Coverage from IACFS/ME Florida conference, 27-30 Oct 2016

[Jonathan Edwards]

Thanks for the information. Any thoughts on possible explanations for the discrepant results, other than randomness?

All sorts of possibilities I guess. I think it illustrates just how careful one has to be about interpreting clinical trials.

 

[Freddy]

The information comes from Dr Carmen Scheibenbogen in Berlin. It has nothing to do with the Beiger interview although it may have been mentioned there. I am fairly sure there is no publication but the information has been shared with the research community. I agree that we do not know much about inclusion criteria but I doubt these are a major issue. Some cases were very unwell even if not strictly in the severe category (which did not give good responses in Norway).

Although I very much hope the phase III rituximab study is positive I think we should still be cautious.

Thanks for the reply, Prof. Edwards. I agree that the inclusion criteria might not be an issue, there are very careful at the Charite.

I was aware of some bad adverse reactions, but did they really say, no single positive response out of 10!? Really?

We are speculating at the moment. And I understand the reluctance of sharing sensitive information. Would be interessting what they actually shared with you...

Maybe I should try to ask them at my next appointment.

 

[Gingergrrl]

I was aware of some bad adverse reactions, but did they really say, no single positive response out of 10!? Really?

Freddy, do you mean that there were some really bad reactions to plasmapheresis or IVIG in the Charite study or are you talking about a study with RTX? Sorry for my confusion!

 

[BurnA]

Can we keep the thread on topic ?
There are plenty of RTX threads and also the thread @Sidereal linked to already is worth reading before everyone gets too distracted.

 

[Sidereal]

The information comes from Dr Carmen Scheibenbogen in Berlin. It has nothing to do with the Beiger interview although it may have been mentioned there.

Actually it was more than 'mentioned' in the Beiger interview. He reports that at that point he knew of 10 people who had been treated at Charite with RTX and 8 of them had no response and 2 got worse, including the football player who ended up in a wheelchair in a nursing home unable to look after himself. While I agree that the Phase III trial will offer much more useful information than these anecdotes, people should be aware that there are cases out there of worsening not just in Germany but also reported anecdotally from the other two clinics that have been using it off label in people who say they have ME/CFS, whatever that means to different people.

 

[Navid]

It is complicated from a physical perspective. Dr Davis just has a gift of explaining difficult things in simple terms. Its 18nm technology for a start (v small!). But Dr Davis did say that it doesn't need to be so complicated, its what they have at the moment. Hopefully in future it will be less complicated. (To paraphrase).


B

Unfortunately cannot hear RD's presentation. Is there any twitter feed that details what he presented....very curious to hear his news.

Thanks

 

[ash0787]

Unfortunately cannot hear RD's presentation. Is there any twitter feed that details what he presented....very curious to hear his news.

Thanks

maybe someone will write it up into an article, in summary though he has in his possession a precision engineered
object which you fill with pre-seperated blood and then it measures the electrical resistance of individual cells,
he said when a cells health decreases its electric impedance increases, this can differentiate between normal peoples cells and cfs cells provided that a certain salt is added to the mixture to force the sodium pumps to activate thus depleting ATP at a higher than normal rate.

 

[ZeroGravitas]

Livestreamed videos available from the OMF's Facebook page.[...] https://www.facebook.com/OpenMedicineFoundation/videos/956825444421877/

Just saw this on Fb and watched it through, scribbling (i.e. bashing) down some fairly haphazard, indescrimate notes on what I could make out and follow.

There was Jon D. Kaiser MD (from 00:00), Dr. Nancy Klimas (15:40), Ron Davis (36:00).

Spoiler: Open for big long mass of jibberish...

* Jon D. Kaiser MD (00:00)

There were 50 papers on mitochondrial dysfunction in chronic illness in 2000, but 1800 in 2015!

54 quintillion ATP molecules in the body (normally).

Difficult to get a test that directly measures mitochondrial energy production.

P31 MRI scanning - peering into different tissues to measure ATP directly.

Seahorse (Agilent) - flux anylyser device - measures mito function in white blood cells. Know this is reduced in e.g. Parkinsons where brain mitos also dysfunctional.
http://www.agilent.com/en-us/promotions/xftechnologyoverview [Cool equipment/method videos there.]

BHI - Bioenergetic health index summarizing mito function.

Early HIV drugs killed mitos too. So he formulated a nutrient support formula to support mitos. Then switched to CFS field.

