give you what I think are the important points. Substantially higher prevalence rates of ME/CFS were found for females, individuals from racial/ethnic minorities and older children.

Higher rates among minorities could be due to them having less access to adequate health care. Higher rates among older youth compared to the younger ones could be due to hormonal changes inherent in adolescents. Younger youth might also be exposed to fewer environmental and biological precipitating causal factors.

Conceivably, those who are older might be less physically fit or have more opportunities to experience other physical illnesses or stressors that can cause fatigue.

Most importantly, less than 5% of the identified youth with ME/CFS had previously been diagnosed with the condition. This finding is comparable with adult community-based findings regarding the majority of adults also not being identified previously. These findings point to the need for better ways to identify youth with the illness and to develop appropriate rehabilitation interventions for them.

The lack of agreed-upon case definition has complicated efforts to estimate prevalence rates of pediatric ME/CFS. The three widely-used case definitions were used in this study with diagnostic criteria ranging from a very broad perspective using the Fukuda to more stringent criteria of the CCC and IOM.

In the current study, individuals diagnosed if they met all three case definitions. Thus, we used a conservative strategy to accurately identify cases. The CCC pediatric criteria was found to be the most stringent.

In summary, we determined the prevalence of pediatric ME/CFS in the community to be about 0.75%. In addition, it appears that females, those from Hispanic, Latino and African-American ethnicities have higher rates than Caucasians. Of particular importance, over 95% of identified youth had not previously been diagnosed.

Autonomic fatigue and symptom data suggest that those who have this illness have significant and multiple impairments, and thus represent a high-risk group that needs to be both diagnosed and appropriately treated.

Since receiving considerable media attention from this study, Cort Johnson of Health Rising conducted a poll that found that 44% came down with ME/CFS before age 18. While this is probably a self-selected sample, it is possible that adults with this illness did have the disease earlier.

The only way to really better understand that issue is to conduct a prospective study of individuals who are well and then follow them when they get ill with ME/CFS. We are engaging in such a study now with my colleague, Dr. Ben Katz. We have recruited a sample of about 4,500 college students and had them provide blood samples and fill out our DePaul Symptom Questionnaire and they filled these things out when they were well.

About 5% in college went on to develop mono, and we have now assessed those youth when they develop mono and followed them up at 6- and 12-month follow-ups - some of whom ended up recovering; some of whom did not.

Our new grant will allow us to follow up this important cohort into the next five-year period. And again, we appreciate the funding from NIH and NINDS for this work.

Studying youth and young adults might provide us with unique insights into the pathophysiology of this illness. Most research in our field has been on adults who have been generated from tertiary care settings with possible complications from other age-related illnesses.

Our focus on youth from demographically diverse samples that are unbiased by chronic illness or help-seeking might help us better understand autonomic, cytokine, metabolomic, genetic and other potential biological markers.

Thank you and look forward to answering any questions on the study.

Dr. Walter Koroshetz: Thank you very much. That is an incredible amount of work. Could you talk to us a little bit about the team that was assembled to accomplish this work?

Dr. Leonard Jason: Sure. You know, we have a physician, Dr. Ben Katz, who does infectious control at Northwestern and Lurie Children’s Hospital. And we’ve been collaborating on both the adults as well as the pediatric studies for many years.

But I would say he is really one of the key factors in our work, and really taking the field of psychology - which I’m a member of - and him in medicine really is nice. We think of it as translational research.

Of course, we have a team of physicians, one psychiatrist and two who are non-psychiatrists, who basically are involved in looking at the individuals and also making a diagnosis of whether they have ME/CFS or not. And so, we have a team that basically does the clinical evaluation.

We also have, you know, lots of interest in this type work from other professionals who are both graduate students becoming trained in our fields - my field is clinical community psychology.

And also, we have individuals who are undergraduates who get some training in research methods. We had literally hundreds of volunteers from DePaul University, students who actually helped us make the thousands of phone calls, which were generated over multiple years, so they had opportunities to get some research training and generating samples.

So, those are some of the key people, but certainly there are other folks that, you know, we’re now working with on a new grant. So, yes, it’s a very multi-disciplinary approach for our work.

Dr. Walter Koroshetz: Yes, I mean, just looking at the - correct me if I’m wrong - but it sounds like there were 147,900 phone calls and 43,045 phone numbers were reached. That is a tour de force, I think.

