NIH intramural research program update

[Sasha]

I have a suspicion that people like Mady Hornig, Oysten Fluge, Amolok Bansal, Juliá Blanco, Carmen Scheibenbogen, James Baraniuk, and Jo Cambridge might think 'hmm, strange that we did all the tests we could possibly think of and struggled to find anything, and when we did find something, it did not look like any standard pattern anyone got before'. This was more or less the conclusion from the IiME workshop last year - people are finding things but not in line with giveaway cell signatures - if anything back to front of that. I don't want to dampen any spirits but a few other people have tried slaying this particular Minotaur in ten easy steps.

Do you think there's something they're not doing that they should be doing, that we could suggest to them?

 

[Jonathan Edwards]

If they've done all the tests they could think of and have drawn a blank, where do they go or what do they do next ?

Is it reasonable enough for the NIH to start from scratch so to speak, and maybe pick up on something that hasn't been done before?
Or are you saying more or less all the NIH testing has been done before ? ( excluding pre and post exercise I presume )

I am not discouraging anyone from doing lots of tests. I guess I am suggesting that it may be optimistic to think anything is going to jump out at researchers in a small sample as being typical of NK cells or B cells or somthing.

 

[searcher]

Probably a bit late, but here are some cleaned up slides that are a bit easier to read for the Nath presentation.
http://www.meaction.net/2016/02/16/transcripts-and-slides-from-dr-naths-talk-on-nih-study/
Read the transcript from #MEAction. Watch the video, starts at 42'38"

Thanks Simon! I updated the MEAction post with the slides, and added in the initial Rituximab one.

 

[Bob]

The "Aim 2" slide says "metabolic studies". Does anyone know what that might mean in this context?

The "Aim 3" slide says "Auto antibodies directed against the brain". Can anyone remember if any researchers have tested for these before in ME patients?

The "Aim 4" slide describes the animal model; they are going to inject cerebro-spinal fluid and antibodies from ME patients into the brains of rodents and humanized mice, to see if it induces an ME-like illness or symptoms in the animals. That could be interesting. The humanized mice will have been "generated with cells from PI-ME/CFS patients". Does anyone know what a humanized mouse is in this context? (Sorry if this has been discussed already.)

 

[BurnA]

I am not discouraging anyone from doing lots of tests. I guess I am suggesting that it may be optimistic to think anything is going to jump out at researchers in a small sample as being typical of NK cells or B cells or somthing.

Ok. If the initial tests don't clearly point to t or b cells or whatever, then I wonder what their plan is then.

In terms of the additional or follow on tests do we know how many of these would already have been completed in studies to date ?

 

[Forbin]

I'm a bit concerned that although transcranial magnetic stimulation (TMS) can be used in the diagnosis of problems related to the communication between the brain and the muscles, it has also been investigated as a treatment for a variety of psychiatric disorders including treatment-resistant major depressive disorder (MDD), schizophrenia, panic disorder and OCD.

I realize that many ME/CFS patients report "muscle weakness," but is this really thought to be of similar origin to the muscle weakness seen in stroke or ALS (for which TMS can be used for diagnosis)?

I guess I'm saying that I'd like to know whether there are any intentions of using TMS as an experimental treatment in this study.

 

[Scarecrow]

The "Aim 3" slide says "Auto antibodies directed against the brain". Can anyone remember if any researchers have tested for these before in ME patients?

How about auto antibodies to muscarinic receptors in the Schiebenbogen paper from last year?

http://www.sciencedirect.com/science/article/pii/S0889159115300209

 

[viggster]

Ok. If the initial tests don't clearly point to t or b cells or whatever, then I wonder what their plan is then.

In terms of the additional or follow on tests do we know how many of these would already have been completed in studies to date ?

Well they're looking at more than just immune cells. They're doing proteomics on CSF, for instance. And looking at the microbiome. And looking at mitochondria. And looking at neurons made from patients' stem cells.

 

[viggster]

I'm a bit concerned that although transcranial magnetic stimulation (TMS) can be used in the diagnosis of problems related to the communication between the brain and the muscles, it has also been investigated as a treatment for a variety of psychiatric disorders including treatment-resistant major depressive disorder (MDD), schizophrenia, panic disorder and OCD.

I realize that many ME/CFS patients report "muscle weakness," but is this really thought to be of similar origin to the muscle weakness seen in stroke or ALS (for which TMS can be used for diagnosis)?

I guess I'm saying that I'd like to know whether there are any intentions of using TMS as an experimental treatment in this study - and, if so, whose bright idea that might be.