Using cloud connected actigraphy(?) devices (pedometers?) to objectively measure patient response while keeping them blind to feedback (more objective).

Question 1. About increased oxidative stress in aging population in general...

Even healthy controls have a wide variance of mitochondrial function. So maybe those with lowest function will be more likely to get sick first...

Q2. Borderline mito function would make all organs more susceptible to damage when stressed.

Q3. Methyl-phenidate is a dopamine agonist...(?)

* Dr. Nancy Klimas (15:40)

Video by group at Harvard of computational simulation of the cellular mechanisms working in cells. [

? Fairly old now.]

Microscopy videos of energy being delivered down microtubules.

Paula Rizzario(?) - tomorrow will show microscope slices video of EBV proteins migrating to and attaching to the wall of the mitochondria.

1 in 3(?) cells have latent virus of some kind, that could be reactivated and make viral stuff, partial virus = enzymes that can still mess things up.

Trying to deal with the complexity (of cells connected and acting on others far away, etc) by using a computation biology platform strategy.

We've done studies with patients on an exercise bike. When you push energy production to the anaerobic state it initiates an inflammatory cascade in CFS patients.

All metabolism pathways turn off (opposite of normal) and cell communication turns off (e.g. cortisol production turns *off*).

Cells are jam packed with mitochondria. But here there are fewer, and so should metabolite levels (like glutathione) related to per cell, or per mito? (We don't know.)

Is this (mitochondrial dysfunction) adaptive (protective) or just the problem? Down-regulating to protect against increasing oxidative stress that would be very damaging, causing cell death and tissue degeneration.

CoQ10 supplementation produced effect if measured levels also improved...(?) It takes a lot to replenish stores (but then you're topped up and then you're there).

In current study they're using 400mg ubuiquinol (equivalent to 1200ml ubiquinone). Then will measure results, reduce to 200mg, then re-meausure(?).

But substances like this that aid energy make sleep worst, dose dependently.

They also have Seahorse equipment. Talking of various methylation, liposomal glutathione studies...

Thinks this sound be the home and a forum for gulf war illness (too).

Q1. Computational platforms have been indicating targets for therapies. They show you have to fix more than one thing at once - combination therapies.

Gulf war consortia have provided many tools to movee faster by looking at a lot of things before human trials.


Q2. Where does the iron go? (Most pwCFS very deficient.)

Iron from dead brain cells is very damaging.

4th panelist(?) - They have taken an NMR measurement of it(?).


Q3. Curcumin into cells... [Video skip glitch 33:00]

nf[Capa][Beta] something.

Q4. Gulf war question, toxic exposures, etc - talk about that at another time.

* Ron Davis (~36:00):

Wanted to show us 2 instruments that they've built (but no AV for seeing the slides).

Metabolon via 'Thermal Fischer'(?) instruments.
[http://www.metabolon.com/ | http://www.thermofisher.com/uk/en/home.html ?]

There are about 4000 metabolites in the blood, total. Half from bacteria in gut. Metabolon wrote the software to deal with all this.

They spent $20-$50k of their own money to analyse his son as a first patient, 2 years ago.

Mitochondria dysfunction immediately jumped out at Ron within 5 seconds (citric acid cycle depleted, etc). Glucose appeared to be getting shunted across to making fatty acids. Burning amino acids.

[?] was also doing similar metabalom work, so didn't compete with him to publish, just communicated, since he's trying to fast track usable results.

Launched big data study with OMF, with huge amount of data - $1.5M spent on 20 patients.

May find many false positives, but also be able to decide what to look at the next time around. (Could do with $40-$50M! Hah.)


Q1. Problem with another group's data colection...(?) 23andMe, only found 1 haplogroup A. Double the amount of 'no call' across the 25 patient study (mtDNA)?


Q2. No one's currently doing mtDNA testing on clinical patients.

Ron doesn't recommend it currently.

New instruments:

a) Built an instrument that's put atop a mobile phone camera (clever tricks to examine almost atomic scales!?).
Separates out cells by magnetic levitation in a capillary tube.
Results in ~20min.

E.g. can look for change in density of cells as a result of killing tumor cells with a drug.

b) New (genetic?) sequencer that runs on a phone (hopefully for $1000)...

c) Use electrical impedance measurement (through and around a test cell).

Wants to build an assay that lets you test drugs on cells, as a CFS model alternative to human/animal trials.