Dr. Leonard Jason: Well, thank you, and certainly, you know, what we wanted to do was to try to generate a sample that didn’t necessarily come through, you know, like the tertiary care settings. And to do that, one needs to sort of go out to random community samples, and it is expensive type research. It takes a long time. But I do think the results we get from those types of samples might be different - very much so - from those who end up coming into tertiary care settings.

Dr. Walter Koroshetz: And let me ask; do you have the capability and the consent to follow up affected individuals that you identified - I think 165, or something like that?

Dr. Leonard Jason: Yes. And that’s what we’re actually right now in the process of recalling the actually the 44,500. And we’re trying to, and we’re actually - you know, as well as the ones that were brought into Lurie Children’s Hospital.

We’re also calling the other folks. And if those folks became symptomatic in the five-year follow-up, we will bring them in and evaluate them. So, we will be able to actually look at the emergence of new disorders, new ME/CFS, as well as the maintenance of ME/CFS in these two very large samples.

But of course, the ones we are most particularly interested in are the ones that we have - yes, so yes. This is the mono study for college students. And that particular group, we are following up.

The epidemiology study, which is, again, I think a very valuable sample, we are – we’ve wanted to do a follow-up data on them, and we do have permission to do that, but we don’t have funding to do that at this point.

Dr. Walter Koroshetz: It sounds good. I would say, “Write a grant.” It sounds like a great population to follow.

Dr. Leonard Jason: Yes.

Dr. Walter Koroshetz: Well, very good. Well, thanks very much. I’m sure there will be questions from the folks listening on the phone.

Before we go to questions, I do want to mention that we received hundreds of holiday cards, letters and photos from the community in December, and I wanted everyone to know that, you know, we feel strongly, as do all the letter writers, that there needs to be more research on this disease, and the folks on the phone in our Institute and in NIAID, where Joe Breen is, are working hard to make that happen.

And we do understand that there’s terrific suffering going on there out in the world where folks are suffering with ME/CFS. And although we’re making progress, it is way too slow, and we’ll do everything we can to try to encourage investigators such as Dr. Jason, who you heard here, to kind of devote their career to better understanding this illness.

And I guess before we go, I think we need to say something - although I’m not sure how much information we can give you - about the potential interaction of COVID-19 with ME/CFS. And Dr. Joe Breen from the NIAID talked to you a little bit about the new findings that have been coming out in ME/CFS, and I wonder if Joe could - I know he can’t give you, you know, medical answers, but at least give you what the expert opinion is on COVID-19 and ME/CFS intersection. Joe, would you be able to address that?

Dr. Joseph Breen: So, thank you, Dr. Koroshetz.

So, what I can say is that when we actually this week had a call with the Collaborative Research Centers, they are intensely aware of this situation with COVID-19 and how that’s affecting ME/CFS patients and could potentially involve more. And they’re understandably quite concerned, as they’re still recruiting patients for the ME/CFS studies that I mentioned, and others that are still ongoing.

I think that the reality is that we don’t know a lot yet. I think that worldwide, research teams are collecting a tremendous amount of information. Much of that has been turned around and made publicly available through websites such as those at the CDC with coronavirus.gov, which will take you to a number of resources.

And then the WHO, the World Health Organization, has a similar website for COVID-19 with information that’s more globally based. And there are a number of ways that this is being tracked.

So, as of yet, we don’t have research connections between COVID-19 and ME/CFS, but I think I just want to let people know who are listening that certainly researchers and clinicians are paying attention. And of course, right now, there’s priority, as is quite public, is on testing, available therapeutics, and development of vaccine.

But I think right behind that are recruitment of longitudinal studies which from cohorts from all kinds, sectors of society which will also include ME/CFS sufferers.

So, I think at this point, I think it’s quite public about advice on things to keep yourself healthy, and I would recommend that people visit those websites, the CDC and the WHO websites, for the most up-to-date advice, and know that, you know, I described the research progress on these immune phenotypes and it’s - and you realize that, you know, that’s relevant to COVID-19.

But at this point, the best way to keep yourself informed, because these are research projects, is to really look at the coronavirus site on the CDC and the WHO. And of course, I’d be happy to take questions when we get to that stage.

Dr. Walter Koroshetz: Well, thank you, Joe.

Alissa, I think we can go to the questions now. Is that correct?

Alissa Gallaher: Yes, I think we can go ahead and get started.

