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More people working on these illnesses means more pieces of the puzzle filled in.
We don’t know how chronic fatigue syndrome (ME/CFS), long COVID, fibromyalgia, and allied diseases are going to be beaten, but one thing is pretty clear – it’s going to take a broad-scale effort. It’ll require people, researchers, and organizations working together in ways we haven’t seen before. New people, researchers, and organizations will need to enter the field.
Until we see viable treatments it’s easy to miss the progress that’s being made, more or less, in the background. The good news is that while we don’t know how much money, how many researchers, etc., it will take to get these diseases to a tipping point that produces – as happened with HIV/AIDS – rapid progress in treatments, efforts to expand and treat these diseases are continuing – and sometimes in unlikely places.
This blog is a celebration of a post-infectious field that is slowly but surely expanding,
Whoa! The Schmidt Initiative for Long COVID’s “Multi-Continental” Study
When the Schmidt Initiative says “worldwide: they pretty much mean worldwide.
It’s not often we see multi-continental anything in these diseases, but the newly formed Schmidt Long COVID Initiative is going all in. Its long COVID North and South American and African study is almost certainly the most geographically widespread long-COVID study and maybe the largest as well. When they say “improving clinical care for people with long COVID worldwide they’re not far off. Such is the potential of philanthropy…
The Schmidts have been doing some serious philanthropy for quite a while. Eric Schmidt was clearly in the right place at the right time. The CEO of Google from 2001 to 2011, and executive chairman of Alphabet until 2018, Schmidt was ranked number 30 on the Forbes Top 400 List and number 96 on the World’s Billionaire’s List in 2021. His wife, Wendy, worked in the marketing department of Sun Microsystems and then started an interior design firm, which she ran for 16 years.
Begun in 2006, the Schmidt Family Foundation supported numerous environmental causes over time but in 2023, shifted gears and started the Schmidt Long COVID Initiative. The Initiative’s main goal is finding treatments for long-COVID treatments NOW.
It’s moving at lightning speed – one of the great advantages of philanthropic giving. The first part of the study, which originated from Western University in Canada contained 6,000 participants and is already finished. The study used advanced bioinformatics and machine learning to identify 13 signaling pathways linked to long-COVID symptoms such as fatigue, brain fog, and muscle pain. (Note that it’s likely that similar signaling pathways will be dysregulated in ME/CFS as well.)
The researchers then searched every FDA-approved drug to find repurposed drugs that could impact those dysregulated signaling pathways. That search was successful. The leader of the effort, Dr. Douglas Fraser, explained, “By leveraging drugs that are already FDA-approved, we can save years of development time and billions of dollars.”
This isn’t Fraser’s first go-around with long COVID. He’s published five long-COVID studies, the latest of which targeted vascular inflammation as a key driver in the disease.
He’s about ready to move on with clinical trials involving 1,200 participants slated to begin in early 2025. We don’t know what drugs or how many they came up with, but given how fast they’ve been moving, it may not be long before we hear about some drugs – perhaps ones we’ve never considered – that will work in long COVID.
Rapamycin Relief on the Way?
Simmaron has expanded its Rapamycin trial
Speaking of potential drugs… Rapamycin, with its ability to reset the mitochondria and improve autophagy (and its longevity component), presents a fascinating drug opportunity.
Rapamycin I
After Health Rising posted a Rapamycin recovery story, Simmaron’s mouse model suggested Rapamycin was worth a shot, and Simmaron quickly – note the quickly – began an ME/CFS and long-COVID clinical trial.
After noting that he’d seen patients benefit in the past, David Kaufman, the lead clinician in the trial, stated:
“The beauty of this trial has been, by virtue of it being decentralized and internet/RedCap based, that we have been able to rapidly recruit patients and acquire data that may confirm our hypothesis using biochemical biomarkers and validated survey tools”.
Simmaron’s approach presents the possibility of cheaper, faster, and more numerous clinical trials. It recently announced that it formed a strategic partnership with AgelessRx, a leader in decentralized clinical trial execution. Simmaron is expanding the ME/CFS Rapamycin trial and looking forward to future trials with AgelessRx.
