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

Dakota15 said:
Sharing from Nath (Part 2 below Part 1):

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Transcript from your local fox:
Dr. Avindra Nath: ...here intramurally, and it was not an easy task to put it all together and even write because there were so many different disciplines involved. We've no put it together and the manuscript has been submitted. It's currently under review. So that will have explicit details on everything we did to this population.

However, everything cannot go into a single manuscript, so there are several other manuscripts that are going to come out. Each on of them is going to take a piece of it and describe it in more detail. So a second manuscript on muscle alone is already gone out, is under review, and there will be one on microbiome and so on. So there are going to be a whole host of manuscripts coming out as soon as the first one gets accepted for publication.

We're also keen on trying to see, based on these observations, if we should try to conduct some pilot clinical studies, clinical trials, here at NIH. So those things are currently in the process of discussion. And we've done a lot of work on long Covid over this last three years and we've submitted several manuscripts that were even published, one describing the peripheral neuropathies, one transverse myelitis, two major manuscripts on neurpathology of Covid, one on cognitive aspects of long Covid. This is currently in press.

And we've written lots of reviews, editorals, shared the information with the public with the public and scientific organizations. We've organized workshops on the topic that includes ME/CFS and long Covid. So, tried to get the community engaged the best that we can. We also initiated a study on Gulf War syndrome and those patients have started coming in. And, lastly, we also have a clinical trial for long Covid using IVIG, and so we're currently recruiting patients of that study. So, I'll stop.
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According to Dr. Nath, they have large volumes of research to publish from the ME/CFS intramural study, which is promising. The GWI study is already going which is excellent.
 
A recording and transcript will be posted on the NIH website soon.

A few points I picked up:
The 4 centres they funded a few years ago - Hanson at Cornell has renewed funding, the data center funding will soon be announced and for 2 more centers applications are still open, so presumably the other 2 current centers will be among the applicants.

The main talk was interesting hearing about the next stages of research they are doing and planning, but I think better to wait for the full version rather than trying to decipher my scrappy notes.
 
I did make the webinar. 204 attendees, it will be recorded.

Some notes:
Koroshetz had a conflict and couldn't make the call.

Vicky Whittemore: talking about the trans ME/CFS working group.
Making a Roadmap, to assess what we know and don't know.
Considerable efforts have been made to include people with lived experience in this
There will be webinars from June that the public can participate in.
They will be using a crowdsourcing tool to get input on research programmes
There will be a draft report produced at the end of 2023 which will be presented to the NINDS council in Feb 2024
There's an intention to fund an additional 2 collaborative research centres, as Trish said, in addition to Cornell, so presumably the existing centres will be applying, along with others
A young investigator conference is being planned.

Dr Nath: intramural study and beyond
The transcript of what he said is in a previous post
They are planning clinical trials based on the observations from the intramural study


Joe Green of NIH, part of the ME/CFS working group
Noted two areas of interest
Microbiome - production of butyrate differs in ME/CFS.
This was found by both the Columbia group (Lipkin) and Jackson Lab (Unamatz) - published papers
Highlights pathways where there could be interventions

Post-exercise effects
Cornell published two papers
March 2023, Moore lead author, After exercise testing the healthy controls took 2 days to recover whereas the ME/CFS people took two weeks. Quantitative measurement of PEM may be possible?
Small pilot looking at differences in urine metabolites. This will be followed up.

He encouraged people to visit the Data coordinating centre website, they are adding data all the time

NIH working Group is planning a meeting in December to talk about the status of ME/CFS research. It will be a public meeting with virtual access.
 
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Dr Avik Roy and Dr Gunnar Gottschalk
NINDS has just issued a research award for their work on ATG13 [so perhaps that tells us something about what the intramural study found?]

they collaborate with Dan Peterson at Incline Village and are based at the University of Wisconsin. The lab there at the Milwaukee campus is focused on biomarkers, animal models and drug discovery. There was talk of making use of the drug discovery expertise.

They have two areas of focus:

1.mTOR activation causing autophagy impairment
There was a brief summary of their paper last year that found ATG13 consistently upregulated in people with ME/CFS. It was noted that the ATG13 was phosphorylated, and so, inactive.