Coordinator: Thank you. We will now begin the Question-and-Answer session of today’s call. To ask a question, please press Star-1, unmute your phone and record your name. Your name is required to introduce your question. To withdraw your question, please press Star-2. Again, to ask a question, please press Star-1. Thank you. It may take a few moments for the calls to come through.

Denise Lopez-Mojano, your line is open.

Denise Lopez-Mojano: Good morning. Thank you very much for this very informative call. And in particular, Dr. Jason, thank you for your presentation and for your work. Your recent paper on the prevalence in pediatric populations highlights the very sad state of underdiagnosis disparities in research populations and clinical populations.

I have so many questions for you, but let me start with did you examine any of the biological indicators in this prevalence study for the people involved?

Dr. Leonard Jason: Yes, we actually have blood samples in deep storage, and slide samples in deep storage. And we also, as was mentioned, would be most interested in follow-up studies. We think it’s a really unique sample, and we think that those biological samples could really help us to make predictors.

So, far up to now we haven’t been successful in being able to secure NIH funding, but we hope maybe that thing will change in the future.

Coordinator: The next question comes from Terri Wilder. Your line is open.

Terri Wilder: Hi, thank you. Dr. Jason, thank you so much for your presentation. It’s been really helpful for me to read about it as I reach out to medical students at medical schools.

My question actually is about something a little different. On March 4th, activists with ME interrupted Dr. Francis Collins’ opening statement in the House Appropriations LHHS Subcommittee Hearing to demand that the NIH take urgent comprehensive action to send the crisis of ME that’s been growing unchecked for more than three decades.

Dr. Collins responded to the protester’s demands by saying, I quote, “I do want you to know that the condition ME/CFS, chronic fatigue syndrome, is of great concern to the NIH.” He added that he, quote, “Would like very much to talk about it at a later point.”

He never did talk about it in the hearing, despite the fact that the Chair of the Subcommittee gave him permission to do so. This was a huge missed opportunity to educate and raise awareness about this disease.

The NIH has neglected ME for 35 years and has ignored the repeated recommendations of Congress to quote, “Expand ME/CFS efforts, including provide set-aside funding for ME research consensus on the ME case definition, incentivize researchers to enter the field.”

Furthermore, the 2021 budget request note on ME says nothing about providing any new funding for ME initiatives, and the projected 2021 spending on ME is exactly the same as 2019, so that means that not only no new funding this year, but no new funding in the next year.

We really need more than concern from Dr. Collins and the NIH. We need comprehensive action now. The protesters who were interrupting the subcommittee hearing are part of a growing movement of people with ME who are demanding justice via the NotEnoughforME Campaign.

You already mentioned part of that campaign, which was the 500 holiday cards sent to Dr. Koroshetz.

The activists on March 4th put their debilitated bodies on the line to tell Dr. Collins to stop the excuses and fund ME research so the millions missing can return to their lives. Our community needs the following questions answered by the NIH.

Why didn’t Dr. Collins include our disease in his opening remarks to the Committee? He named many other diseases and could have certainly named ours.

And two: Why did he dismiss this opportunity given to him by the Committee Chair to share information about our disease and our needs to this Committee? We are very upset about this and need these questions to be answered.

Both Dr. Joe Breen and Vicky Whittemore know who I am and can send me his answer via email along with a written plan on how he will include our disease, ME, when he gives testimony to the Senate regarding the NIH budget.

Dr. Walter Koroshetz: Okay, thank you very much. I think, you know, as I mentioned earlier, you know, here at NIH, we are, I think we are on board with the request that ME/CFS funding be much more robust. We don’t think that at the current level it’s – it would almost take a miracle to solve ME/CFS. We need folks like Dr. Jason and probably maybe 500-to-1000 more to dedicate their careers to ME/CFS.

And that’s the goal that we’re working towards. And then we need to do that with the patient groups. NIH is a funding organization, but it’s really the patient organizations that motivate people like Dr. Jason to devote their careers to research on a particular topic. And I think it’s happening, but it’s got to happen much faster.

With regard to Dr. Collins, I had heard about the hearing. I can certainly bring up to him your points. I would say, however, that the added action on the part of NIH was really something that Dr. Collins instigated and triggered. So, all the work we’re doing now, I think, is a result of him charging the Institutes to move much faster and more aggressively into ME/CFS research.

And so, he is your champion; no question about it. Now, he has lots of things on his plate. But I will guarantee you that ME/CFS is an important issue for Dr. Collins. And it has been for, you know, for a number of years now.