This could test every single FDA approved drug in 1 to 2 years. Using Stanford nano-fabrication capabilities (down to 18nm resolution).

Sit cell in tiny channel with many electrodes either side and take electrical impedance measurements 100 times per second.

Healthy white cells have fairly steady impedance when stressed, needing ATP. While CFS cells, after 2 hours, have great increase in impedance.

Stress them by adding sodium chloride so the cells have to turn their pumps on.

Result might be an artifact. Also it's a very tough setup for anyone else to do, so hoping it is overly complex and simpler can be constructed.


Q3. [CFS is?] Something in the serum (or missing from it).

[Video upload lost connection... Second (10minute) video: https://www.facebook.com/OpenMedicineFoundation/videos/956878351083253/]

Don't just test baseline samples, do symptom provocation and next day too. Creatine kinase(?) equilibrium. Needed to uncover mitochondrial dysfunction.

Klimas - take blood samples 10 times across exercise provocation. Line up data in a clever way, but still need to repeat study to confirm finding...

Challenges with subjects when they are going to induce crashes.

...[I ran out of steam.]

4th panalist - [?]

As I say, not at all coherent, and apologies for not picking out any name drops (particularly bad at making those out), but perhaps someone might pick something up from in there. By all means correct mistakes, or rather, just leave it be and watch the video first hand. ;-)

I thought it was particularly interesting to hear all the context of what's going on and that Ron and others are working on white blood cells as standard (all of them, I think he said, just removing the RBC), which seems pretty relevant for the discussions we've had about the recent paper finding increased non-mitochondrial ATP production in PBMN cells (up to here so far). Particularly whether or not these immune cells are very badly suited to being representative of mitochondrial metabolism in the rest of the body, etc.

[Edited - added a few screen shots.]

 

[Navid]

maybe someone will write it up into an article, in summary though he has in his possession a precision engineered
object which you fill with pre-seperated blood and then it measures the electrical resistance of individual cells,
he said when a cells health decreases its electric impedance increases, this can differentiate between normal peoples cells and cfs cells provided that a certain salt is added to the mixture to force the sodium pumps to activate thus depleting ATP at a higher than normal rate.

Thanks Ash: So basically he and his team have invented a device to determine who has CFS? WoW!!!!

Was there any actionable news for patients shared in terms of treatment and or being tested to determine if we do in fact have CFS. ( I know give em an inch and they want a mile; those darn sick people) : )

Thank you ASH!!!

 

[Ben H]

Just saw this on Fb and watched it through, scribbling (i.e. bashing) down some fairly haphazard, indescrimate notes on what I could make out and follow.

There was Jon D. Kaiser MD (from 00:00), Dr. Nancy Klimas (15:40), Ron Davis (36:00).

Spoiler: Open for big long mass of jibberish...

* Jon D. Kaiser MD (00:00)

There were 50 papers on mitochondrial dysfunction in chronic illness in 2000, but 1800 in 2015!

54 quintillion ATP molecules in the body (normally).

Difficult to get a test that directly measures mitochondrial energy production.

P31 MRI scanning - peering into different tissues to measure ATP directly.

Seahorse (Agilent) - flux anylyser device - measures mito function in white blood cells. Know this is reduced in e.g. Parkinsons where brain mitos also dysfunctional.
http://www.agilent.com/en-us/promotions/xftechnologyoverview [Cool equipment/method videos there.]

BHI - Bioenergetic health index summarizing mito function.

Early HIV drugs killed mitos too. So he formulated a nutrient support formula to support mitos. Then switched to CFS field.

Using cloud connected actigraphy(?) devices (pedometers?) to objectively measure patient response while keeping them blind to feedback (more objective).

Question 1. About increased oxidative stress in aging population in general...

Even healthy controls have a wide variance of mitochondrial function. So maybe those with lowest function will be more likely to get sick first...

Q2. Borderline mito function would make all organs more susceptible to damage when stressed.

Q3. Methyl-phenidate is a dopamine agonist...(?)



* Dr. Nancy Klimas (15:40)

Video by group at Harvard of computational simulation of the cellular mechanisms working in cells. [

? Fairly old now.]

Microscopy videos of energy being delivered down microtubules.

Paula Rizzario(?) - tomorrow will show microscope slices video of EBV proteins migrating to and attaching to the wall of the mitochondria.