There was a nice diagram showing that when MTOR is activated, it causes ATG13 to be phosphorylated, which inactivates it, stopping autophagy. When MTOR is not activated, ATG is not impaired and autophagy proceeds. Activated MTOR also affects other things, e.g. causing STAT3 to become phosphorylated, which affects IL6 and RANTES.

2. translation of this finding into a mouse model

There was a slide with a number of papers listed, with the suggestion that there are contributing factors. These are the papers:
Mitochondrial toxicity - Hansen et all 2016
Upregulations of inflammatory cytokines - Mandarin et al 2020
Myelin abnormality - Morris and Maes 2013
Autophagy impairment - Gottschalk et al 2022
[I wasn't sure what to make of that list.]

For the animal model, they have three strategies
a. drug-induced mouse model for PEM
b. transgenic mouse model, where ATG13 function can be knocked out of specific tissues e.g. muscles, brain, peripheral nervous system
c. virus induced or plasma infused mouse model

They have been working on a mouse model, using something called SIM501. [ I didn't pickup what that was.] After 5 days there were severe impacts on young female mice (it sounded as though older female mice weren't affected). There were some dramatic pictures of activity tracks. Before exercise the controls and SIM501 treated mice moved around their cage a lot. Then all the mice were exercised for 15 mins on a treadmill. All mice moved less the next day. But the SIM501 mice were still not moving the next day. After 14 days, the SIM501 mice had a loss of muscle mass and low growth. Their muscles showed waves consistent with a pattern called 'marching soldier', consistent with inflammatory demyelination. Increasing doses of SIM501 caused decreasing grip strength. There was massive infiltration of inflammatory macrophages into the muscles tissues, macrophages expressing CD40.

But the fatigue effect was transient. After a month, the mice no longer showed the PEM effect. Also the drug is not specific to ATG13, it affects other things too. [Like I said, I missed why they thought this drug might induce PEM. the slides showing differences were dramatic, but it may not have much to do with ME/CFS.]

Avik Roy thinks an MTOR modulator could improve the disease pathology. Rapamycin was mentioned. Some peptides could be designed to prevent disease progression in mice. There was a question about what might be causing the processes that affect ATG13 - Avik Roy said he didn't know.

There was a question about muscle biopsies, Roy said he was interested in those. Vicky Whittemore noted Cornell is currently recruiting patients for a muscle biopsy study. Roy said that he was very interested to see the tissue samples.

There was a question about the demyelination, what could be done to stop the process? [I don't think that we have proof of demyelination - it seemed to be just this mouse model created by injecting a specific drug into them.]. Avik Roy noted that there are drugs available for demyelinating diseases such as MS. He also commented that cinnamon has prevented myelin loss in mouse models - it sounded as though this was work that he had some involvement in.
 
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Dr Nath was asked about the criteria used in the intramural study, the inference being that the MEICC criteria should have been used, and that there is too much focus on the one symptom of PEM. Nath replied that they applied several different criteria and that they were as sure as they could be that the participants had ME/CFS.

He also took a question about if muscle weakness is part of the illness. He commented that ME/CFS isn't muscle weakness, it is exercise intolerance, exhaustion after activity.


My overall impression was of activity and some enthusiasm from NIH for further work in ME/CFS. There also seemed to be a good emphasis on the participation of people with ME/CFS and carers in determining the path forward. Certainly the most positive NIH ME/CFS Working Group webinar that I have heard to date.
 
@Hutan
He (Nath) also took a question about if muscle weakness is part of the illness. He commented that ME/CFS isn't muscle weakness, it is exercise intolerance, exhaustion after activity.
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So very glad to read this. " It (ME/CFS) is exercise intolerance, exhaustion after activity". This is exactly how I experience ME. I have many symptoms but on any occasion when I am more active than I have energy for, I crash. There is never an exception. This gives me hope that it is ME that they have been studying and that something very useful will come out of it.
There have been so many delays that it has been hard to have hope. I think I do now.
I have skimmed today's posts but as a non scientist, I need help in understanding them. Thank you to those who are able to bring them to us with explanation.
 