And so, he is a champion that I think we need to give him all the ammunition we can to kind of get the message out to the Congress and to the science community that we really need a much bigger push in this area.

So, thanks for that, and I think we’re pretty much in agreement on the goal, and the question is just how do we get there.

All right. Can we have the next question, please?

Coordinator: Yes. Our next question is from Whitney. Your line is now open.

Whitney: Hi. I think it’s fair to say we’re all thinking about coronavirus right now. And what we need, Dr. Koroshetz, is for you and the NIH to understand how deeply connected this massive crisis is with ME/CFS.

I am very encouraged that Dr. Breen said researchers are listening to our concerns. As you know, many of us developed ME/CFS after a viral trigger - often during widespread outbreaks like this.

But we just don’t have enough research to show direct causes. Personally, my ME was triggered by H1N1 swine flu in 2009, and I feel as though nobody cared that I never got better. So, coronavirus has huge implications for our community and this disease.

I was thrilled to see the fast action in the news that the NIH has already started clinical trials on a potential vaccine. And while prevention is important, what will be done to study and treat the people who may contract this virus and remain ill from it like we have?

The study Dr. Jason described is a great model for what we should see with coronavirus. So, my question is, how do you plan to include people with existing ME/CFS and study links between ME and any potential post-viral fatigue syndromes that we could see resulting from coronavirus?

Dr. Joseph Breen: Walter, do you mind if I take this question?

Dr. Walter Koroshetz: Joe, are you going to take that question?

Dr. Joseph Breen: Yes. Thank you. I’m sorry. I had some audio problems.

So, I think that right now, as you mentioned, that the emphasis is on getting clinical trials started with therapeutics that we already have that were developed for other RNA viruses that might be helpful in this case.

And that’s quickly then being followed up with the vaccine studies, which have actually already started, as you mentioned, which is really an unprecedented timespan.

I think that it’s likely that we’ll see studies that are making connections to other chronic diseases, and particularly chronic viral diseases that will follow up on that. But to be honest, the priority right now are those two areas because of the immediate needs in the county.

Through discussions that we’ve had with researchers, I think the kind of projects that you mentioned will surely follow, but I think the priority and the fact that we’re right in the middle of this pandemic right now, the priorities are the ones that I mentioned.

And I anticipate - and I know from talking to researchers even in the Collaborative Research Centers where they’re recruiting patients - that they’re thinking about these connections, because it’s vitally important. But it’s going to follow the therapeutics and the vaccine studies because that’s where efforts need to go right now in the short term.

Again, if you want to see those priorities, that they’re all publicly available at the resources that I’d mentioned earlier.

Dr. Leonard Jason: Can I mention something also, along these lines? Lisa Petrison, who is one of the experts on mold – M-O-L-D – and how it might be really causing this illness has been in touch with quite a few patients that have indicated to her that they seem to be – have gotten actually sick over the last couple weeks.

And she has begun to put together a survey which I’ve had a chance to look over. And she will be distributing it very soon. It’s a very comprehensive survey.

And it actually would be kind of interesting to actually collect some data on this issue with both people with ME/CFS as well as other illnesses and to see how they’re doing, and then possibly be able to re-administer a questionnaire at a later time to see if anyone who filled it out initially now is sick, and they weren’t sick the first time.

So, both those who are sick versus those who aren’t could be probably put together relatively quickly. And as I said, that survey has been almost developed and will be, you know, will be issued very soon. So, I think that is a very positive development.

Dr. Walter Koroshetz: Thank you very much. Yes, I hope that COVID doesn’t lead to an increase in ME/CFS, but I suspect that, as the caller mentioned, it’s something that we should be prepared for.

Unfortunately, at this point, we don’t have a preventative therapy. And then, I’d also add that the intramural program in ME/CFS is looking particularly at folks who develop symptoms after characteristics of a viral infection.

So, this idea of a viral infection - infectious mono, Lyme disease, for instance - triggering immune response that then goes on to ME/CFS is front and center in folks’ minds. But we always hope that it won’t happen with COVID-19, but I think we, as you mention, we should be ready for that.

Next question, please.

Coordinator: Claudia Carrera, your line is open.

Claudia Carrera: Hi. Dr. Koroshetz, I’m glad to hear you acknowledge the real scope of the research that we will actually need to achieve key outcomes like the treatment - like you said, in the range of 500,000 researchers instead of a few dozen.

