USA: NIH National Institutes of Health news - latest ME/CFS webinar 14 Jan 2025

Read the latest (US) National Institute of Neurological Disorders and Stroke [NINDS] Director’s Message from Dr. Walter Koroshetz: Advancing Research on ME/CFS.
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Summary: inoffensive, relatively short piece from Koroshetz, talking up NIH progress on ME/CFS (roadmap, intramural study), biological mechanisms mentioned a few times and no whiff of effort preference/BPS ideas.

Last paragraph:
A number of factors, including the lack of a research effort that is scaled sufficiently to meet the public health problem, has led to understandable frustration in the ME/CFS community. We hope that this is a turning point for ME/CFS research. New findings from the intramural ME/CFS study and from additional NIH-funded studies, the development of the Research Roadmap, and research focused on infection-associated chronic conditions such as Long COVID, should move us closer to understanding ME/CFS and identifying treatments to help those affected by the disease.
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It's almost an apology.
 
Inoffensive. But it doesn't mention funding and whether NIH plans on providing funding to advance research.

What's needed is NIH funding designated specifically for ME (RFAs). Otherwise, researchers are in a very tough position of first being reviewed by grant reviewers who don't understand the disease and then competing against grants from established diseases and researcher networks with far greater funding

The messages from NIH staff so far suggest NIH will not be providing this kind of funding and instead will focus on low-hanging fruit.

Dr. Koroshetz note said the trans-NIH ME/CFS group - a group internal to NIH - will "identify how best to implement research to move the suggestions forward." Waiting to see what they come up with in terms of strategic direction, focus, and funding. So far, I am personally disappointed that neither the intramural study or the roadmap specifically focused on PEM and learning more about its underlying pathology.
 
Yann04 said:
I found that post to be quite dismissive and problematic. I’d recommend others to read this which points out the other side of the story:
https://thesicktimes.org/2024/03/19...for-a-retraction-of-the-nih-intramural-study/
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My takeaway after reading Health Rising, this sicktimes blog, and listening/watching half the symposium so far: the main value in this study seems to be trying to test as much as possible.

People talk about them wasting money, not enough participants, not severe enough, not enough comorbidities. But if the researchers believed that the best course of action was to just throw everything at the wall and see what sticks, I can see how they would have to make many difficult compromises.

Coordinating the testing of forty people using dozens of invasive, stressful, state-of-the-art techniques, I would assume, is extremely expensive. Every additional person makes it more expensive, and lowers the budget for testing variety. The more severe the patients, the harder to make sure they can all even make it through the whole trial.

Comorbidities add confounders that would be a big deal with such a small sample. If they have as homogenous a group as possible, they increase their chances of a signal getting through. Something they demonstrated when they separated the small sample into two even smaller, but more homogenous groups, of males and females, and showing larger differences in multiple markers.

And I personally really like the method of testing as much as possible that has never been tested or proven before. There are thousands of potential markers and any one of them could be a hidden treasure. They have the money to efficiently test lots at once. Let the smaller labs follow up on the promising ones.

"Effort preference" is a weird one. What they say about it in the symposium makes sense - their explanation for what it means and how they never intended it as a psychologizing term. I haven't read the paper so I don't know if what they say now doesn't jive with what was in the paper. But if most of the paper is looking for, and finding, lots of biological abnormalities, would they really still be trying to squeeze in a subtle "it's all in your head"?

And I don't know much about how reasonable their conclusions are - I know the sicktimes blog talks about complaints - but again, I think the main valuable output of this study is loads of data that they are fully releasing to the public on mapMECFS. Anyone is free to analyze the data and put forth better conclusions. I think they said Nancy Klimas is excitedly adding all this data to her existing ME data in her "supercomputer" to hopefully produce new findings.

I'm sure there are actual issues and things that could be done better. But I think people are attributing too much malice and ineptitude to the researchers. My impression from watching them is that most/all of them actually care about the pwME, care to do this in the best way they can, and are motivated to find treatments as soon as possible.

Edit: I do wish they had been able to control for deconditioning, as many or all of these markers could very well turn out to be caused by deconditioning. But if they're limited by resources for sample size, I can see how it'd be an issue to divide the groups down further to healthy and deconditioned controls.
 