“We’re paving the way for future studies using FDA-approved agents such as GLP-1 agonists, metformin, and innovative combination therapies.”
Rapamycin II
Just a month and a half ago, PolyBio announced that it was funding an $800,000 long-COVID rapamycin trial at David Putrino’s new CoRE clinic. Thankfully, both trials are digging into the participants’ physiology to understand: a) which patients respond to the drug; and b) what Rapamycin is doing to them.
Nice Diversification of Efforts – Simmaron is developing an Elisa-based assay to assess mTOR-driven mitochondrial autophagy disruption they hope will help them identify which ME/CFS patients might respond to the drug. Putrino’s PolyBio study, on the other hand, will be digging deep into their immune and hormonal systems to see what’s happening there. Amy Proal noted that rapamycin is increasingly being used to enhance immune functioning, including the production of a key component of our antiviral defenses – interferons. Interestingly, none of the participants in a COVID-19 rapamycin trial came down with long COVID. Plus, low-dose rapamycin may be able to help with T-cell exhaustion – a problem found in both long COVID and ME/CFS.
Dr. Putrino, the clinical lead, stated, “We are hopeful that this will be a first step in validating a cheap, safe and effective long COVID treatment.”
CoRE Post-Infectious Disease Clinical Center Opens up at Mt Sinai
CoRE’s autonomic testing area
The Gist
- Until we see viable treatments it’s easy to miss the progress that’s being made, more or less, in the background. The good news is that new efforts to expand and treat these diseases are happening – and sometimes in unlikely places. This blog is a celebration of a post-infectious field that is slowly but surely expanding.
- The Schmidt Initiative for Long COVID’s “Multi-Continental” Study, for instance, has moved with lightning speed to produce a 6000-person study across North and South America and Africa that it uncovered signaling pathways it believes it can treat, and is about to begin a 1,200-person clinical trial using repurposed; i.e. already available drugs.
- The initiative is moving so quickly that it might not be long before we have study evidence of a number of drugs that might help in long COVID.
- Speaking of treatment possibilities, two Rapamycin clinical trials are underway in ME/CFS and long COVID- one funded by the Simmaron Research Foundation and one by PolyBio. Both are digging into the participant’s pathophysiology to learn who benefits from this drug and what effect it is having on the immune system.
- A ten million dollar post-infectious disease clinical center called the the Cohen Center for Recovery From Complex Chronic Illnesses (CoRE) Opens up at Mt Sinai. This beautiful facility will not only bring the latest treatment options to these disease but will study post-infectious diseases like ME/CFS, long COVID, post-treatement Lyme disease and others side by side.
- PolyBIo’s million dollar grant to UCSF’s LIINC long COVID project allows ME/CFS get linked up with long COVID. Included in the grant is first ever study to rigorously validate and expand on Dr. Chia’s enterovirus results and a whole body scan to determine where in the spine and the brain T-cells are activating and producing damage.
- In what is potentially a “monumental step forward” efforts thus far have succeeded in getting Congress to include ME/CFS in the NIH’s Long COVID RECOVER project. With RECOVER revamping its clinical trials approach to be more nimble and creative, having ME/CFS alongside long COVID in the project could reap dividends.
- The German government is plowing $16 Million into translational ME/CFS research designed to produce treatments as Germany becomes ever more a major player in the ME/CFS field. It’s a remarkable change for a country which 10 years or so ago, was an afterthought in the field.
- Similarly the Dutch have launched a ten year program one of whose studies hopes to do for ME/CFS what it did for autoimmune diseases – quickly provide diagnostic criteria and treatment options for its doctors. The research group anticipated that “treatments might be made available quite quickly“.
- PolyBio has funded the first long COVID TISSUE bank that will include gut, lymph, cerebrospinal fluid and bone marrow samples. The bank will allow LIINC researchers to search for the viral reservoir they believe is driving the disease.
- Increased collaboration and a search for treatments are two key themes. The ME/CFS and long COVID fields are continuing to expand and intertwine as they focus on finding treatments as soon as possible for these diseases.
