ME/CFS and FM Moments?
Taking it to the next level for ME/CFS and FM?
I think of “moments” as unusual events that suggest the tide may be turning for these common but sorely neglected diseases.
Health Rising has documented several possible ME/CFS “moments” over the past two years and now we have one for fibromyalgia.
The first ME/CFS moment was a big win for Ron Davis – one of the greatest grant recipients in all of medicine – that is, until he tried to get them for ME/CFS – and ran into roadblock after roadblock. One wonders if Davis’s big 2022 win indicates that grant funders are taking ME/CFS more seriously. On that note, the Congressionally Directed Medical Research Program ME/CFS recently put ME/CFS grants into the priority column – another possible “ME/CFS moment”.
In May of 2022, Health Rising reported that both Bateman Horne Center and Benjamin Natelson were up to their ears with work. After a dry spell, Natelson was suddenly scoring grant after grant and the BHC was up to its neck in clinical trials.
Next, came probably the most astonishing moment yet. Perhaps the most single most backward and despised medical group in the entire country – the Mayo Clinic – apparently had something of a come-to-Jesus moment – and actually asked MEAction to help them develop a better ME/CFS treatment program. That was surely a sign that things were changing.
We could slide the integration of ME/CFS into the CDC-funded ECHO program on treating long COVID into the ME/CFS moment category. That, after all, resulted in physicians across the country learning about both long COVID and other fatiguing illnesses (like ME/CFS). Getting the CARE for LONG COVID bill – which includes ME/CFS in it – would certainly constitute an ME/CFS moment as it would speed about $100 million into better education for doctors, treatment assessments, and patient registries for both diseases. Ditto with the strategic plan for ME/CFS that’s underway at the NIH. If that goes over well and ends up with better funding for ME/CFS – that would certainly qualify as an ME/CFS moment. We may be having ME/CFS moments coming out of our ears at some point…
Hanson ME/CFS Research Group Grant
First comes the big grant that the Hanson ME/CFS research Center for Enervating Neuroimmune Disease at Cornell just scored – a nice, large $9.5 million grant over five years.
One thing that made this grant so special was where it came from – one of the three NIH-funded ME/CFS research centers. This grant is further evidence that these centers work (and should be expanded). They’ve shown that given sufficient funds, ME/CFS researchers can produce meaningful results and that ME/CFS is not an impenetrable disease.
Considered by some to be a wastebasket disease not worth studying, these big, high-powered NIH-funded studies are proving that idea a lie. As Andrew Grimson, one of the Cornell researchers, said – they took a broad approach – and lo and behold, specific molecular targets popped out.
“We took a broad interdisciplinary approach, with the hope that we would find specific molecular changes in ME/CFS; now that we have found these changes, we can target our research on these changes and understand their impact, ultimately moving towards a cure,”
The grant will focus on three aspects.
Monocytes – Grimson’s NIH-funded study was eye-opening, indeed. Using a fine-tuned gene expression approach new to ME/CFS, Grimson’s results potentially turned our understanding of ME/CFS patients’ immunology on its head.
None of the usual suspects – the NK cells, T- or B-cells – popped out, instead it was monocytes – a cell we’ve hardly ever heard of in connection with ME/CFS. The amazing thing was how strongly they showed up – they were clearly leading the show – and that’s good news. Strong findings like that provide clarity – a clear angle of attack. Given all the disparate immune findings in ME/CFS, having one cell show up big time like that was good news indeed.
Muscle Biopsy – Next, a deep, deep, deep dive into the muscles. Anyone who’s had ME/CFS would be shocked, I would bet, if the muscles weren’t involved in a major way – yet they’ve never been examined as deeply as they should be. ME/CFS muscle research is a glaring need.
In this project, Ben Cosgrove, and Iwijn De Vlaminck, will use a new machine to take detailed gene expression analyses in different parts of the muscle tissue that could potentially locate the exact cells where things have gone haywire. They’ll also look at the gene expression in muscle fibers, blood vessels, and immune cells.
Exercise Study – You would have thought ,given all the fascinating exercise results from Hanson’s NIH-funded ME/CFS research studies, that an exercise study had to be in here somewhere – and it is.
Among other things, those studies found dramatic reductions in the production of metabolites and proteins in ME/CFS patients vs healthy controls. This study will analyze RNA released into blood plasma when cells die, before and after exercise, as people with ME/CFS respond abnormally – and adversely – to exercise. This study will further the protein work and further assess the effect of exercise on gene expression. They will also analyze the extracellular vesicles from platelets, neuronal cells, and blood vessel cells.
Update! – I got this wrong. Because the grant announcement never mentioned the NIH ME/CFS Centers I assumed this was a separate grant. It was not – this is the Centers grant and as such, while it is an excellent grant, it was expected – and thus does not constitute an ME/CFS moment. 🙁
Fibromyalgia’s Moment
Further research is needed, but this offers hope to the millions of people with fibromyalgia that an effective treatment could be found in the relatively near future – Dr. Craig Bullock, Research Discovery and Innovations Lead at Versus Arthritis.