I completely agree. But what you and Dr. Collins are currently doing is going to take decades to get us there. And you have announced zero new funding for ME/CFS on this call. That is not how a champion treats an urgent priority, especially in the middle of a crisis.

Now I want to say, I spoke to you almost a year ago on last year’s spring community call, and at that time I identified eight different existing NIH funding mechanisms you could use to provide set-aside funding for ME/CFS.

You said several of these were good ideas and that you would look into them. I called on you to secure at least one new funding stream for ME research and to hire at least one new admin to work on the ME portfolio by the end of 2019.

But now several months into 2020, you have taken zero steps toward either of these crucial capacity-building actions. Yet you have been telling the media that the NIH - just like they’re telling us - about how much the NIH cares about ME/CFS. You’ve been telling the media that the NIH has doubled funding for ME/CFS research in recent years.

I want to be very clear for everyone on this call about what has actually happened with ME funding here. Throughout the 1990s, there were either two or three ME Research Centers funded at all times. And the total level of funding in 1995 when you take inflation into account was almost the same as it is now; just $2 million less.

In the last few years, you have not doubled ME efforts and resources at NIH. You have reinstated funding that was cut from ME research in the early 2000s, and we are barely getting more NIH resources now than we were 25 years ago. That is not enough for ME.

But even worse, your FY 2021 projected spending reveals you are not even planning to gradually increase this amount year-to-year because your projection for 2021 spending is exactly the same as what you spent in 2019. So, even you don’t expect that the Centers and the PAR you’re going to put out are going to increase your spending.

So, look, we all know that science takes a long time, even when you are throwing everything you have at it, like with the coronavirus. So, at this level of funding, it will likely take us another 30 years to get to the point of having treatments for our community. Maybe 50 - that is unacceptable.

And if you disagree with that time estimate, Dr. Koroshetz, please do let us know. It would be great to hear when it is that you expect that we will actually be reaching the milestone of a treatment if we follow the current path of $14 million a year in funding.

We refuse to let another generation waste away in dark rooms for decades, especially following this coronavirus. And we need biomarkers and treatments in the next few years, not the next few decades. And you and Dr. Collins need to do what it takes to make that happen.

So, my question is about RFAs and PARs. In the October advocacy call, five months ago now, Dr. Whittemore said we would need RFAs to address several of the issues that were raised in the Q&A. Yet you have announced zero in this call. And now of course, the coronavirus crisis makes this even more essential and urgent.

So, you have to quickly inject funding into ME research, and one way to do that is by expanding the Collaborative Research Center Network, which is what you said you wanted to do when you first announced the current Centers. You said this is a seed. It is – we know it’s very little. We know it’s small. What has been proposed by the CFSAC was 12 Centers, I believe.

And you said it was going to be expanded. So, do that. You have to go increase the funding for the three existing Centers and you have to fund an additional cohort of Centers. And you have to do it now to accommodate the studies we’re going to need of post-coronavirus development of ME/CFS.

And I’ll just say this is an urgent crisis and you cannot squander this opportunity to finally figure out how this disease takes hold on our bodies. And you have the money to do it - $8 billion for coronavirus, okay?

Now in the same October call, Dr. Whittemore said that the unfunded PARs would be released soon - hopefully very soon. But it has now been almost a year since they were approved in the May NINDS Council Meeting when you told the Council that these - sorry - Vicky Whittemore told the Council that these PARs were urgently needed and intended as a rapid measure, while further RFAs were being developed.

And it’s been a year since that point. Those PARs need to be released yesterday. And at least one of them needs to include a call for coronavirus-related ME research, in my opinion.

I don’t want to keep hearing that you’re getting held up by coordinating with other Institutes or getting NIH approval. These do not even have funding attached. If Dr. Collins cares about the community, he will make them happen, like by the end of this month.

So, release what is ready now, now. Make whatever else needs to happen for the rest, happen, in keeping with the urgency of the current crisis.

And so, my question, Dr. Koroshetz, is when will the first PARs finally be released? When will you increase funding for the current CRCs? And when will you issue a new RFA to fund additional Centers? And please don’t tell me soon. I want specific months by which you plan to take these urgent steps. Thank you.

Dr. Walter Koroshetz: Well, that was, I think, you know, all very cogent arguments, and I think that if you email us, we’ll get back to you with the specifics in terms of the plans.