Shadrach Loom said:
Muscle weakness is a cardinal feature of this illness for lots of us, though, even if it’s bundled in with “fatigue” to fit the criteria.
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Indeed and certainly with time. But there is also the e.g. holding a phone is OK then arm begins shaking as those muscles get tired. As this seems to recover somewhat enough that phone can then be held again at another point in the future it is interesting if this is being studied separately. I couldn't be fully sure, even within 1 person nevermind across people whether one is interacting with the other or what (too much PEM --> downhill --> lower threshold/ muscle weakness issues interacting or something else). But glad that the old 'deconditioning' type hypothesis isn't the starting point given my experience has been the almost exact opposite to deconditioning where good muscle is made worse by keeping going on it.
 
Agreed, @belbyr. Who would've thought NIH & Mayo Clinic would be the ones to at least (finally) help drive some much-needed change (albeit after much patient advocacy).

In 2017, I got diagnosed with ME at the Mayo Clinic and (to me, at least) they hardly believed ME was a biological disease, or a serious one.

In 2023, a Mayo MD is presenting for World ME Day to our local patient community.

Progress can be a crazy thing.


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Moved post

Key House Democrat demands NIH answer for pace of long Covid research
https://www.statnews.com/2023/05/11/eshoo-nih-long-covid/

A powerful Democratic lawmaker is interrogating the National Institutes of Health over its slow progress in addressing long Covid, citing a recent STAT investigation into the agency’s lack of urgency.

Rep. Anna Eshoo, the House Energy and Commerce health subcommittee’s top Democrat, sent a letter to NIH acting Director Lawrence Tabak on Tuesday highlighting the agency’s delays in enrolling clinical trials, the lack of relief for patients, and the exclusion of long Covid from the White House’s Next Gen program to accelerate development of Covid-19 vaccines and treatments. The Energy and Commerce Committee is responsible for overseeing the NIH.

“Congress entrusted NIH with significant funding to provide relief to our constituents suffering from this life-altering disease, but so far, it hasn’t delivered that relief,” Eshoo wrote.

STAT and MuckRock’s investigation found the NIH’s $1.2 billion effort to study long Covid has yielded little useful information for patients, faced delays in starting clinical trials for treatments, generated controversy over the selection of exercise therapy as an area of focus, and is nearly out of money.

Eshoo is also requesting information about the NIH’s remaining budget on long Covid, plans for future spending, specific dates when the RECOVER initiative will start enrolling patients in clinical trials, and how treatments were selected to be tested in clinical trials.

​
 
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Will NIH Wait 40 Years to Try to Solve Long Covid as It Has With ME/CFS?
Billions of dollars spent by NIH with no results and no accountability—who’s to blame? And why are Collaborative Research Centers for ME/CFS only now being created?

In November 2020, Congress allocated $1.5B to NIH to find out why some people with Covid-19 didn’t recover, and to develop treatments for those suffering with Long Covid. Two and one-half years later, there’s almost nothing to show for those billions of dollars, according to an April report in STAT, an award-winning health, science, and public health online journal. (1)

“The National Institutes of Health [NIH] hasn’t signed up a single patient to test any potential treatments—despite a clear mandate from Congress to study them,” Rachel Cohrs and Betsy Ladyzhets reported in STAT. “And the few trials it is planning have already drawn a firestorm of criticism, especially one intervention that experts and advocates say may actually make some patients’ Long Covid symptoms worse.” (1)

Despite disappearing the $1.5B Congress allocated for the Long Covid program, named RECOVER, NIH hasn’t requested more funding to study this syndrome that’s estimated to affect millions of Americans. According to a joint investigation by STAT and nonprofit organization MuckRock, NIH is refusing to use any of its own money to speed up research or change course.

In this investigation, STAT and MuckRock interviewed two dozen government officials, experts, patients, and advocates, as well as examining public documents plus internal NIH correspondence. Nevertheless, it’s hard to tell how this situation evolved, since “the NIH has obscured both who is in charge of the Long Covid efforts and how it spent the money,” according to Cohrs and Ladyzhets.

