It’s easy to get wrapped up in the-day-to-dayness and forget to look at the big picture. Looking back over the year, however, I was amazed at how much has happened and how many new possibilities have opened up. It’s been a remarkable year – particularly regarding the exercise findings in ME/CFS.
I hope you enjoy Health Rising’s 2019 edition of the Biggest, Most, Least and Worst things that happened this past year.
The “Thank God for New Technology” Award
Ian Lipkin brings the same disease busting technology to ME/CFS that he used to clear up acute flaccid myelitis – another mysterious pathogen-triggered disease. Hopefully, the second time is the charm.
The Most Fundamental Finding Award
Without oxygen, we’d be a blob of anaerobic bacteria lining the ocean floor. First, a Solve M.E.-funded metabolomics study suggested that the problem in ME/CFS isn’t broken mitochondria, but poor oxygen delivery to the muscles.
Then David Systrom, in a much bigger study, pegged systemic oxygen extraction (caused by both mitochondrial and circulatory problems) as the key problem in ME/CFS. Could oxygen delivery be the key issue after all?
The exercise studies continue to provide crucial insights into ME/CFS – none more so than a Norwegian 2-day CPET study which caught the process of post-exertional malaise in the act when it showed lactate accumulations increasing in ME/CFS patients during the second exercise day while the healthy controls’ lactate levels were decreasing…
The “How the Heck Did They Do That?” Award
The exercise breakthroughs continued when Nancy Klimas’s and Gordon Broderick’s computational biology groups were able to produce models that described how exercise goes wrong in ME/CFS. They used Klimas’s massive database gathered during exercise to produce computer models that not only described the immune, hormonal, etc. disruptions Klimas found but also predicted that exercise would also produce a hypersenstive immune system, inflammation in the brain and disruption of the blood-brain barrier. No wonder it hurts so much…
Best Anonymous Donation and Most Exciting New ME/CFS Research Center
Then comes Ron Tompkins (of $200 million in NIH awards) and his focus on what’s happening in the muscles of people with ME/CFS. Tompkins immediately lines up a bevy of collaborators to assist him in his new OMF-funded Harvard Collaborative Center – and then gets a near $400K anonymous donation – to start him on his muscle and blood studies.
Most Exciting Preliminary Finding
We’re not done with the exercise findings yet. Brian Walitt reports that the NIH intramural study is finding that exercise causes mitochondrial oxygen consumption (ATP production) to increase in the healthy controls but to decrease in about half of the ME/CFS patients. (That group sounds suspiciously like the lactate accumulators the Norwegian group found). The team has also found the oh-so-important B-cells “bottoming out” in the spinal fluid of ME/CFS patients.
Most Overdue Collaboration That’s Waiting to Happen
The exercise findings continued to role in. This time a massive, multi-study overtraining syndrome (OTS) effort suggested that test results do lie (or rather interpretations do). All the OTS test results were absolutely normal and abnormal at the same time; i.e. they were within normal levels but were significantly different from their healthy counterparts. The researchers’ finding that overtrained athletes were stuck in a “hypo-metabolic” state (sound familiar?) suggested that ME/CFS and overtraining syndrome is a collaboration that could not happen too soon.
Most Intriguing Potential Energy Tie-In
Talking about energy problems, in two presentations, Ian Lipkin suggested that lesions in the iron delivery processes in cells could produce anemia that’s present not in the blood but in the cells – echoing Birch’s suggestion that the anemia in ME/CFS is present in the tissues, not the blood. These are very preliminary findings but how interesting they are…
Most Intriguing Potential ME/CFS and FM Connection – We’re not done with energy at all… A gene expression study which found reduced expression of genes associated with energy production suggested that fibromyalgia may also be a “hibernation” disease, a disease in which – for whatever reason – the mitochondria have been turned down.
Best Presentation of the Year – Best Descriptor of the Year – and Best Conference of the Year) – not only was Australia’s Emerge’s livestreamed conference the best of the year but it also had the best presentation – a fascinating report from Paul Fisher, a mitochondrial specialist, who reported he’d found “the cellular equivalent to fatigue” lurking in ME/CFS patients’ mitochondria.
