NIH: Accelerating Research on ME/CFS meeting, 4th and 5th April 2019

I guess an angstrom per second is acceleration... ¯\_(ツ)_/¯

 

Yeah. I LOLed at P=10-9.

You don't see having to use notation instead of decimals often.

 

Just in case anyone missed David Systrom’s presentation ( he is very impressive), there is already a thread here where Llewellyn King talks to him. I intend to listen again before the conference presentation comes out.

https://www.s4me.info/threads/dr-da...nce-of-sfpn-in-some-patients.4855/#post-87180

 

Could not follow all the talks (it's really exhausting) but here's my short impression of the NIH conference:

There were some bad things. The online feed kept falling out, some presentations hardly said a word about ME/CFS and there were a lot of empty chairs. The people that were there and were asking most of the questions were either presenters or patients/carers. There doesn't seem to be a lot of interest from outside the field. Collins talked about how wonderful the NIH is, not about plans to further the ME/CFS field.

The talks on immunology and the microbiome showed that the research being done is really complex and that all sorts of fancy techniques are being used to study ME/CFS. That's hopeful but on the other hand, most of the findings were negative. If I remember correctly both the intramural and Lipkin study found no abnormalities in the NK-cells, The T-cell clonal expansion didn't work out and there isn't really a consistent finding that is being replicated by the different groups (except for TGF-beta, perhaps). The talks from Nancy Klimas, Jose Montoya, Jacksons Labs, and Cornell, were mostly about complex modeling. Unfortunately, I didn't have the feeling these researchers were on to something that could lead to a breakthrough in the near future. I like unexpected findings much more than complex modeling.

The talks on exercise tests were more interesting in that regard. Betsy Keller talked about chronotropic incompetence, the inability to increase the heart rate during exercise. Their review on this topic showed that many exercise test studies have reported this in ME/CFS patients. If I remember correctly Keller said her group had replicated this in a large cohort. She also reported that ME/CFS patients often show other abnormalities during exercises such as low ventilation or failure to increase blood pressure. To her, his all suggests autonomic dysfunction. Systrom seemed to agree with that, as he reported low filling pressure in ME/CFS patients - blood from veins not filling the heart as it should. This section of the talks was summed up by one of the persons asking questions. He said he was a researcher specialized in exercise intolerance and intrigued by the literature on ME/CFS. He claimed: "this is a cardiovascular disease until proven otherwise." Don't know if that is true, but the exercise researchers seemed to be on to something. Would be interesting if we had another research team like the Workwell Foundation, that tried to replicate their findings.

Then there were two interesting talks by the young researchers Younger and VanElzakker. Both are excellent speakers. They only had preliminary findings to report but seemed to have a lot of good research ideas regarding brain scans in ME/CFS. This seems like another promising field.

To me, the most intriguing finding came from the German researcher Bhupesh Prusty. His talk was about HH6 and the ability of this virus to disrupt mitochondria. He found that only a few ME/CFS cells were infected by the HH6 virus so this probably isn't the explanation. The interesting thing was that he reported reversible serum-induced mitochondrial alterations. In other words: there seems to be something in ME/CFS patients' serum that is changing the mitochondrial structure. And it's reversible, he said, if you wash it off, then the mitochondria turn normal again. Fluge et al. reported that there is something in the serum that affects mitochondrial function back in 2016. They wrote that "the cells exposed to ME/CFS serum displayed a metabolic change involving amplified lactate production under conditions of energetic strain." It's also similar to what Ronald Davis reported in his plasma swap experiment - if you put healthy cells in ME/CFS patients' serum, you get a signal on the nanoneedle device. But if you put a ME/CFS cel in healthy serum, there's no signal. This also suggests there is something in the serum. Davis said they don't think it's a metabolite or cytokine, but probably an exosome. He also said that it could very well be that the nanoneedle signal reflects changes in the mitochondrial structure.

There were some other interesting findings such as lower B-cells in the spinal fluid but not the blood, reported by the intramural NIH study. Ronald Davis tested the nanoneedle successfully in 10 more patients and has a paper accepted for this in the top journal PNAS. All in all, it was hopeful to see all these top scientists present their findings on ME/CFS.

 

erm...technically, in fact any ...ally, it's not.

What you are describing there is speed.

A very slow speed but a speed all the same.

Confusion is understandable given we aint going anywhere.

 

I'm not sure but I don't think so.

 

Yeah I meant that is our current acceleration We have been "accelerated". Apparently. No significant change in cruising speed, though. It's that hot air about "hope without action".

I think this will be it for some time, the will to do something simply isn't there. It will come down to technological progress ultimately. The human element is failing badly. The loss of human potential is enormous and met with a collective shrug and aloof yawns.