The Congressional mandate was simple: increase understanding of why some people develop Long Covid while others don’t, and test potential treatments. It’s obvious that no breakthroughs have been made in understanding Long Covid since the study started in February 2021 and, according to STAT, “as of April, RECOVER hasn’t signed up a single patient for any of those clinical trials. And the timeline has slipped over and over again.” (1)

Initially, in a letter to members of Congress prompted by STAT’s March
2022 reporting on the initiative’s slow start, the NIH told lawmakers that
the agency expected to launch clinical trials by that fall. But by August, the
estimated launch had slipped to “by the end of 2022.” Then, another delay
became public in December, when one of the NIH officials leading RECOVER
told advisers that clinical trials would begin by the first quarter of 2023. Now,
Duke University, which is overseeing the clinical trial infrastructure, told STAT
and MuckRock it expects the first patients to sign up for trials this summer
[2023]. (1)

As for following the money, “There is no single NIH official responsible for leading RECOVER, and the initiative has failed to share basic information that would typically be available for a government research project of this scale,” according to Cohrs and Ladyzhets. Instead of directly funding clinical trials, NIH has outsourced them to five research institutions—New York University, Mayo Clinic, Massachusetts General Hospital, Duke University and RTI International (an “independent nonprofit research institute dedicated to improving the human condition”)—and those organizations have funded the trials, not NIH, according to the STAT and MuckRock investigation. Therefore, public databases don’t show how the funding is being spent, and more than one inquiry about it has been rebuffed by government officials. (1)

“The NIH RECOVER study is pointless,” said Jenn Cole, a Long Covid patient in Brooklyn. She tried to enroll but found the process “inaccessible.” It’s “a waste of time and resources,” she told Cohrs and Ladyzhets. (1)

In one of the protocols, NIH planned to test how Long Covid patients respond to exercise. Cohrs and Ladyzhets included a discussion of how damaging exercise is to both ME/CFS and Long Covid patients—so why don’t NIH researchers know about this well-documented phenomenon? (1)

You can probably imagine how this story ends, and the entire report of STAT and MuckRack’s investigation is well worth reading.

Meanwhile, at approximately the same time the NIH-led Long Covid disaster-in-the-making became public, the National Institute of Neurologic Disorders and Stroke (NINDS) announced a “funding opportunity” from NIH titled “Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Collaborative Research Centers (CRCs).” (2)
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Will NIH Wait 40 Years to Try to Solve Long Covid as It Has With ME/CFS? (substack.com)
 
Oh they could wait a lot longer than that.

The pace of science and technology will change this entirely, but I have zero doubt that if technology mostly stagnated overall, leaving medical science at about the stage we are in right now, they could go on failing for 500 years without any progress and find nothing wrong with it.

Fortunately technology progresses so fast that even though medicine is thousands of years old, computer science, not even a century old, will soon create technology that completely outperforms the entire medical profession, even on soft skills. Especially on soft skills. In the end all progress is technology, and it's going too fast to lead nowhere. But the profession has made its choice, and it's the same old: building a pipeline to shovel millions of people straight into the trash. As is tradition.
 
NIH news release dated May 25:

Large study provides scientists with deeper insight into long COVID symptoms

https://www.nih.gov/news-events/new...tists-deeper-insight-into-long-covid-symptoms
www.nih.gov said:
NIH-funded research effort identifies most common symptoms, potential subgroups, and initial symptom-based scoring system – with aim of improving future diagnostics and treatment.

Initial findings from a study of nearly 10,000 Americans, many of whom had COVID-19, have uncovered new details about long COVID, the post-infection set of conditions that can affect nearly every tissue and organ in the body. Clinical symptoms can vary and include fatigue, brain fog, and dizziness, and last for months or years after a person has COVID-19. The research team, funded by the National Institutes of Health, also found that long COVID was more common and severe in study participants infected before the 2021 Omicron variant.

The study, published in JAMA, is coordinated through the NIH’s Researching COVID to Enhance Recovery (RECOVER) initiative, a nationwide effort dedicated to understanding why some people develop long-term symptoms following COVID-19, and most importantly, how to detect, treat, and prevent long COVID. The researchers hope this study is the next step toward potential treatments for long COVID, which affects the health and well-being of millions of Americans.
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Edited to add a link to the thread where this study is being discussed -

https://www.s4me.info/threads/devel...-cov-2-infection-2023-thaweethai-et-al.33487/
 
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