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A number of factors, including the lack of a research effort that is scaled sufficiently to meet the public health problem, has led to understandable frustration in the ME/CFS community.

Lack of research effort is not the only major reason why patients are frustrated.

I understand the need to not get too mired in the past and recriminations, and to not jump the gun on adequate exposition and accountability for it all. But it really can't just go on being ignored or misrepresented either. We are way past that point.

This is one of the most disturbing stories of sustained and extremely serious institutional abuse by any authority in the last 50 years in the so called developed world. It requires a much more detailed acknowledgement of the full story, the historical and still very much active consequences for patients, and the ongoing barriers that are making it so difficult to turn around.

Including, in particular, the seriously substandard methodologies we are still being subject to from the psychosomatic wing of the profession. Until that is fixed it will be a giant toxic anchor dragging on any progress and the long overdue restitution of patients' reputation.
 
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6/6/24, Neurology Journal: "Dr. Jeff Ratliff talks with Dr. Avindra Nath about new research related to post-infectious myalgic encephalomyelitis/chronic fatigue syndrome”

Dr. Nath: "In our study, we did a very, very detailed neurological work-up. We looked at the blood, spinal fluid, cytokines, metabolomics, every omics you can think of...functional MRI's, autonomic testing, we looked at the effects of exercise on them..muscle biopsies, mitochondrial function. The advantage of doing a very detailed phenotyping study, is that now if you do find some immune abnormalities, you can now try to correlate with these other physiological parameters that no one's been able to do before."

"So, that provides us with a very rich dataset. When we did that, it was very clear to us, that these patients have a defect, a primary defect, is in B Cells. They don't switch from IgM to IgG very easily. When you don't see that switch taking place, you need the B cells in order to get the T cells mature, to respond to an antigen. So, the T cells are now unable to respond to an antigen and they will get exhausted. So you have a situation with abnormal B cells, with exhausted T cells, and when those two happen, what happens is that your innate immune responses gets triggered. So then you get all these cytokine production, macrophage activation - and that produces that sickness type syndrome. And so, I think those are the cascade of events, immunologically, that I think are leading to the syndrome that we see.”

“The underlying hypothesis, that if you have a defect of the immune system, what you’re unable to do is really clear the antigen…so what I’m not saying is that, let’s say it's a viral infection, I’m not saying that they have fully replicating virus still persisting in them, what it is could be bits and pieces of them, that are still hanging around and they haven’t been able to clear them. I said there’s T cell exhaustion. That makes me think that their getting exhausted because their trying to fight against something but their unable to clear it. If that’s the case, one possibility, would be to reverse the T cell exhaustion. So, one could consider a clinical trial with checkpoint inhibitors. That’s one possibility. A second possibility is that you can suppress the innate immune activation, if you stratify your patients accordingly. There you have multiple choices. So, depending the cytokine profile that is elevated, you can block TNF, IL-1 or IL-6. We have various medications that can do that. You can nonspecifically block cytokine production and have various types of medication for that as well."
 
forestglip said:
Currently a Q+A about LC clinical trials.
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Walter Koroshetz: "The patients with ME/CFS are incredibly frustrated by the lack of interest by physicians and taking care of them. So for years, they have been fighting a perception that people don't think they have anything wrong with them, and it's "in their head" quote unquote. So hopefully long COVID has gotten rid of that. After what we've seen from the long COVID pandemic, this is clearly an immune disorder, there's no question about it. You know in ME/CFS community, we don't have the workforce. We talk about pain research being tough, ME/CFS research is way tougher, just not the workforce. But now we have hundreds of people working on long COVID, and the hope is that they see this disease as something that they can pursue as a scientific career. That would be great, for long COVID, ME/CFS, whatever the next infection."

Unknown person 1: "Monica, just to mention, that as we discussed before, we do hope to have a major investigator and patient participation meeting by early in the fall, to review directions going forward."

Atul Butte: "I think there is still a lot of skepticism about long COVID. It's a tragedy, actually, that there is skepticism, but I sense there is still skepticism. But there's also skepticism about RECOVER itself. I mean I don't need to point out the articles. Monica, you were mentioning you put office of the director into this. Is there a new oversight of RECOVER through the office of the director, of the whole project? And the speaking perhaps out of turn there is maybe a little more of a request for more transparency as how the funds are getting spent, I think is fair to say. Is there a new oversight, is that what you meant by bringing in OD into this?"

