Ronald W. Davis, PhD's presentation at the IIMEC13

[alex3619]

I find the observation that cell function seems to improve after a bacterial infection is very interesting, and I hear this occasionally from patients.

Hypothesis and test is one phase of a larger cycle. Focusing on one step limits the effectiveness of science.

Showing the severity of ME/CFS is much worse than a range of other severe diseases is helpful, but its not necessarily objective.

Aside from a few patients, ME/CFS patients have less viral load than healthy controls. RNA viruses have not been properly tested yet. They are also exploring exhaustive genetic sequencing looking for unknown viruses.

They are working on a general parasite test. Sleeping sickness not only has a nearly identical gene match to ME/CFS, but it has almost identical sickness. The one that amazed me, and I missed in my own review many years ago, was that its less about sleeping too much than about having an inverted circadian rhythm, sleeping during the day and not at night. I have discussed this with many patients and seems to be common in patients sick longer than three years, including me and several of my ME friends. So one hypothesis being tested is that African Sleeping Sickness IS CFS.

Many nutritional metals, used in detox, are very low.

They are planning to compare our metabolimics to gene changes, looking for a metabolic trap. Hypothetically this means the onset can be very sudden, within hours. I was involved in metabolic regulation for ME in 1993, as a patient and giving some very limited analytic advice. They should hopefully know in months to a year. Treatment under this hypothesis might be easy, fast and cheap, once we know exactly what is going wrong.

A lot of the glucose we have is shunted to fat synthesis.

Suramin might be available by the end of the year, and he pointed out its also used for Sleeping Sickness. I was hoping someone would look into this, and it looks like it will happen maybe next year.

 

[alex3619]

expressing preference for one theory or another.

Having preference is fine. However its the science, and the testing of ideas, that determines if they are right or not, or right for subgroups.

 

[mariovitali]

So one hypothesis being tested is that African Sleeping Sickness IS CFS.

My question here is whether African Sleeping sickness patients present with the neurological/psychological/hormonal multitude of Symptoms seen in ME/CFS

 

[Forbin]

So one hypothesis being tested is that African Sleeping Sickness IS CFS.

Well, it can't be exactly African Sleeping Sickness, since, untreated, that will kill you in a few months to a few years, depending on which type you get. The East African version kills you most quickly, which is interesting, as it is the type in which it is more difficult to detect the trypanosomes.

 

[alex3619]

My question here is whether African Sleeping sickness patients present with the neurological/psychological/hormonal multitude of Symptoms seen in ME/CFS

Ron Davis implied that yes, we do, but this has not been formally investigated. There may be important differences.

 

[alex3619]

Well, it can't be exactly African Sleeping Sickness, since, untreated, that will kill you in a few months to a few years, depending on which type you get. The East African version kills you most quickly, which is interesting, as it is the type which is more difficult to detect.

The hypothesis is that either its something that produces similar biochemistry, or its a different typanosome or similar parasite. I was first aware of parasites tracking with ME in the early 2000s, in this case a tropical roundworm found natively in south east Asia. Parasite investigation has been only limited in ME research.

 

[Hutan]

I haven't heard about the roundworm @alex3619. Can you say anything more about that?

It seems an unlikely candidate as presumably some anti-worm medication would quickly sort it out (we certainly tried such medication early on), and surely it wouldn't be very hard to find. And there would need to be some creative thinking to have a tropical roundworm account for ME around the world. But still, I'm interested.

 

[alex3619]

I haven't heard about the roundworm @alex3619. Can you say anything more about that?

I think there is a thread on PR on this worm. I was in contact with the researcher in the early 2000s, who was in California, but I forget almost everything now. NONE of the standard medications even touch this parasite. The parasite was named after him.

 

[alex3619]

PS I do recall its hard to find. Blood tests at the time always failed. He found it in sputum. The cardinal sign was little inflammatory dots in a line on the skin.

PPS He had the same name as a famous TV show producer, again I cannot recall the name.