Well it's not a treatment study...it's a deep investigation into the biology of ME. According to this review article, "TMS can be used to evaluate excitatory/inhibitory intracortical circuits and to provide information on brain physiology and pathophysiology of various neuropsychiatric diseases as well as on the mechanisms of brain plasticity and of neuroactive drugs." So it sounds like it might have some diagnostic value in ME.
http://www.ncbi.nlm.nih.gov/pubmed/17296913

And here's a good time to remind people that adding your question to this list being compiled by the US Action Working Group (the group of 30+ advocates who recently came together) is the most efficient way to ask NIH a question. At some point the questions will be relayed to contacts at NINDS.
http://www.meaction.net/2016/02/12/usawg-submits-questions-to-the-nih/

 

[viggster]

Does anyone know what a humanized mouse is in this context? (Sorry if this has been discussed already.)

That usually means mice that have a human-derived immune system, like these critters made at the Jackson Lab in Maine.
https://www.jax.org/jax-mice-and-services/in-vivo-pharmacology/humanized-mice

 

[Forbin]

According to this review article, "TMS can be used to evaluate excitatory/inhibitory intracortical circuits and to provide information on brain physiology and pathophysiology of various neuropsychiatric diseases as well as on the mechanisms of brain plasticity and of neuroactive drugs." So it sounds like it might have some diagnostic value in ME.

Thanks! I also found this very detailed introduction to transcranial magnetic stimulation (TMS) authored by the senior investigator at the NINDS Human Motor Control Section (the mission of which is "to understand the physiology of normal human voluntary movement and the pathophysiology of different movement disorders"). The author is very highly regarded and was once the clinical director of the NINDS.

He is also one of the investigators listed on Dr. Nath's slides.

http://www.sciencedirect.com/science/article/pii/S0896627307004606

 

[BurnA]

I'm a bit concerned that although transcranial magnetic stimulation (TMS) can be used in the diagnosis of problems related to the communication between the brain and the muscles, it has also been investigated as a treatment for a variety of psychiatric disorders including treatment-resistant major depressive disorder (MDD), schizophrenia, panic disorder and OCD.

I realize that many ME/CFS patients report "muscle weakness," but is this really thought to be of similar origin to the muscle weakness seen in stroke or ALS (for which TMS can be used for diagnosis)?

I guess I'm saying that I'd like to know whether there are any intentions of using TMS as an experimental treatment in this study.

From the transcript

“Aim two of the study is to define the physiological basis of fatigue using functional MRI scan of the brain to define the brain circuits that are involved. Do detailed metabolic studies in a metabolic chamber and do transcranial magnetic stimulation as well as very detailed autonomic testing. Each of these tests will be performed before and after exercise.”

 

[Tuha]

I have a suspicion that people like Mady Hornig, Oysten Fluge, Amolok Bansal, Juliá Blanco, Carmen Scheibenbogen, James Baraniuk, and Jo Cambridge might think 'hmm, strange that we did all the tests we could possibly think of and struggled to find anything, and when we did find something, it did not look like any standard pattern anyone got before'. This was more or less the conclusion from the IiME workshop last year - people are finding things but not in line with giveaway cell signatures - if anything back to front of that. I don't want to dampen any spirits but a few other people have tried slaying this particular Minotaur in ten easy steps.

it´s frustraiting to see that just the design of this study is already so controversial and raise many questions and concerns.
The governements say all the time that they want to move ME further and faster but they are just talking for years and they still didnt put significant amount of money to help to create ME research. I dont have any scientific background but to read this thread is not very encouraging. After NIH and Collins announcement last year I hoped that the things will develope much faster in our favour. Maybe I am wrong but I see only another uncertainty and probably we will lose other years again unefficient.
Jonathan, I know that you probably cannot talk too much but I think you have a lot of inside informations. Do you think that the researchers who you mentioned are much further to understand ME and that their understanding could lead us soon to a treatment? I know that there is Rituximab, Lipkin´s studies,... but I have impression that these findings came out already long time ago and the last years we didnt hear almost anything what would bring us further.

 

[BurnA]

I dont have any scientific background but to read this thread is not very encouraging. After NIH and Collins announcement last year I hoped that the things will develope much faster in our favour. Maybe I am wrong but I see only another uncertainty and probably we will lose other years again unefficient.

I wouldn't be too discouraged. It's not perfect but it's a big start, is the way I look at it. My interpretation of Dr. Edwards comments is that maybe it's not quite as easy as the NIH make it sound, which is probably to be expected.

I am actually surprised how fast this has taken shape.