Monica Bertagnolli: "Oh no, transparency is fair. We really need to be transparent about how we're spending our funding. I think I can very, very easily defend what RECOVER has done. I mean, again, you've just saw it, right? I mean, these enormous cohorts, understanding of this disease. I've also seen the list of really amazing manuscripts that are going to start to emerge over this summer, finally. I think people will start feeling much better about RECOVER, its first wave, once the manuscripts really start flowing, which they are definitely coming. And I think the other lesson is now, the infrastructure has been built, and it is an infrastructure on a scale that has never happened before, in research, ever. So I can certainly defend all of that. The reason for moving it into the OD is to get everyone together to now take a look at everything we have learned and then come up with a strategy for moving forward. RECOVER's not moving into the OD, I misspoke. RECOVER is definitely not moving into the OD. What's moving into the OD is this big planning activity. And why did I think that needed to land in the OD? Because of how critically important this is, as an initiative, that is doing things that we've never ever done before, with the ability to engage an even broader community. So: only planning. And then we'll move forward with the next wave of research coming out of what we've learned with the first wave.

And I want to signal to the community - I think that's also really important - we're signalling to the community that we are going to, we built an amazing infrastructure, and now we're going to sit down and take a very deep look at what we've learned and then come up with a plan to go forward, and be very transparent about that, and be very clear about that. And frankly we can be that way now, because we've learned so much."
 
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forestglip said:
Unknown person 2: "I think there is still a lot of skepticism about long COVID. It's a tragedy, actually, that there is skepticism, but I sense there is still skepticism. But there's also skepticism about RECOVER itself. I mean I don't need to point out the articles. Monica, you were mentioning you put office of the director into this. Is there a new oversight of RECOVER through the office of the director, of the whole project? And the speaking perhaps out of turn there is maybe a little more of a request for more transparency as how the funds are getting spent, I think is fair to say. Is there a new oversight, is that what you meant by bringing in OD into this?"
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Anyone know who this is? First name might be "Asul".

IMG_20240614_122505.jpg
 
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Dakota15 said:
@forestglip - Possibly Atul Butte, Chief Data Scientist at University of California Health. He live-tweeted the conference, and I think (?) that picture is him.

https://x.com/atulbutte
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That's him, thanks! "Atul Butte" fits with the blurry name on the card in front of him.

I like that he was calling for transparency and pointing out that people have issues with RECOVER. Will be following him.
 
(mods feel free to move where most appropriate)

'House Energy & Commerce: 'Chair Rodgers Unveils Framework for NIH Reform, Requests Stakeholder Input’

'Stakeholders who wish to submit any feedback on the framework or provide additional thoughts, ideas, and suggestions for reform can do so by emailing NIHReform@mail.house.gov by August 16, 2024.’

——

Covered in STAT News: 'NIH needs reform and restructuring, key Republican committee chairs say’

'in some instances, they have been intentionally deceptive about research being conducted with taxpayer dollars. NIH officials have consistently resisted transparency…’

'As with all taxpayer-funded federal agencies, the NIH has a duty to responsibly steward resources. Both before the Covid-19 pandemic and increasingly since it, the NIH has held a more visible role as the nation’s preeminent public health research agency.’

'Given concerns raised during and after the Covid-19 pandemic and the need to maximize the impact of taxpayer money, it is imperative to build a stronger and more accountable NIH.’

'To that end, the House Energy and Commerce Committee is unveiling a framework of potential reforms, including streamlining the 27 current NIH institutes and centers into 15 revised ones that better align with overarching goals, missions, agendas..’