PPS Larry Klapow https://www.prohealth.com/library/new-parasite-found-in-chronic-fatigue-syndrome-cfids-16154

 

[Jenny TipsforME]

I am going to continue to believe that ME is a particular condition brought down upon people who thought they could think through things just to prove that they can't

Loving this! I think it is a theory I should tell myself several times a day. I did find myself googling stuff Ron mentioned as if I could work it out and then told myself “if Ron doesn’t understand the connection yet the likelihood I can work it out by googling papers is almost zero”

I also agree with @Trish that it can be next to useless for us to be for or against theories based on a hunch. Though of course our lived experience is valuable- if it just doesn’t match our experience we should say very loudly so Research money isn’t wasted.

There’s a danger in identifying too closely with any particular theory because all the current theories could be wrong. People were very upset by the XMRV saga.

that i find the metabolic trap hypothesis simplistic.

My impression is Ron was quite clear to say his explanation was very simplified. I don’t think they’re saying the biology of it is simple. My (next to useless) hunch is that this does have legs as a general approach to finding what’s wrong.

I think they need to find a way remission would be explained though - they seem to think we can’t happen upon a way to reset our metabolic trap but plenty of us go into remission so there must be something we’re inadvertently doing?

The concept that it could be deliberately reset in a few days is mind blowing. This gives me hope that a positive end could be in sight. Although I also hold that in tension with a sense it could be a very unrealistic expectation.

cell function seems to improve after a bacterial infection is very interesting, and I hear this occasionally from patients.

I think I remember having this once. I assumed it was the antibiotics. Although new infections scare me I also try to think that it could be that my immune system resets in a functional way afterwards (further deterioration isn’t the only outcome). Though this seems like a myth.

A similar quirky thing that needs investigating is being brainfog free pre virus. I do get brief, random brainfog free windows in everyday life but the day before I get a new virus I can think like a healthy person (I don’t mean viral PEM symptoms I mean catching a virus that’s going around). Several other pwme have said the same.

 

[andypants]

A similar quirky thing that needs investigating is being brainfog free pre virus. I do get brief, random brainfog free windows in everyday life but the day before I get a new virus I can think like a healthy person (I don’t mean viral PEM symptoms I mean catching a virus that’s going around). Several other pwme have said the same.

Me too.

 

[Simon M]

Diagnostic tests
First 20 minutes of video are about their new diagnostic technologies. My notes, FWIW:

Biomarker: the primary concern is to demonstrate that patients are sick, rather than finding differences with other diseases.


Nanoneedle chip: uses a single drop of blood (red blood cells removed) and measures electrical impedance with 25,000 tiny gold electrodes. ME/CFS patients and healthy controls both initially give a flat line over time. Adding sodium chloride (table salt) puts am energy demands on the cell, which must pump out sodium to stay alive. Continued flatline response from cells of healthy controls but rapid increase in impedance from patients' cells.


All all patient samples had a much higher impedance than controls, P = 10 ^ -7.
(I assume that someone will shout if I shouldn’t be sharing this, but it is already available in the video already)

Plasma swap experiment shows the issue is with plasma not cells. Healthy cells with ME/CFS plasma behave like patient samples, while ME/CFS cells with healthy plasma behave like healthy controls i.e. no increase in impedance.

Gives real-time results and if made commercially could cost five dollars or less. They are also using this approach for drug screening; looking at the drugs that normalise the behaviour of ME/CFS cells.


Capillary testing of red blood cells: less deformability and slow attracts transit speeds for ME/CFS patients' red blood cells. Not clear if this is a physiological effect, being tested as a diagnostic. Does not currently give clean separation from healthy controls: researchers will make smaller capillaries which Ron Davis leaves will give a clear separation from controls . Inexpensive.


Researchers have reported similar deformability findings in ME/CFS in the past (1990s, I think).


Magnetic "levitation"


This clever approach uses a special magnetic fluid and applies a magnetic field tothe fluid. This great to density gradients. Cells are laid on top of the fluid and start to settle, the cells settle at different rates according to their cell density and also there unique "magnetic signature".


Initially developed this method to separate free tumour cells in the blood, partly because cancer is more fundable and that allowed them to develop the technology to use on ME/CFS. They enhanced the technology so it could not only separate but also collect the different cell types e.g. collecting circulating tumour cells from the blood. Running costs are five cents per run. Ron Davis said they could make a portable machine to do the diagnostic test for around $1000.


They have tested pre-existing technology, Seahorse, which measures cellular metabolism (glycolysis and oxidative phosphorylation). They found that using stimulated T cells gives most consistent results (n = 6/8); other groups use all white blood cells, I think.