Possibly the Biggest, Best and Most Difference Making Study Ever – Which Doesn’t Contain a Single ME/CFS Patient
To top it off the NIH – which shirks at throwing its loose change at the “exertion intolerant disease” – ME/CFS – felt quite happy at throwing $170 million at an effort to understand the molecular roots of exercise in its “Molecular Transducers of Physical Activity Consortium” (MoTrPAC) project. That project likely won’t contain a single person with ME/CFS – and it must be noted that NIH Director Francis Collins missed a stellar opportunity to pump scads of money into a disease he says he’s so “troubled” about – but this deep, deep, deep dive into the molecular roots of exercise can only be superb news for ME/CFS. Exercise physiologist Staci Stevens called the project “a fantastic opportunity” for us.
Most Stubbornly Resistant – But Hopefully Soon Resolved – Hypothesis
Robert Phair’s compelling Metabolic Hypothesis has resisted easy validation – causing the resourceful Stanford researchers to come up with new methods to test it. In the latest in the Metabolic Hypothesis saga, Ron Tompkins will be sending muscle cells to Sweden to test it out.
The Most Irritating ME/CFS Study (For the British Biopsychosociologists (BPSs))
It was a simple study but what a potential impact. The Natelson/Unger study simply assessed symptoms against assessment scores to find that not only is ME/CFS not a somatization or a mood disorder but it doesn’t look anything like them. Its core symptoms are so different that adding a mood disorder to a ME/CFS diagnosis does’t affect them at all. Depression is simply an add-on disorder caused by the difficulty of the disease. ME/CFS has much in common with fibromyalgia, IBS, etc., which, sorry guys, are not somatization disorders either.
David Systrom, with his invasive cardiopulmonary exercise tests, seems to be collaborating with everyone possible in the Boston area including Ron Tompkins, Anne Oaklander, Michael VanElzakker, as well as Solve M.E.
After getting one of our few really big NIH grants, Mark Davis reported that the T-cell activation findings were not, at least at that point, working out. (Derya Unutmaz and Liisa Selim, however, are working on their own T-cell findings in ME/CFS.)
Second Biggest Disappointment
When last heard from, the exciting, seemingly rock-solid, made soooo much sense, red blood cell deformability findings did not appear to be working out either (sigh).
Best New Entry into the Field
What can you say when the creator of the functional MRI himself, Dr. Kenneth Kwong, is now working on ME/CFS in a Solve M.E. Ramsay Award – except to hope he sticks around…
Most Tantalizing Study Result We’re Waiting On
Jonas Berguist has reported several times that he’s validated Carmen Scheibenbogen’s findings of increased autoantibodies in ME/CFS. The next best thing to the report will be the actual study.
Highest Hopes for a Successful Grant Application
Ron Davis has been pouring grants into the NIH for years but his latest, a technology grant that would allow him to upgrade the nanoneedle, around which so much (diagnostics, drug trials) depends, may be his most consequential grant application yet. Let’s hope he gets it.
Best New Tool to Advance ME/CFS
Solve M.E.’s International Patient Registry – which includes Australia and the U.K. – should be here shortly.
Most Exciting New Pilot Study
Any time an experienced immunologist says something like this,
“In my long career of studying human T cell responses during viral infections I have never previously observed an increase in this cell type.”
there’s hope. From one of Solve M.E.’s 2019 Ramsay Awards.
Most Welcome Extended New ME/CFS Effort
It’s not a lot of money but it is a five-year commitment to fund ME/CFS – and those don’t come around often. Congratulations to Canadian advocates for getting the ball rolling in the federal funding arena in Canada and providing Canadian researchers some precious funds.
TREATMENT AND DIAGNOSTICS
2019 was a banner year for new diagnostic possibilities and that’s a good thing. It’s not as if the diagnostic dilemma that is ME/CFS got solved: in fact, diagnostics got more complicated this year as more diagnostic possibilities showed up that should help doctors better understand and treat their patients.