—

Science: 'House lawmakers float plan to overhaul National Institutes of Health'

'Republican leaders of two committees want to streamline agency’s 27 components, tighten policies'

'both House & Senate committees are proactively collecting feedback from stakeholders’
 
(part 2)

Sharing from the 22-page official plan release, on Page 17:

'"Recently, there have been several instances of missteps in the NIH’s grant review and prioritization processes that have prevented successful research outcomes. For instance, the NIH’s RECOVER Initiative, which launched in 2020 with a $1 billion-plus budget, continues to face criticism from patient advocates, researchers, and lawmakers. The original goal of the initiative was to understand Long COVID causes, symptoms, and the long-term impact; define the risk factors and impacted populations; and identify possible treatments. However, there have been clear and avoidable mistakes, including initial mistakes to hire scientists more focused on a “big data” approach over experts in post-acute infection syndromes, as well as a misguided focus on observational studies, as opposed to clinical trials focused on identifying tangible treatments. As discussed above, RECOVER also suffered from the longstanding institutional pattern of awarding funding to researchers and institutions with prior established records and funding histories with the NIH, possibly to the detriment of researchers specialized in this space, but who were at an earlier stage in their career."

--

'The ideas and challenges presented in this framework are intended as a starting point and foundation to foster further discussion to keep America at the forefront of biomedical innovation. Please submit any feedback and additional thoughts, ideas, and suggestions for reform, in writing, to NIHReform@mail.house.gov by August 16, 2024. The Committee looks forward to working with interested stakeholders as we identify opportunities for reform now to build a stronger NIH for the future."
 
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Also if any are interested in an op-ed on the NIH after the reform proposal, STAT News is interested in community thoughts (sent out to their subscribers today)

“What do you think? Is the NIH doing its job, or does it need to be reformed and restructured? Weigh in by sending an email to first.opinion@statnews.com, and please put "NIH" in the subject line.”

Adding these STAT News op-ed guidelines, if anyone does end up pursuing.

(Have strong feelings or thoughts on the NIH ME Intramural Study? Or on RECOVER Initiative? Here’s a possible productive opportunity to channel that - you can write-in what degree you agree with or disagree with reform/restructuring, or all-things NIH oversight etc. Or of course on transparency, fair commensurate funding levels, meaningful patient engagement, ability to make swift / adaptive progress, grant review and prioritization processes, etc)
 
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House Energy and Commerce Committee said:
The original goal of the initiative was to understand Long COVID causes, symptoms, and the long-term impact; define the risk factors and impacted populations; and identify possible treatments. However, there have been clear and avoidable mistakes, including initial mistakes to hire scientists more focused on a “big data” approach over experts in post-acute infection syndromes, as well as a misguided focus on observational studies, as opposed to clinical trials focused on identifying tangible treatments.
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As much as I support the committee's view that the NIH could usefully be reformed, I found this description of what is wrong with RECOVER rather odd. Epidemiological work, setting up registries and so on - that all seems fine to me. Actually, it was leaping into clinical trials of things like exercise that were a lot more of a problem. Maybe I'm wrong, I haven't been following RECOVER that closely, but that comment, and the RECOVER website too, make it seem like bad clinical trials weren't part of the problem.
 
forestglip said:
My takeaway after reading Health Rising, this sicktimes blog, and listening/watching half the symposium so far: the main value in this study seems to be trying to test as much as possible.

People talk about them wasting money, not enough participants, not severe enough, not enough comorbidities. But if the researchers believed that the best course of action was to just throw everything at the wall and see what sticks, I can see how they would have to make many difficult compromises.

Coordinating the testing of forty people using dozens of invasive, stressful, state-of-the-art techniques, I would assume, is extremely expensive. Every additional person makes it more expensive, and lowers the budget for testing variety. The more severe the patients, the harder to make sure they can all even make it through the whole trial.

Comorbidities add confounders that would be a big deal with such a small sample. If they have as homogenous a group as possible, they increase their chances of a signal getting through. Something they demonstrated when they separated the small sample into two even smaller, but more homogenous groups, of males and females, and showing larger differences in multiple markers.

And I personally really like the method of testing as much as possible that has never been tested or proven before. There are thousands of potential markers and any one of them could be a hidden treasure. They have the money to efficiently test lots at once. Let the smaller labs follow up on the promising ones.

"Effort preference" is a weird one. What they say about it in the symposium makes sense - their explanation for what it means and how they never intended it as a psychologizing term. I haven't read the paper so I don't know if what they say now doesn't jive with what was in the paper. But if most of the paper is looking for, and finding, lots of biological abnormalities, would they really still be trying to squeeze in a subtle "it's all in your head"?