1 in 3(?) cells have latent virus of some kind, that could be reactivated and make viral stuff, partial virus = enzymes that can still mess things up.

Trying to deal with the complexity (of cells connected and acting on others far away, etc) by using a computation biology platform strategy.

We've done studies with patients on an exercise bike. When you push energy production to the anaerobic state it initiates an inflammatory cascade in CFS patients.

All metabolism pathways turn off (opposite of normal) and cell communication turns off (e.g. cortisol production turns *off*).

Cells are jam packed with mitochondria. But here there are fewer, and so should metabolite levels (like glutathione) related to per cell, or per mito? (We don't know.)

Is this (mitochondrial dysfunction) adaptive (protective) or just the problem? Down-regulating to protect against increasing oxidative stress that would be very damaging, causing cell death and tissue degeneration.

CoQ10 supplementation produced effect if measured levels also improved...(?) It takes a lot to replenish stores (but then you're topped up and then you're there).

In current study they're using 400mg ubuiquinol (equivalent to 1200ml ubiquinone). Then will measure results, reduce to 200mg, then re-meausure(?).

But substances like this that aid energy make sleep worst, dose dependently.

They also have Seahorse equipment. Talking of various methylation, liposomal glutathione studies...

Thinks this sound be the home and a forum for gulf war illness (too).

Q1. Computational platforms have been indicating targets for therapies. They show you have to fix more than one thing at once - combination therapies.

Gulf war consortia have provided many tools to movee faster by looking at a lot of things before human trials.


Q2. Where does the iron go? (Most pwCFS very deficient.)

Iron from dead brain cells is very damaging.

4th panelist(?) - They have taken an NMR measurement of it(?).


Q3. Curcumin into cells... [Video skip glitch 33:00]

nf[Capa][Beta] something.

Q4. Gulf war question, toxic exposures, etc - talk about that at another time.



* Ron Davis (~36:00):

Wanted to show us 2 instruments that they've built (but no AV for seeing the slides).

Metabolon via 'Thermal Fischer'(?) instruments.
[http://www.metabolon.com/ | http://www.thermofisher.com/uk/en/home.html ?]

There are about 4000 metabolites in the blood, total. Half from bacteria in gut. Metabolon wrote the software to deal with all this.

They spent $20-$50k of their own money to analyse his son as a first patient, 2 years ago.

Mitochondria dysfunction immediately jumped out at Ron within 5 seconds (citric acid cycle depleted, etc). Glucose appeared to be getting shunted across to making fatty acids. Burning amino acids.

[?] was also doing similar metabalom work, so didn't compete with him to publish, just communicated, since he's trying to fast track usable results.

Launched big data study with OMF, with huge amount of data - $1.5M spent on 20 patients.

May find many false positives, but also be able to decide what to look at the next time around. (Could do with $40-$50M! Hah.)


Q1. Problem with another group's data colection...(?) 23andMe, only found 1 haplogroup A. Double the amount of 'no call' across the 25 patient study (mtDNA)?


Q2. No one's currently doing mtDNA testing on clinical patients.

Ron doesn't recommend it currently.

New instruments:

a) Built an instrument that's put atop a mobile phone camera (clever tricks to examine almost atomic scales!?).
Separates out cells by magnetic levitation in a capillary tube.
Results in ~20min.

E.g. can look for change in density of cells as a result of killing tumor cells with a drug.

b) New (genetic?) sequencer that runs on a phone (for $1000)...(?)

c) Use electrical impedance measurement (through and around a test cell).

Wants to build an assay that lets you test drugs on cells, as a CFS model alternative to human/animal trials.

This could test every single FDA approved drug in a year and a half. Using Stanford nano-fabrication capabilities (down to 18nm resolution).

Sit cell in tiny channel with many electrodes either side and take electrical impedance measurements 100s times per second.

Healthy white cells have fairly steady impedance when stressed, needing ATP. While CFS cells, after 2 hours, have great increase in impedance.

Stress them by adding sodium chloride so the cells have to turn their pumps on.

Result might be an artifact. Also it's a very tough setup for anyone else to do, so hoping it is overly complex and simpler can be constructed.


Q3. [CFS is?] Something in the serum (or missing from it).

[Video upload lost connection...]

Don't just test baseline samples, do symptom provocation and next day too. Creatine kinase(?) equilibrium. Needed to uncover mitochondrial dysfunction.