Fibromyalgia is potentially in the midst of its own paradigm-changing moment. It all started with Andersson and Goebel’s 2021 stunning study, “Passive transfer of fibromyalgia symptoms from patients to mice“, which found that giving mice IgG antibodies basically gave them fibromyalgia – suggesting that fibromyalgia is an autoimmune disease. The consistency of the findings even surprised the researchers on the team. Andreas Goebel said:
“When I initiated this study in the UK, I expected that some fibromyalgia cases may be autoimmune. But David’s team have discovered pain-causing antibodies in each recruited patient. The results offer amazing hope that the invisible, devastating symptoms of fibromyalgia will become treatable.”
That was just the beginning. Fibromyalgia has primarily been thought to be a central nervous system disease, but when the researchers looked deeper, they couldn’t find any evidence that antibodies had made their way to the central nervous system. Instead, they were concentrated and presumably attacking the major sensory processing center outside the spinal cord – the dorsal root ganglia. Suddenly, fibromyalgia was looking more like a disease of the periphery than a disease of the central nervous system. The fact that the study involved two separate FM groups – one from the UK and one from Sweden – further buttressed its findings.
The Gist
- “Moments” are signs that a disease may be turning a corner. We’ve documented several possible ME/CFS moments – Ron Davis’s big grant, a high workload for the Bateman Horne Center, Ben Natelson’s string of grants after a dry spell, the Mayo Clinic coming to MEAction to help them treat ME/CFS patients better.
- Now comes two possible moments – one for ME/CFS and one for fibromyalgia.
- The ME/CFS moment involves an immense grant that Maureen Hanson and her ME/CFS research got. It’s significant because it’s so large and because it grew out of NIH-funded ME/CFS research center work, and thus demonstrates how effective these research centers can be (and why we need more of them).
- The grant will have three thrusts. One will follow up on the potentially ground-changing finding that it’s monocytes – not NK cells, T or B-cells – that are at the heart of the immune dysfunction in ME/CFS.
- Another will use new technology to uncover – on a cellular basis – where the muscles have been impacted in ME/CFS. The third will assess the effects of exercise on gene expression.
- The FM “moment” involves another potentially paradigm-changing study that could potentially turn the world of FM research and treatment on its head. This study will probe more deeply into the possibility that FM is an autoimmune disease caused by antibodies attacking the central sensory processing center (the dorsal root ganglia) leading to the spinal cord. A successful outcome would open up a wide range of treatment options never thought before to apply to FM.
Next, they convened a group of 29 stakeholders (including 3 patients/caregivers) and produced a research strategy for fibromyalgia. Dozens of research projects were assessed. Of the top five recommendations, three involved antibodies.
Then in October 2022, Andersson and Goebel (and Schofield) argued in, “The biology of symptom-based disorders – time to act“, that “symptom-based disorders are… very common, including pain and fatigue disorders, functional gastrointestinal and respiratory disorders” and “cause far greater disability than diseases where signs are prominent.” They urged funders to pour “resources into exploring the role of ‘invisible’, functional, non-inflammatory autoantibodies in symptom-based disorders”.
Andersson hit pay dirt this month when he won the Sir Jules Thorn Award for Biomedical Research, giving him and his co-investigators (including Goebel) £1,699,572 ($2,100,000) over five years.
Stating that, “These insights will fundamentally change future research and clinical management of FMS“, the award was very clear on the tremendous possibilities present. In an attempt to find a treatment target and biomarker, Andersson et al. will identify which molecules the patients’ autoantibodies are binding to (i.e. attacking). He will also dig deeper into what’s going on with the neurons that relay sensory information to the central nervous system and see how all this affects the central nervous system.
Time will tell if these are moments or not. Are the Ron Davis and Maureen Hanson awards harbingers of more funding? (Will Ian Lipkin and his peroxisomes get the next big grant?) Will the FM award end up reshaping how we think of fibromyalgia and open new treatment possibilities? Time will tell.
Hope something out of this bunch can help those of us who have been sick for decades; thanks for the detailed recap – and your attention all these years.
Cort, you have never ceased to amaze me. I am so very grateful to know you. We live teetering on the edge of total despair, but holding on to a glimmer of hope during these times. I believe the pressure from our community is helping. I am so thankful for the ME CFS trailblazers, and I pray the suffering from ME CFS will be extinguished and the same will hold true for Fibromyalgia and Long Covid sufferers. Yes, the time is now, right now, even better.
Hope is all we have. I have great interest in the upcoming publications from Professor Nath and Dr. Prusty. I expect that a biomarker will emerge from 1 of these studies. But we’ve been disappointed for more than once in the past. But it’s good to read that more research is on the way.
Prusty seems very excited! Let’s hope that time shows that his excitement was justified and that he can garner the resources needed to turn it into something that benefits all of us.