Most Surprising Leadership Position: FM and ME/CFS Lead Diagnostic Possibilities in 2019
Given how huge the medical field is, it was remarkable to see that no less than four of the top ten diagnostic news stories of 2019 involved ME/CFS or fibromyalgia in some way. They included Ron Davis’s nanoneedle test for ME/CFS, a fibromyalgia blood test, a blood test that measures the amount of pain one is in and a new Lyme disease blood test that diagnoses the disease in 15 minutes.
Not only is a definitive Lyme test now a possibility but the NIH recently greatly ramped up its effort to understand the baffling disease.
The Year of the Spine
2019 was truly the year that spinal problems – from craniocervical instability (CCI) to other brainstem issues to spinal stenosis to intracranial hypertension – came to the fore in ME/CFS. It’s become clear that spinal issues can cause, mimic or contribute to ME/CFS – throwing more diagnostic challenges into doctors’ laps. What’s not clear is how commonly they play a significant role. Three of HR’s five most read blogs for the year featured spinal issues.
Biggest Diagnostic Questions Raised
It’s still early days yet but Avindra Nath’s report that almost a third of the participants in the NIH’s small Intramural study were identified with a rare disease instead of ME/CFS raised all sorts of questions including “Do I have a rare disease? – and, if I do, “How in the world would I get diagnosed?”. The report indicated that the NIH was giving their study participants a workup like neither they nor we have experienced before.
Biggest Diagnostic Test Let Down
A U.K. research group’s study suggest that simple sample processing issues render the Booth-Myhill mitochondrial test unreliable.
Most Unlooked For – But in Retrospect, Most Totally Logical – New Subset
In a similar vein, Solve M.E. Ramsay Award winner Dr. Camille Birch found mutations in genes involved in production in 7 of 10 patients and very, very, rare mutations in glycogen storage genes in 2 of 10 patients – thereby adding glycogen storage disease to one of the possible missed diagnoses in ME/CFS. Birch suggested that anemia may be present in ME/CFS – not in the blood – but in their tissues.
Most Interesting ME/CFS Subsets Found
After extensively interviewing 60 ME/CFS patients during her Solve M.E. Ramsay Award work, Dr. Camille Birch came up with the following subsets:
- About 1/3rd described an infectious type onset.
- About 10% never felt normal, but the problem didn’t get bad until they hit their teen to adult years. This group slowly got worse over time.
- Another small group described an extremely rapid and massive onset triggered by a non-infectious event – surgery, trauma or other very stressful event.
- A few people described cognitive problems so severe that they sounded like they had something like Parkinson’s.
- Another group described really severe pain.
- Another group had really severe orthostatic intolerance.
These subsets make it very clear that more in-depth interviews could tell us much. Let’s hope that Birch has been expanding her fascinating surveys…
The “Did we really need another subset?” Award
Did we really need another form of orthostatic intolerance to pop up? Weren’t POTS, NMH, OH, VVS enough? Apparently not.
Dr. Peter Novak – another Harvard researcher (and colleague of David Systrom) – uncovered a new form of orthostatic intolerance called “hypocapnic cerebral hypoperfusion”. This group – which appears to be quite large – is often misdiagnosed as potential POTS but doesn’t exhibit either increased heart rates upon standing or a drop in blood pressure. Instead, a dramatic drop in CO2 levels and blood flows to the brain occurs when they stand. These patients can be diagnosed using an end-tidal CO2 test.
Second Most Interesting New Disease Subset
A study found that 15% of people with ME/CFS may have Non-Thyroidal Illness Syndrome (NTIS), a poorly diagnosed thyroid condition characterized by low free T3, increased reverse T3, normal or low TSH, and, if the condition becomes chronic, low free T4. NTIS typically occurs in starvation, sepsis and apparently – a group of ME/CFS patients.
Most Head-Exploding Finding
A large (but unpublished) study from Sweden suggests that an amazing 50-80% of people with ME/CFS have increased spinal fluid pressure (intracranial hypertension).
Best Failure-to-Recover Hypothesis
Dominic shows how patients who fail to recover after being in intensive care and people with ME/CFS may have a similar pattern of neuroendocrine dsyfunction. Somehow, that’s not that surprising.