Once again, philanthropists were at the fore of this. This philanthropy stuff is important. Former Solve M.E. President Carol Head noted how difficult it was to get philanthropists to help out ME/CFS. Vinod Khosla has helped to fill in the gap recently with ME/CFS, but long COVID has fared better.
An inaugural gift from Beth and Joshua Nash and a naming gift from the Steven & Alexandra Cohen Foundation topped off a wide range of philanthropic contributions, including the PolyBio Foundation, to create the Cohen Center for Recovery From Complex Chronic Illnesses (CoRE).
Amy Proal of PolyBio and David Putrino, the leader of CoRE worked on the clinical trial designs
Patients will get the most up-to-date treatments (everything from virtual reality to HIV drugs to supplements) in an environmentally safe area (including a special air filtering system) but where the new Center really shines, in my opinion, in its research efforts to compare and contrast long COVID, long Lyme disease/Lyme+, ME/CFS, EDS, and other infection-associated complex chronic illnesses. The new Center will focus on
- Metabolic and hormonal regulation
- Immune function and viral activity
- Vascular and endothelial function
- Autonomic nervous system health
- Cognitive function
- Tick-borne and vector-borne pathogen screening
This is the second time in about a year – the first was Metrodora – that a major effort to treat and study these diseases opened in the U.S. – a good sign. Note that each was powered by philanthropic efforts – another good sign.
LIINCING UP with ME/CFS
“Our research is designed to identify therapeutic targets that might become the basis of experimental medicine studies in ME/CFS.” Dr. Michael Peluso
PolyBio has been mostly focused on long COVID, but with Amy Proal and Michael VanElzakker at its helm, it has deep ME/CFS roots as well. Amongst its dozens of long COVID projects are 5 ME/CFS ones. Its most recent project – to get ME/CFS patients embedded into the long COVID LIINC effort at UCSF – is welcome indeed.
The $1 million donation will do several things. For one, it will allow ME/CFS infectious, immune, and genetic analyses to be contrasted with long-COVID ones.
John Chia’s work will finally get the attention its deserved
The Hunt Continues – For two – it will make John Chia MD happy :). Enteroviruses were the first viruses researchers – back in the 1950s – thought were causing myalgic encephalomyelitis. Pouring out study after enterovirus study from his small practice, Chia showed remarkable persistence but never got near the support he needed and deserved. Indeed, aside from one small effort at the CDC, I can’t remember a single attempt to replicate his findings – an astonishing lapse for a research effort that captured a lot of attention (but little funding).
Now enteroviruses are getting quite the second look. With their deep experience hunting for HIV and other viruses, LIINC researchers will be using cutting-edge technology to look for enteroviruses and other pathogens in ME/CFS gut tissues.
With PolyBio’s help and LIINC’s expertise, we may finally have an answer for the 70-year enterovirus question.
The Brain and Spine T-cell Study – T-cells and T-cell exhaustion has become a big enough deal in ME/CFS that the NIH awarded one of its rare major grants (RO1) to study T-cells. LIINC will go a step further and do full-body imaging to see where in the brain and spinal cord and these powerful immune cells are being activated – and presumably doing damage.
We’ve known from the beginning of the pandemic that if there’s one thing the ME/CFS field needs to do, it’s get embedded into long-COVID research efforts. The more we know about the similarities and differences between these two diseases, the better chance ME/CFS has with its limited funding, of piggybacking on the breakthroughs in long COVID that are sure to come.
The Long COVID ME/CFS RECOVER Initiative?
On that note, some good preliminary news from #NOTJUSTFATIGUE indicates that the Senate Appropriations Committee has included language in its 2025 (FY25) appropriations report (pg. 145-146) directing the NIH to incorporate ME/CFS into the RECOVER Initiative. Elizabeth Ansell, the founder of #NotJustFatigue, called this potentially a “monumental step forward” and is hopeful that the new directive will remain intact through the final budgeting process.