I, too look forward to Nath’s paper with anticipation and a bit of dread actually – will it have powerful findings that help to propel this field forward and set us up for more big NIH grants? Time will tell….
yes, Prusty is verry convinced of his biomarker finding. II really hope he is correct with it. even a piece, a start would be great.
thanks again for the hope Cort! I really hope that they awake worldwide with tons of research!! biomarkers and treatments…
Thanks! Time will tell if the arc bends strongly enough to help those of who are getting on in years! 🙂
The approved therapy for fibromyalgia is not effective and has no effect on most people. They are about 10% stronger than placebo, which means they only have an effect on about 10% of the population.
My feeling is that due to the heterogeneity of FM, it is basically certain that some patients have immune factors, and the proportion may not be small.
It was so good to see Andresson get this big grant. This is a once a year grant and it’s not just for fibromyalgia. I’m sure the competition was rough. It certainly is a potential gamechanger for FM.
Thank you Cort! I would know considerly less without your blog. Science is beautiful!
Thanks for sharing the Fibromyalgia new,s as I am not up to date on that front. I read somewhere that some of the Hanson grant money has to go towards cancer research, is that true?
I can’t imagine why anyone would say that. Grant funds are strictly proscribed. The study is not yet up on the NIH’s project reporter site but should be soon
https://reporter.nih.gov/search/kkV_KHuqW0WTD38HPOu51Q/projects
Thanks a lot for clarifying. Seems like I had mixed up things quite a bit and it is the NIH that appears to be counting a $3.6 million study of cancer-related fatigue as part of its $13 million 2022 portfolio of ME/CFS spending which David Tuller seems to have exposed.
No kidding. I’ve got to check that out…
Thanks for the info. 🙂
oh no!!!
Thx so much Cort. Ever bit of progress and hope is precious. My fibro has gotten much worse since having covid.
I hope they find the link between the two soon and can offer new treatments.
It’s lonely having a mysterious illness and knowing more about developments than the doctors I see.
Thank heavens for the support and wisdom of your blog and this group.
I am so grateful.
I am a 26 year Fibromyalgia sufferer, a MSN/Researcher with pharmas. Also had Covid. Have seen little progress in treatment over this many years. But have had a number of gifted physicians willing to step outside the box. I pray this a really positive move forward in discovery and cure of this life altering disease.
Another wonderful story filled with hope! Thank you!
Here is a related article:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787228/
Dorsal Root Ganglia: fibromyalgia pain factory?
This perspective article focuses on dorsal root ganglia (DRG) as potential fibromyalgia main pain source. Humans possess 31 pairs of DRG lying along the spine. These ganglia have unique anatomical and physiological features. During development, DRG are extruded from the central nervous system and from the blood-brain barrier but remain surrounded by meningeal layers and by cerebrospinal fluid.
DRG house the pain-transmitting small nerve fiber nuclei; each individual nucleus is tightly enveloped by metabolically active glial cells.DRG possess multiple inflammatory/pro-nociceptive molecules including ion channels, neuropeptides, lymphocytes, and macrophages. DRG neurons have pseudo-unipolar structure making them able to generate pain signals; additionally, they can sequester antigen-specific antibodies thus inducing immune-mediated hyperalgesia.
In rodents, diverse physical and/or environmental stressors induce DRG phenotypic changes and hyperalgesia. Unfolding clinical evidence links DRG pathology to fibromyalgia and similar syndromes.
Severe fibromyalgia is associated to particular DRG ion channel genotype. Myalgic encephalomyelitis patients with comorbid fibromyalgia have exercise-induced DRG pro-nociceptive molecules gene overexpression. Skin biopsy demonstrates small nerve fiber pathology in approximately half of fibromyalgia patients.
A confocal microscopy study of fibromyalgia patients disclosed strong correlation between corneal denervation and small fiber neuropathy symptom burden. DRG may be fibromyalgia neural hub where different stressors can be transformed in neuropathic pain. Novel neuroimaging technology and postmortem inquest may better define DRG involvement in fibromyalgia and similar maladies. DRG pro-nociceptive molecules are attractive fibromyalgia therapeutic targets.
I’ve had FM for over thirty years. When I awaken in the morning, I am generally stiff at the base of my back in the vicinity of the DRG. I sometimes also have pain in my shoulders as well. I start the day off with magnesium spray to these areas which helps reduce the pain and stiffness. It is great news that the research world is starting to get funding for these orphan conditions.
sorry, now it works….
is it me or does your link not work? thanks!!!
Diseased monocytes correlating to the symptom severity (Grimson study) is an interesting one to me. I’ve been thinking that I still suffer from PEM, albeit at much lower severity, because a few diseased microglial cells still remain and they get activated at the same old PEM threshold.
Monocytes are essentially peripheral version of microglia, it seems to me. So, maybe they are similarly diseased in MECFS and similarly hypersensitive to low grade inflammation that is otherwise harmless.
Glad you corrected this. MH announced this in a very low key way on Twitter saying this was a $$ renewal. Great research but in a context of continuing abysmally low ME/CFS research funding, the decades ill ME cohort going to the back of the post-viral research queue and NIH fiddling the funding we do have, David Tuller revelation – we are very much waiting for our moment and need advocacy to highlight this.