Klimas - take blood samples 10 times across exercise provocation. Line up data in a clever way, but still need to repeat study to confirm finding...

Challenges with subjects when they are going to induce crashes.

...[I ran out of steam.]

As I say, not at all coherent, and apologies for not picking out any name drops (particularly bad at making those out), but perhaps someone might pick something up from in there. By all means correct mistakes, or rather, just leave it be and watch the video first hand. ;-)

I thought it was particularly interesting to hear all the context of what's going on and that Ron and others are working on white blood cells as standard (all of them, I think he said, just removing the RBC), which seems pretty relevant for the discussions we've had about the recent paper finding increased non-mitochondrial ATP production in PBMN cells (up to here so far). Particularly whether or not these immune cells are very badly suited to being representative of mitochondrial metabolism in the rest of the body, etc.

Nice job @ZeroGravitas


B

 

[Christian Godbout]

To add to what @ash0787 said above, Ron Davis says this precision device would thus allow to measure PEM at a cellular level (no need to stress the entire person into PEM… just blood cells), he says it would also constitute by far the fastest way to test drugs (without using humans entire, or animals - just cells) and could allow to test every existing FDA approved drug in 1-2 years! And as he shows the audience this neet little device I think we hear Klimas enthusiastically call it "Cool!" and she adds something like "I tell you, Nasa is going to want one!". That's how far ahead Davis just might be: Rocket science!

 

[Forbin]

It was somewhat difficult to hear, but Dr. Davis mentioned the development of a device that attaches to the camera of a smart phone (like an iPhone) which performs some kind of magnetic levitation-based cell sorting. The computing power of the iPhone then performs an optical blood assay using the iPhone's camera. It's very inexpensive (~5 cents/assay) and quick ("you can see the results in about 20 minutes"). An example that he gave was that you could see if a cancer drug was killing cancer cells.

Another device in development is a chip which measures electrical impedance to evaluate cellular changes. The main use Dr. Davis discussed for such a device would be to assess the effects of various drugs on cells. Part of the goal is to develop an assay using cells which "show the behavior of chronic fatigue syndrome." He said such technology had the potential to allow them to test every drug ever approved by the FDA in the span of one-to-two years.

Currently, using this assay, healthy cells and CFS cells show the same impedance until they are stressed by creating "a demand for ATP." After about 2-hours, the CFS cells show a reproducible increase in impedance. "That's an assay," Dr. Davis said - by which I think he meant that it's a reproducible test for CFS. He likened it to seeing PEM at a cellular level.

Earlier, he also mentioned a separate device - a "sequencer" that (I believe) is run using an iPhone's computer and would only cost $1000. I assume he's talking about genetic sequencing using an iPhone and a $1000 "peripheral."

I hope I got most of this right. [Just realized this repeats some info from posts above.]

 

[Kati]

Seen on twitter:

https://twitter.com/i/web/status/792057198478254081

 

[Sasha]

Thanks very much for that summary, @ZeroGravitas!

Wow, that iPhone assay thing... wow...

 

[Sasha]

Seen on twitter:

https://twitter.com/i/web/status/792057198478254081

She's not kidding. Makes the UK look mediaeval.

 

[alex3619]

he says it would also constitute by far the fastest way to test drugs

Drug test beds like that can accelerate research dramatically. A decade of research can be compressed to a few months if you have funding.

 

[NL93]

I am so impressed with Ron Davis. He is remarkable.
Let's give him and the OMF a lot of money for more research! It really bothers me that there is a lack of money. I know the NIH is really supposed to be funding this but they are not currently doing that. There are millions of patients worldwide- if everyone would just make a small donation, we can move forward a lot faster.

 

[usedtobeperkytina]

This is probably the most striking (and heartbreaking) tweet of today's presentations at IACFSME:

https://twitter.com/i/web/status/791640500579233792

Among these 100, how many were patients/caregivers? How many were doctors? How many were researchers?

I agree. However, we are seeing new researcher names and faces. Maybe more will be there on Sat and Sun.

 

[Kati]

I agree. However, we are seeing new researcher names and faces. Maybe more will be there on Sat and Sun.

Hi @usedtobeperkytina from what I understand this presentation was made on patient day, so considering the expense of time, energy and money, patients for the most part are unable to attend for one reason or another.

 

[Never Give Up]

I just discovered that the Bateman-Horne Center is also tweeting from the conference.

https://mobile.twitter.com/BatemanHorne