This could be a very big deal. While RECOVER has decidedly underwhelmed thus far, it appears to be dramatically revamping its clinical trials effort to make it more creative, nimble and effective. We should be seeing platform trials, small trials that explore long COVID pathophysiology, and more high-risk, high-gain trials. With RECOVER having an extra $500 million to burn, we REALLY want ME/CFS in RECOVER.
With all the criticism directed at it – one would expect its research effort will get the same treatment. Big initiatives often fail in the beginning only to straighten out later on.
One last note: the National Institute of Neurological Disorders and Stroke (NINDS) is about to publish what appears to be its – and the NIH’s – first stand-alone grant packages not for long COVID or ME/CFS but for post-infectious diseases. The NIH may be slowly catching up.
German Government Plows $16 Million into ME/CFS Research
“Germany has the best prerequisites to become one of the world’s leading research locations for ME/CFS and post-infectious diseases.” Prof. Carmen Scheibenbogen,
The German govt is plowing money into a search for the mechanisms driving ME/CFS
Perhaps more important than the money pledged (@$5 million/year) is the fact that ME/CFS research continues to expand in what was essentially a no-man’s land for ME/CFS for decades. Until about ten years ago when Carmen Scheibenbogen showed up, I don’t remember a single ME/CFS paper coming out of Germany. Now Scheibenbogen believes Germany has the potential to become “one of the world’s leading research locations for ME/CFS”.
The German ME/CFS Research Foundation called the grants “an important milestone” and noted that the funding will explore genetic, cellular, and molecular pathomechanisms, will engage in modeling and identifying “new predictive, diagnostic or prognostic biomarkers, seek to identify subsets, and identify treatment targets.
The ME/CFS Research Foundation will be piggybacking on these studies to fill them out with complementary research. A hopeful Carmen Scheibenbogen noted the “translational” (i.e. treatment-oriented) nature of the projects.
“Most research projects within the new BMBF funding programme are very translational in their approach, in order to gain insights to improve diagnostics and develop targeted treatments” Prof. Carmen Scheibenbogen
The new funding comes on top of the @$10 million funding from 2022-2023; and $2.3 million for the 2022-25 immune mechanisms study. While more is needed, in a relatively short period, the German government is now funding about half as much ME/CFS research as the $48 billion NIH in the U.S. is.
The Dutch Turnaround
The next venture comes from another unlikely source – the Netherlands. In contrast to Germany, the Netherlands has a long history of funding ME/CFS research; err… CBT/GET studies. Things have changed, though – and it all began with a petition in 2013 that Groep ME-DenHaag submitted, called ‘Erken ME’ (‘Recognise ME’) to the Dutch parliament.
If everything works the way it did with autoimmune diseases, “treatments might be made available quite quickly”.
Skip forward to 2021 when ZonMw – the medical research arm of the Dutch government – launched a ten-year research ME/CFS program involving ten studies. The project involves housebound and bedridden patients, incorporates people with post-COVID and Lyme disease, and will be using blood samples from the ME/CFS biobank of the Netherlands’ ME/CFS Cohort and Biobank consortium.
The immune effort promises to create the same “easy-to-use blood tests” that they developed for some autoimmune diseases for doctors. They anticipate that some of the same immune signatures will be found in ME/CFS, and if they are, the group anticipated that “treatments might be made available quite quickly“.
ZonMw is also funding Rob Wust, whose muscle studies have already made a big splash. Wust will be using muscle biopsies and blood samples taken before and after an exercise challenge to assess what exercise does to muscle functioning, blood clots, and immune functioning.
If the Dutch can turn around, anyone can turn around. Which European country is going to step up next?
The First Tissue Bank for Long COVID
It’s hardly a surprise that the University of California at San Francisco (UCSF) based LIINC project would be the first – thanks to a $3 million grant from PolyBio – to open a tissue bank for long COVID. The UCSF-based group has been on the cutting edge of long-COVID research since the very beginning.