The Still Waiting Award
In a record that’s unlikely to ever be surpassed we still await the results of potentially the biggest diagnostic study of all – the CDC’s ME/CFS expert multisite study which was funded in – wow – 2011…
Most Often Missed Diagnosis?
Dr. Bela Chheda reports that she finds small intestine bacterial overgrowth (SIBO) in most of her patients and that treating it can help with autoimmune processes. (Given that I’ve never had a SIBO test, that got me to thinking. She also regularly finds mast cell activation syndrome (MCAS)).
Most Shocking Fall
Citing allegations of sexual misconduct, Stanford, In a rare move, terminated the employment of longtime ME/CFS MD and researcher, Dr. Jose Montoya.
Most Surprising Possible Silver Lining
Dr. Montoya’s surprising departure does do one thing: it gives Stanford the opportunity to rethink an underperforming ME/CFS clinic, bring it up to date, integrate it with Ron Davis’s work, and enlarge it. Stanford signaled that they were on board – but time will tell. (A blog on the Stanford situation is coming up.)
Most Wished-For Battle
Stanford has an underperforming, rather isolated, ME/CFS clinic. Ron Tompkins has no clinic at all at Harvard, but says if he had the money, he already has the collaborators he needs to field a Center of Excellence NOW – setting up the wished-for battle – who has the best ME/CFS clinic in the land…
Best Result From a Drug Not Approved for ME/CFS or FM
One of a new breed of anti-CGRP drugs for migraine drugs disappears one person’s migraine and her FM – suggesting that the drug could help for FM – and by definition, perhaps ME/CFS as well.
Most Potentially Fruitful Repurposed Drug Trial
That made the news that – buoyed by its success with migraine, a drug manufacturer is now trialing its anti-CGRP drug in fibromyalgia – welcome, indeed. Given CGRP’s role in chronic pain and the impact the drug has on blood vessels, it only makes sense that it might work in FM
Best Start for an FDA-Approved Drug
Griffith University in Australia finds that an FDA-approved drug fixes the one big immune hole found in ME/CFS, so far – the NK cell cytotoxicity problems – in the lab, at least.
The Winner of the Happy-As-a-Pig-in-You-Know-What Award
The study design left something to be desired but the results were fascinating and encouraging. A British Clinic finds a 10-day fecal transplant trial returns the energy levels of 7/21 patients – all of whom had treatment resistant ME/CFS – to normal. Meanwhile a bigger Norwegian fecal transplant trial is underway.
Most Likely To Succeed New Drug
After dropping TNX-102 completely for awhile, Tonix is back with another big U.S. trial for a drug they hope will provide a double whammy for FM – and improve both sleep and pain. Given the drug’s success in PTSD and the simple fix (increasing the dose) for FM, it would be cruel (and unusual?) for the drug to fail again. Fingers crossed that we have a new drug for FM soon…
Most Anticipated ME/CFS Drug Trial Result
Cortene’s very small trial of a highly experimental drug – one that is not in use in other conditions, and was tested for the first time in ME/CFS – is successful enough for Cortene to move forward. A very small company, Cortene is now in the process of preparing another patent application, writing up the results of the trial for publication and raising money for another trial.
Second Most Anticipated Drug Trial Result
Nancy Klimas’s small ME/CFS trial involving etanercept and mifepristone has been reported to be underway several times. Hopefully it’s finished up by now and we’ll find what happened this year.
The Wait for “The Most Immediate Benefit to ME/CFS Patients” Report
It bears reminding that if it were not for David Systrom, we would never have heard of Mestinon. Systrom has reported that a paper assessing the effectiveness of Mestinon in ME/CFS is underway. Hopefully the results will be positive and doctors far and wide will be able to give this old-time FDA-approved drug a shot.
Most Exciting Upcoming ME/CFS Clinical Trial
Suddenly, ME/CFS is somewhat awash in small but intriguing clinical trials. After getting a nice infusion of cash, Naviaux’s Suramin ME/CFS clinical trial is due to begin this year.
Most UNLIKELY to Occur Drug Trial ?
The EpicGenetics BCG vaccine trial was slated to begin several years ago, then at the beginning of this year and again now, with the company not responding to questions – who knows?