That's why political interventions such as the Norway resolution are necessary, no matter how it enrages the ideologues. Medical professionals and their institutional leaders are unable to understand the problem and so we depend entirely on progress filling the gap and politicians showing the leadership medicine can't muster.

So we'll be roughly going at the same speed in a few years, but cruising on a rolling road like they have at the airport.

At least we've eliminated many dead-ends. There's always that. Doesn't really change anything to the abysmal status quo of systemic neglect, however. That will probably take the idiotic New Age behavioralpsychosocial to crumble under its own weight.

 

Klimas has also started a Gulf War Illness clinical trial and is starting a parallel ME one as well based on various modeling strategies to determine possibilities given existing drugs.

 

For those who were concerned about empty seats at the conference...

Masur Auditorium has 488 seats. Before they removed the participants list from the conference site I counted 300 participants, but they removed it probably a month or so before the conference so more likely registered. I would guesstimate in total there were 325-350 people who attended the conference, particularly on the first day. So empty seats are simply because the venue was a bit oversized for the number of registered attendees.

 

There has been talk of that trial for well over a year now and nothing happening. OMF are the only ones with a real sense of urgency imo

 

I haven't seen much but was struck by orthostatic intolerance surfacing again and again. It is low hanging fruit as Bateman said. She also said that patients often don't realize they have it. That aligns with my suspicion that it is underdiagnosed.

The other low hanging fruit is probably the gut. Not sure if the dysbiosis is really the answer though. It could also be poor blood flow or nervous system problem.

Mast cells were also on the radar of several researchers.

The news that the thing in the blood that disrupts normal cell function seems to be exosomes is exciting. It makes me wonder if there is a way to figure out what cells are producing them.

I'm glad we have van Elzakker and Younger looking into neuroinflammation.

 

My take on this is that T-cell clonal expansion doesn't seem to work out for all patients. But for a subset it might be interesting. Neil MacGregor in the Australian conference, and Jarred Younger in his neuroinflammation talk at the NIH thought there was an auto-immune subset. If that is the case maybe if they can find what the T-cells are attacking using the techniques they are developing it could be useful information. I thought Lipkins "hunt" was interesting. A disease in Africa where the virus is long gone, but they found common auto-antibodies - want to apply the same peptide array techniques to their ME samples.

I too thought Bhupesh Prusty talk was very interesting - what an observant guy.

Add to the list Karl Morten who also identified that it was something in the patients blood that was affecting healthy muscle cells in his swap experiment. I really hope these guys can get funding to extend their swap experiments and hunt for the thing in the blood.

It wasn't until I watched this video in the embedded tweet that I realised that exosomes are a very new field.
https://twitter.com/user/status/1114297958994857984

 

I love this clip.
If i ever get better i plan to write a book resembling his fictional Sane Planning, Sensible Tomorrow

 

I believe from an interview with her that Nancy Klimas' has been having to work out how to get this done without cash for it. Sorry there's no hope of me remembering where I saw that.

 

The women's study is funded and the men's study is over half way there. She is waiting for IRB approval to begin both studies.

 

Yes, I saw this too. I know Klimas has tried multiple times to get government funding for a trial on another drug. I believe this is private funding and she now has funding from the dept of defense for GWI

 

I'll try to post some positive things from the conference to keep myself afloat here. As always, correct me if I got something wrong.

Not so many rare diseases after all; 90%+ of the patients were ruled out on the phone, most of those over not fitting the criteria. Most of the others were ruled out for having an inflammatory diseases, I'm assuming a lot of them had an autoimmune disease + CFS. Of the 22 patients that made it, only 3 were found to have something else, and 1 of those was a very rare cancer and 1 parkonsonism.

Keller seems to think the disease is surprisingly uniform in 2-day exercise testing, and Systrom findings are similar (if his exclusion of non preload failure patients is appropriate).

Interesting biological findings (maybe we can make a list, to have it in one spot)

1) Low B-Cells in the CSF (NIH) (I guess sub-types needed to understand this)

2) 44% of patients with Small Fiber Neuropathy

3) I only watched 2 presentations so I'll need help!

 

Random thought of mine. I saw somewhere the comment that, broadly speaking, only researchers in the later stages of their careers and researchers early in their careers were in attendance. While it can't be proved, my opinion is that this is one of the legacies of the psychologisation of ME, a good 25 to 30 years of biomedical researchers put off from getting involved.

The positive point is obviously that young researchers are getting involved - another comment I saw somewhere suggested that NIH were surprised by the attendance at the young researcher event.

 

Vicky has replied already, and said that she will take a look at the forum - everybody behave yourselves now!

 

She should look at this discussion on OI. It's been brilliant. How about referring her to our top10 threads?!

(Link to split thread added by moderator)