And I just wanted to add, for folks who don’t know, that the vast majority of NIH funding goes to what we call investigator-initiated grants. So, three times a year, anyone can write an NIH grant. And they get reviewed, and then they get funded depending on the meritorious nature of the grant.

And the review panel who does that is a review panel of ME/CFS experts. So, we are always open for business for applications. Now if we don’t get applications, we cannot fund research. Our problem at the current time is that the number of applications is terribly, terribly small. So, the goal, if we’re going to change the playing field, we need more people to work on ME/CFS. And that’s a decision that every scientist must make. NIH cannot make that decision for other people.

So, I just want to emphasize the grants that come in on ME/CFS actually get funded at a rate that’s either the same or better than the other grants that we see. And as you mentioned, there were many years of very poor funding, but the funding situation is much better now. So, that a large number of really good applications will get funded, and all the Institutes will bend over backwards to fund good applications in ME/CFS research.

And as you say, there are other mechanisms that we can pull; levers that we can pull, such as the Consortium lever. And there, you know, we are looking carefully at what other levers to pull. But if we don’t get the number of applications to go up, none of those levers are really going to solve our problem.

There are temporizing Band-Aids, but we really need - and that’s why we’re on this call; that’s why we put the effort in to bring young scientists in to have meetings about ME/CFS to try to encourage people to come into the field.

And I think that’s what we need to do together as a cohesive team and encouraging folks to come into this area is the most important thing at this point in time. And we do feel terrible that it’s so slow. And we are open to any suggestions to kind of move that faster.

So, I understand the anxiety, and I agree with it. And we’ll continue. We’re not giving up. I don’t know if Dr. Jason, if you wanted to talk to folks a little bit about why you decided to work on this topic, and maybe give some sense of, you know, what it takes either for us or others to motivate people to work on ME/CFS.

Dr. Leonard Jason: Sure. Sure. I’m happy to say a few words. First thing, as we know, you know, it’s a very competitive process. And you know, most grants do not get funded from people like myself that submit them. So, we need to recognize it’s challenging. And one has to be really persistent to ultimately get the funding.

And I do think that if, again, just you know, I think this is such an unusual opportunity to understand as, you know, we heard in this call that there are immune markers and possibilities for understanding this chronic illness could really have implications for all types of different types of coronaviruses.

And that, I think, the reason this is such a critical time for investigators like myself and others from outside of NIH to get interested in this is because we know that a certain percentage of people, based on some of the Australian research from multiple viruses and different types of pathogens, there’s a certain percentage of people who don’t recover.

I’m particularly interested in the Epstein-Barr virus, but we know that some people seem to continue to be impaired six months, a year, several years later, and into their lifespan.

So, what’s happening right now is such unique opportunity to basically find a cohort and to sort of see the manifestation of the immune system, because what we can find from coronavirus might have incredible implications for, you know, the types of other viruses or other types of precipitants that might be causing this illness.

So, yes, this is a time of unequaled opportunities for researchers to get involved. And I applaud, you know, the individuals who kind of talk about RFAs, you know, are probably being phased out to other types of mechanisms that are going to be PARs. And those possibly could be targeted for all types of incredibly important work, going forward.

So, yes, I do think that this is an important time for us to be working on these issues, and I do think that the insights we learn from this basic ME/CFS research will have incredible implications for many other types of illnesses that are affecting our citizens today.

Dr. Walter Koroshetz: Thank you very much. Alissa?

Alissa Gallaher: Yes, so we’re at the top of the hour, so we’re going to go ahead and close the call. I apologize that we weren’t able to get to all of your questions. So, those of you who might still be waiting to ask a question, you can feel free to send them to braininfo@ninds.nih.gov, or simply go to the NIH ME/CFS website and click on Contact Us to submit those.

A reminder that a recording and transcript of the call will be posted to the NIH ME/CFS website soon. And I’d also like to remind you about our listserv for updates from NIH. To be added to this listserv, please visit the NIH ME/CFS website at www.nih.gov/mecfs and click on Join Our Listserv at the bottom of the left sidebar. Thanks to all of you for an informative and thoughtful discussion. We wish all of you good health and a good afternoon.

Dr. Walter Koroshetz: And thanks very much, Dr. Jason, for joining us, and I hope, as Alissa said, everyone please be safe out there. Thank you.

Coordinator: That concludes today’s call. You may disconnect at this time. Hosts, please stand by for your line count.

END

This page last reviewed on April 6, 2020