Most Shocking Possible Drug Breakthrough
One hesitates to even the raise the possibility, but Dr. Peterson, the Simmaron Research Foundation, Maureen Hanson and the CDC are assessing new data on….Ampligen. A blog is coming up.
Strangest Possible Future Treatment Option
A potentially revolutionary finding suggests that antivirals – not probiotics – may be the cat’s meow for gut repair. It turns out that the viruses which infect the gut bacteria are in control of the gut flora. This Gulf War Illness study suggested that focusing on them may work very well, indeed.
Most Often Missed Drug Possibility?
Remy reviewed hers and others’ experiences with Nimodipine – a drug I had never come across – but which was featured decades ago in Dr. Goldstein’s treatment regimen, and formed the basis of Kristina D’Orr’s 2010 book on ME/CFS.
Most Amazing Recovery Story
Kyle McNease, healthy as a bull, gets whacked by something, falls apart, ends up signing power of attorney over to his parents, and then, as time is running out, finds out what started it all – a single toxic exposure from working on an old barn. Six months later, he’s back doing sprints again.
Funnest Clinical Trial – Dr. Natelson wants to rock you to sleep in order to help him learn more about the differences between fibromyalgia and ME/CFS.
Worst Performance – plunging individual grant applications tested the NIH’s commitment to ME/CFS. They failed that test miserably when both Francis Collins and Walter Koroshetz reaffirmed that no new funding for ME/CFS would be forthcoming.
Looking back – most puzzling use of the word “serious” – In an interview in 2015, NIH director Francis Collins said: “Give us a chance to prove we’re serious (about ME/CFS), because we are”. Four years later, with funding tumbling and grant application rates at an all-time low, one wonders what Collins means when he says he’s “serious” about something. Collins also said that he’s been “troubled” about the lack of answers for ME/CFS since 2009 when he became NIH Director. Between 2009 and 2015, adjusted for inflation, ME/CFS funding at the NIH fell to its lowest levels in decades.
Biggest Wakeup Moment for the NIH?
Tony Komaroff’s overview of ME/CFS in the Journal of American Medical Association (JAMA) scored – becoming one of the ten most viewed publications of the year, and underscoring the very, very (very) high interest in this disease.
The paper’s success suggested that the audience is out there, but they just need a little help, and if the NIH had the guts to do the right thing and poured some money – not a lot, but some money – into a funded grant application for ME/CFS, they might be very pleased with the result.
Most Disappointing Turnout
The NIH hoped its on-campus ME/CFS conference would spark interest in ME/CFS. In retrospect why that would happen pending some breakthrough findings in ME/CFS was unclear, but the event was poorly attended and funding has continued to decline.
Biggest Shoe About to Drop?
Jennie Spotila’s ace reporting revealed that with a number of major NIH grants will expire likely causing NIH funding for ME/CFS – already in decline – to decline even more next year.
Best NIH Moment of the Year
With funding declining and grant applications tanking, this has not been a good year for the NIH’s ME/CFS reinvigoration effort, but the strategic report underway provides hope that if the NIH won’t respond to advocates or its alarming statistics, it may respond to an internal, NIH-vetted report. We’ve wanted a strategic report for years and now – thanks to Vicky Whittemore and Walter Koroshetz – we’re going to get one.
Best Community Support
A three-way tie: David Tuller receives over 100K to continue his advocacy work on ME/CFS; ME Action got 100K (whoa!) from an anonymous donor; the Open Medicine Foundation blew through its December fundraising goal (and received an anonymous donation for $378,000 to fund its Harvard Center.
Best New Organization
The International Society for Environmentally Acquired Illness (ISEAI) shows up on the scene and produces its first international conference.
Most Ironic Departure – Carol Head recovered from ME/CFS decades ago but was forced to leave her position as President of Solve M.E. after several years struggling with a reoccurrence.
Greatest Fall – Not from a Mountain
Former Welsh mountaineer, Simon Parker, compares a winter mountaineering expedition during which he became hypothermic and almost died to the fatigue he now experiences walking upstairs.
HR’s Fundraising Update
As we near the end of the drive, a big, big thanks to the over 300 people who have contributed over $36,000 to HR.
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