Why a tissue bank instead of just a blood bank? Because, Micheal Peluso, the chief investigator of the program, believes the tissues – and the viruses and bits of virus that are in them – may hold the key to long COVID. He stated:
“Based on our work so far, we believe that long COVID is a tissue-based disease”
The role that pathogen-infected tissues play in ME/CFS and fibromyalgia has been a major question for decades: the fields just haven’t had the resources to explore them. Both John Chia and Skip Pridgen found pathogens in the gut tissues of ME/CFS and fibromyalgia patients, respectively, and fibromyalgia muscle tissue studies have been illuminating, but they’ve never received a full-court press.
Times are changing. Rob Wust’s muscle tissue study produced dramatic findings and the Open Medicine Foundation is digging deep into the muscles of ME/CFS and long-COVID patients in its studies. Plus, let’s celebrate a newly funded ME/CFS muscle tissue study from an unlikely source – the NIH.
Now LIINC, in its search for viral reservoirs, will dive not in the muscles but into the gut tissues, the lymph nodes, spinal fluid, and bone marrow. Instead of a duplication of efforts, we now have a nice diversity of efforts looking at different tissues in the same diseases.
(But what, might you ask, about the RECOVER Initiative’s $30 million Mayo Clinic long-COVID biorepository? Who knows? Neither RECOVER nor the Mayo Clinic has, to my knowledge, said exactly what’s in it. Time will tell, but with RECOVER’s simplistic efforts to characterize long COVID, it’s hard to imagine that it’s taking lymph, gut, bone marrow, or even spinal fluid samples.)
Conclusion – An Intense Search For Treatments
Increased collaboration and a search for treatments are two key themes. Check it out: we have a huge multi-continental study looking for repurposed drugs, a Dutch initiative that believes treatments could be available quite quickly, a large post-infectious, multiple disease clinical / research center opens, two Rapamycin trials – one each in ME/CFS and long COVID are underway, ME/CFS joins with long COVID at the LIINC project and possibly the RECOVER Initiative, a reinvigorated RECOVER clinical trials effort shows promise…These fields are moving in the right direction.
Health Rising’s Donation Drive Update!
Things are moving and the arc is indeed upwards.
Thanks to the over 150 people who have donated to Health Rising’s Donation Drive.
It’s easy to miss things and get lost in the weeds as we face our day-to-day challenges. As this blog hopefully shows, though, the arc in the post-infectious disease space is upwards and the focus on finding treatments sooner rather than later is gratifying.
As difficult as these diseases are it’s no time to be resigned or give up hope. If this blog supports you please support us!
My understanding is that the Dutch are looking at some interesting potential treatments for mitochondrial dysfunction in long covid and ME/CFS
Who would have ever thought even five years ago that anyone would say that? It’s kind of amazing – and a very good sign.
Cort – do you see any of these efforts including fibromyalgia patients or directly benefiting fibromyalgia through findings? Thanks
Not anything on fibromyalgia in the blog! (I looked!). Honestly, I see literally everything potentially benefitting fibromyalgia. While it’s more on the pain spectrum it’s just too close in too many ways not just with regard to symptoms but biologically to ME/CFS and long COVID for FM not to benefit. Do you remember what Avindra Nath said regarding these diseases: “If you solve one you will probably solve them all”. I believe that’s true.
Nath’s comment is nothing more than a belief. As you say yourself, you believe that too. It’s like saying: if you know the cause of a cancer, you can cure all cancers. We know that several causes can cause this disease, the same applies to ME. It is also noted what you use as definition and criteria.
🙂 – If you know the cause of a cancer, you can cure all cancers – the thing is there are cancer of the blood, cancers of the bones, cancers of the skin, cancers of the brain, cancers of the breast – and on and on and they are all VERY different.
From what we can tell now – the autonomic nervous system, blood vessel, metabolic, gut, muscle, mitchondrial, and brain findings – are all pretty similar in ME/CFS, long COVID and fibromyalgia. That’s why I believe he’s right – the biological findings are just too close. If they weren’t I would think differently but I’m honestly shocked at how close they are.
Hopeful news, thanks Cort! Do you know what dosages of Rapamycin are being trialled?