And I don't know much about how reasonable their conclusions are - I know the sicktimes blog talks about complaints - but again, I think the main valuable output of this study is loads of data that they are fully releasing to the public on mapMECFS. Anyone is free to analyze the data and put forth better conclusions. I think they said Nancy Klimas is excitedly adding all this data to her existing ME data in her "supercomputer" to hopefully produce new findings.

I'm sure there are actual issues and things that could be done better. But I think people are attributing too much malice and ineptitude to the researchers. My impression from watching them is that most/all of them actually care about the pwME, care to do this in the best way they can, and are motivated to find treatments as soon as possible.

Edit: I do wish they had been able to control for deconditioning, as many or all of these markers could very well turn out to be caused by deconditioning. But if they're limited by resources for sample size, I can see how it'd be an issue to divide the groups down further to healthy and deconditioned controls.
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I'm halfway through Part 3 of Jeannette's blog, and I am much less happy with this study. When Walter Koroshetz said in the symposium something like "effort preference means something different to neurologists; we use it for unconscious moment to moment decisions", I just assumed that was true.

But Jeannette's blog says:

To be very clear, there is no established meaning of the term Effort Preference, and there is certainly no accepted meaning of the term or concept as a defining feature of any disease.

The paper, too, attempts to give the impression of legitimacy of Effort Preference by pretending that it is well established, which it is not:

“[Effort preference] is often seen as a trade-off between the energy needed to do a task versus the reward for having tried to do it successfully.”

“[O]ften seen” by whom? By precisely nobody other than NIH when it comes to ME only.
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Prior Use of the Term
Again, Effort Preference is not an established term. It has been very sparingly used in a few different, inconsistent ways and never as an established term or concept or in connection with a disease, let alone as the defining feature of a disease.

For example, one study used effort-preference terminology to describe the preference to receive effort information before receiving reward information in choosing to complete a task.

Another study used the term in connection with the finding that participants preferred to exert effort for others rather than themselves.
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As mentioned, the label Effort Preference has never been used in connection with any disease. Not even the creators of the EEfRT have used the term Effort Preference, and neither did any of the subsequent EEfRT studies
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I'm just hoping some useful information got through from the other parts, like microbiome and neurotransmitters.

---
Edit: And now having read the second half, I am even more concerned with RECOVER. The implication of not using a 2-day CPET has gotten through to me. They missed an opportunity to validate/probe one of the most promising biomarkers of ME.

The purported rationale for not using a two-day CPET given by Walitt during the Symposium (at 3:59:08) is that the physiological measurements of the CPET (“further collapse of metabolic activity”) do “not measure the experience of [PEM]” but rather cardio-respiratory performance. Moreover, Walitt claims that a second-day CPET was not necessary in light of a brand-new instrument, Qualitative Interviews, that was developed by NIH, for use in the phenotyping study, as the result of a focus-group PEM study. Walitt asserts that the investigators were able to induce PEM with only a one-day CPET allegedly shown by the Qualitative Interviews. Never mind that only eight ME patients participated in the CPET (although the Supplementary Information of the paper, on page 14, inconsistently states that it was nine patients). Finally, Walitt said the researchers did not want to risk harming patients by asking them to do a second CPET.
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Somehow, I am not quite satisfied with their reasons for not using it.
 
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Hutan said:
As much as I support the committee's view that the NIH could usefully be reformed, I found this description of what is wrong with RECOVER rather odd. Epidemiological work, setting up registries and so on - that all seems fine to me. Actually, it was leaping into clinical trials of things like exercise that were a lot more of a problem. Maybe I'm wrong, I haven't been following RECOVER that closely, but that comment, and the RECOVER website too, make it seem like bad clinical trials weren't part of the problem.
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I largely agree with their critique of RECOVER. Of its billion dollars, RECOVER spent 47% of it, roughly $500 million, on an extraordinarily large observational trial with around 40,0000 people. They collected so much epidemiological data - and collected it so badly - that it's all but unusable. Virtually no useful studies have emerged out of that $500 million investment.

Of the original billion, they have spent 13%, around $150 million, on clinical trials, and relative to the results they're getting out of the big observational trial, the clinical trials look very impressive - which is saying something.