 

[Jonathan Edwards]

it´s frustraiting to see that just the design of this study is already so controversial and raise many questions and concerns.
The governements say all the time that they want to move ME further and faster but they are just talking for years and they still didnt put significant amount of money to help to create ME research. I dont have any scientific background but to read this thread is not very encouraging. After NIH and Collins announcement last year I hoped that the things will develope much faster in our favour. Maybe I am wrong but I see only another uncertainty and probably we will lose other years again unefficient.
Jonathan, I know that you probably cannot talk too much but I think you have a lot of inside informations. Do you think that the researchers who you mentioned are much further to understand ME and that their understanding could lead us soon to a treatment? I know that there is Rituximab, Lipkin´s studies,... but I have impression that these findings came out already long time ago and the last years we didnt hear almost anything what would bring us further.

Dear Tuha,
Science is a strange thing. When you think you are making progress you often look back and think not much happened. When you think nothing is working you may look back and say 'that was the break point when we began to see how it works'. Lots of things are going on and any one of them may turn out in retrospect to have been a key breakthrough, but you only know afterwards. What I can say for sure is that the quality of expertise focused on ME/CFS now is like never before. And funding breaks seem to be coming - like this project.

 

[Tuha]

thanks for the answers. It´s not easy to wait all these years. Hopefully we already made that break point. It would be great and encouraging to have more informations but I understand that the scientists cannot inform us too much

 

[Aurator]

It would be great and encouraging to have more informations but I understand that the scientists cannot inform us too much

I don't think scientists are reticent, generally speaking, once they're confident they've made some kind of genuine discovery; the fear that some other scientists somewhere may discover the same thing and get all the credit for it tends to make scientists want to spill the beans almost as soon as there are any to spill. By the same rule, though, no scientists worth their salt will want to make announcements to the world prematurely.

 

[Cheshire]

Brian Walitt video: Fibromyalgia doesn't fit the disease model (9 minutes)

http://www.familypracticenews.com/s...e-model/e913134880916685f3005dac5459ab88.html

A whole transcription of this appalling video is now available on #MEAction website: http://www.meaction.net/2016/02/20/nih-lead-clinical-investigator-thinks-cfs-is-psychosomatic/

More worrisome quote:

Nothing exists without your brain creating those sensations for you and the idea that that process of creation can create these things and is supposed to create things like this to inform us and to teach us and to guide our behavior pushes against the idea that we have free will and that we can do whatever we want and that we should be able to lead the lives that we have always thought we should lead–not the ones that our bodies are restricting us to. And so accepting those kind of ideas is not so easy–that might make it a little bit easier on everybody; that might be a more palatable narrative, understanding that, you know, people can feel bad for no real fault of their own, because of the circumstances of lives and how brains just work–the way it’s supposed to be–as opposed to being sick.

Yes PWFibro should just accept that their state is normal (how could suffering like hell be part of normality?), accept their disability, they should accept that there are people that are destined to crappy lives and stop dreaming to have a normal life like mine.
Ethically disgusting.
Patronising.
Illogical: PWFibro experience an abnormal life but it results from normal biology.

 

[olliec]

Thanks to everyone who has been collating what we know about all the investigators in the NIH study in MEpedia. If you've seen any especially relevant articles, studies, talks or interviews re investigators (especially those of concern) please add them:
http://me-pedia.org/wiki/NIH_Post-Infectious_ME/CFS_Study#Investigators

The other investigators are Ana Acevedo (physiatrist), Jeffrey Cohen (infectious disease & virology), Bart Drinkard (physical therapist), Luigi Ferrucci (geriatrician & epidemiologist), Penny Friedman, Fred Gill, David Goldstein (neurocardiology), Mark Hallett (neurology & motor control), Wendy Henderson (gastrointestinal immunology), Silvina Horovitz (neurology & motor control), Steve Jacobson (virologist), Eunhee Kim, Mary Lee (psychoneuroendocrinology), Tanya Lehky (electromyography), Jon Lyons (allergy), Eugene Major (virologist), Adriana Marques (Lyme disease, virology), Carine Maurer (neurology & motor control), Joshua Milner (T cells, allergy), Leorey Saligan (cancer fatigue), Stephen Sinclair (psychologist), Bryan Smith (neurology), Joseph Snow (neuropsychologist), Stacey Solin (nurse), Neal Young (immunology, bone marrow), Jay Chung (metabolism).

 

[Snowdrop]

A whole transcription of this appalling video is now available on #MEAction website: http://www.meaction.net/2016/02/20/nih-lead-clinical-investigator-thinks-cfs-is-psychosomatic/

Words fail. I wish I could unsee this.