I was in the Simmaron trial – it started at 1mg taken once a week and increased to a once a week dose of 6mg. I was unable to complete the trial due to an unusual side effect. I had severe pain in my left side and we couldn’t figure out what was causing it, but I had to drop out.
Rather than watch from the sidelines as treatments are developed, the alternative approach that I’ve adopted is to look at the likely source of symptoms.
While other root causes may exist, mounting evidence points to secondary mitochondrial dysfunction.
My strategy has been to focus on mitochondrial vitality. Details can be found on my Substack posts. A summary can be found here: https://longcovidjourney2wellness.substack.com/p/long-covid-tlc-for-mitochondria
A more in-depth post, Tackling Mitochondrial Dysfunction, https://longcovidjourney2wellness.substack.com/p/tackling-mitochondrial-dysfunction
goes into greater detail. This post includes more information on nutrients and diet.
These posts are open to all readers.
Thanks Cort, for deftly writing a summary of German sources for me to digest 🙂
Here is the link listing the abovementioned German research projects, where Scheibenbogen’s quote is from (which is not yet linked in this blog): https://mecfs-research.org/en/bmbf-researchfunding-nov24/
It also includes an interesting detail: The last project on the list ” FAME – Functional autoantibodies against G-protein-coupled receptors in patients with ME/CFS (external link) Total funding: 1.759.607 €, Principal investigator: Dr Bettina Hohberger, University Clinic Erlangen” means that Dr. Hohberger at eye clinic Erlangen, who was involved with the first BC007 treatments, seems to continue to delve into ME/CFS research independently of BC007, trying to learn more about a potential role of functionally active GPCR antibodies in ME/CFS. Even though BC007 clinical trial failed, Scheibenbogen said in another interview that this doesn’t mean these antibodies couldn’t play a role in ME/CFS as “we don’t know if BC007 can neutralize them”. It’s interesting to see how people like Dr. Hohberger who come from totally different fields now delve into ME/CFS.
Being German, I had the chance to watch several presentations from Dr. Hohberger over the last years (unfortunately, all of them are in German language only).
She and her team (and basically the whole University of Erlangen) are much more into the demistification of Long Covid as people would expect.
They have not inly discovered the link between BC007 and Long Covid, they also have started to identify possible pathways and diagnostic options (she actually reported once that they are closely working together with machine learning specialists and have already found a diagnostics mechanism that is correct in about 95% of the cases)
Moreover, a week ago, she publicly stated that despite the fail of the BC007 study, they have made other observations regarding their own (independent) BC007 research. Based on her statement, it is extremely important to select the correct Sub-Group of patients (and apparently, they are capable of doing so).
Long story short: I expect some very important progress for the whole LC research community coming from Dr. Hohberger within the next 12 months.
By the way: BC007 will not entirely disappear. The company went bankrupt, but ist was only a sub-company of the actual Parent Group. They are still working on the BC007 product for its initial purpose (heart), so it would be still there for further trials and potential off-label use.
Thanks so much for letting us know, Oliver. This brings up an important point- we should NEVER dismiss a treatment because it doesn’t work for the group as a whole. I believe it may have been Florinef that failed in a clinical trial but which doctors, then and now, find very helpful for the right kind of patient.
Looking forward to hearing more from Dr. Hohberger over the next year or so.
And how about Germany! It’s amazing how quickly its grown into a major center of ME/CFS research….
“It’s interesting to see how people like Dr. Hohberger who come from totally different fields now delve into ME/CFS.” – exactly what we want…
I got a giggle from your reference to Western University in Canada, the name implying that it is somewhere in western Canada. In fact it is in eastern Canada, slightly west of Toronto, the centre of the Canadian universe. Sorry, had to laugh out loud. But your blog post is very hopeful, I like that multi-billionaire philanthropists are getting on the bandwagon. Could it be that they have family members affected by these dreadful diseases?
I didn’t know that! I’ve heard though that Torontonians think Canada kind of ends at the city limits – so something located on the western side of Toronto ends up being called “Western University” (lol).
I did read that one of the Schmidt’s daughters died of a chronic illness a couple of years ago but I could not tell what it was… so it’s possible.