This article has a full breakdown of how RECOVER has spent its money so far:

https://www.statnews.com/2024/05/31...-initiative-falls-short-on-causes-treatments/
 
I am as critical of the NIH on a range of issues as anybody. But we do need to be careful about how we criticise them. There are ideological interests in this world unrelated to LC or ME/CFS, or health stuff in general, who want to basically kill the NIH and any government involvement, and they will not hesitate to exploit legitimate grievances about the NIH to further that illegitimate end.

I do not want the NIH to stop working on these medical problems. I do want them to start doing it properly and honestly. They are basically the main game in town when it comes to resources and firepower in medical research. We cannot afford to lose them.

We need to be careful what we wish for. We want them reformed, not removed.
 
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Overhaul threat: NIH faces Republican call for reorganization - Axios
https://www.axios.com/2024/06/17/nih-congress-funding-gain-of-function


Congressional Republicans are calling for a reorganization of the National Institutes of Health that would strip its authority over "gain of function" research and freeze the experiments until new reforms are established.

Why it matters: The draft plan feeds a narrative dating from the pandemic that portrays the government's health agencies as having lost the public's trust and could offer a blueprint for a GOP administration and Congress.

  • It more immediately ratchets up pressureon NIH heading into what could be a difficult fiscal 2025 budget cycle after a long stretch of funding increases was already halted this year.
Driving the news: The plan from the House Energy and Commerce Committee would establish a new oversight process for certain risky pathogen research proposals and transfer power from NIH to a "public, independent oversight entity" to review, approve or reject and oversee the experiments.

  • It would pause such work until "appropriate guardrails to monitor research" are enacted, and would bar NIH from conducting or supporting gain of function research in countries designated as foreign adversaries.
  • It also would incorporate national security or intelligence reviews into the NIH's existing grant approval process, add reporting and conflict-of-interest policies and set five-year term limits for NIH institute directors — a not-too-veiled shot at longtime former NIAID director Anthony Fauci.
What they're saying: "Historical support for what an agency should or could be cannot prevent us from seeking to build upon past lessons or correct areas that have fallen short," Energy and Commerce Chair Cathy McMorris Rodgers (R-Wash.) and senior House appropriator Robert Aderholt (R-Ala.), who oversees Health and Human Services spending, wrote in Stat.

  • HHS, the parent of NIH, says it adheres to strict biosafety measures in its infectious disease research. The Biden administration in May issued an updated policy for research on pathogens with enhanced pandemic potential that expands the scope of federally funded work subject to additional oversight.
The big picture: Even if the reorganization never gets off the ground, it keeps a spotlight on gain of function research, a field that involves boosting the transmissibility of viruses and other pathogens that's often brought up in the context of unproven theories that COVID-19 originated via a lab leak.

  • While such work is touted as a way to understand how viruses evolve and guide pandemic preparedness efforts and the development of treatments, some researchers have voiced concerns about lax oversight of laboratory safety.
  • The Obama administration in 2014 paused 18 research projects involving influenza, MERS and SARS viruses to evaluate risks and benefits, though seven were eventually allowed to continue.
  • There's also lingering debate over whether some studies fall under the rubric of gain of function research, and if swapping natural strains of a virus — as opposed to creating new ones — constitutes "enhancing" a potential pandemic-causing pathogen, per Science.

Reality check: What most can agree on is that NIH has been put on the hot seat by a series of House investigations.

  • A recent report from the committee's GOP staff found NIH misrepresented risky research on mpox — previously known as monkeypox — and denied that the work had been approved when queried by Congress.
  • The House's Select Subcommittee on the Coronavirus earlier disclosed that a top Fauci aide used a personal email address to avoid government oversight and back-channeled with the nonprofit EcoHealth Alliance, whose backing of studies on bat coronaviruses in China put it at the center of the debate over the pandemic's origins.
What we're watching: Lingering partisan acrimony over the pandemic response combined with more recent bipartisan scrutiny of NIH — both on display during Fauci's recent return to Capitol Hill — could make for a rough road ahead for the agency.

  • House Republicans are likely to continue NIH oversight hearings.
  • NIH saw its federal funding decline this year after seven years of increases and could be in for another cut as House Republicans tighten topline figures for health spending.
  • A recent Raymond James report estimated NIH's final FY25 funding could range from $47.9 billion in an optimistic scenario to $44.25 billion in a bearish one.
  • House appropriators are due to begin marking up the main health discretionary spending bill on June 27.
 
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