Diagnostic Bake off! Use 4 different methods and see which one works best. Nanoneedle, magnetic levitation, capillary test, Seahorse. Use Naviaux’s metabolomics as the reference for diagnosis.


Could combine multiple tests for greater accuracy.


Next step would be to test with comparable diseases; they will consult with physicians to see what would be useful.

 

[Sly Saint]

Next step would be to test with comparable diseases

are they doing any kind of collaboration with Nancy Klimas (GWI) with this.......could bring in the $$s

 

[alex3619]

Plasma swap experiment shows the issue is with plasma not cells. Healthy cells with ME/CFS plasma behave like patient samples, while ME/CFS cells with healthy plasma behave like healthy controls i.e. no increase in impedance.

This has been known for many months now, but its nice to see again. This might mean that its dangerous for us to give blood, but this is not certain. It might also mean that ME can be transmitted via blood transfusion ... Kenny DeMeirleir looked into that in the 90s, and based on a personal conversation (I think, its been so long) he found that the odds of ME appear increased after a blood transfusion. Unfortunately I am not aware of any formal study of this.

 

[alex3619]

Researchers have reported similar deformability findings in ME/CFS in the past (1990s, I think).

Yes. I followed the work of Les Simpson back then.

 

[alex3619]

I did find myself googling stuff Ron mentioned as if I could work it out and then told myself “if Ron doesn’t understand the connection yet the likelihood I can work it out by googling papers is almost zero”

I think this is very likely correct most of the time. We can however get ideas about what might help us, and experiment. This also exposes us to risks that we might harm ourselves. That is one of the reasons why details of the metabolic traps they suspect are not public, as most simplistic treatments might be harmful.

 

[ScottTriGuy]

This has been known for many months now, but its nice to see again. This might mean that its dangerous for us to give blood, but this is not certain. It might also mean that ME can be transmitted via blood transfusion ... Kenny DeMeirleir looked into that in the 90s, and based on a personal conversation (I think, its been so long) he found that the odds of ME appear increased after a blood transfusion. Unfortunately I am not aware of any formal study of this.

 

[Alvin]

Aye carumba

 

[alex3619]

@ScottTriGuy thanks for that link. I forgot it was a presentation, it shows how much I have forgotten. I was at that conference. I presented my own hypothesis there. Doh. That was the first time I talked with KDM as well, and spoke to Ellie Stein, amongst others. I also heard about stealth viruses and other suspected infections. It was also the first time I heard, from our Australian expert, that while Lyme disease here is mostly from overseas, about seven cases per year could not be accounted for by overseas travel, so there must be an indigenous source.

There is some data about blood transfusion transmission, but we still cannot be sure why or what might be transmitted. I asked the question earlier because this large molecule in the blood that triggers our cellular dysfunction would trigger it in others. The issue though is whether or not it would be just temporary, or if it could trigger the full disease.

 

[junkcrap50]

This has been known for many months now, but its nice to see again. This might mean that its dangerous for us to give blood, but this is not certain. It might also mean that ME can be transmitted via blood transfusion ... Kenny DeMeirleir looked into that in the 90s, and based on a personal conversation (I think, its been so long) he found that the odds of ME appear increased after a blood transfusion. Unfortunately I am not aware of any formal study of this.

@ScottTriGuy thanks for that link. I forgot it was a presentation, it shows how much I have forgotten. I was at that conference. I presented my own hypothesis there. Doh. That was the first time I talked with KDM as well, and spoke to Ellie Stein, amongst others. I also heard about stealth viruses and other suspected infections. It was also the first time I heard, from our Australian expert, that while Lyme disease here is mostly from overseas, about seven cases per year could not be accounted for by overseas travel, so there must be an indigenous source.

There is some data about blood transfusion transmission, but we still cannot be sure why or what might be transmitted. I asked the question earlier because this large molecule in the blood that triggers our cellular dysfunction would trigger it in others. The issue though is whether or not it would be just temporary, or if it could trigger the full disease.

Could a CFS patient be cured or have improvement by receiving a blood transfusion (or seveal) from a healthy person? A healthy relative maybe with known health history? Any cases of that? Since Ron Davis has said that sick, CFS cells have returned to normally functioning, healthy cells when placed in healthy patient's blood/serium, that seems like it could be possible.