Prof Stephen Holgate talk to patients/EdMesh: Understanding mechanisms of ME/CFS

[Simon]

Prof Stephen Holgate's talk to EdMesh in June was videoed by them and is now online

The slides are available at Slideshare: New Inroads into Understanding the Mechanisms of CFS and ME

I haven't seen the video myself yet, just the slides, and I think it's an updated version of the talk I blogged about here: A Dozen Different Diseases? Stephen Holgate Calls for Radical Change in ME/CFS Research (that blog was based on the minutes of the Forward ME group where he presented, I didn't get to see the talk myself).

 

[Scarecrow]

Thanks, Simon

I had intended to go to this talk but I forgot all about it long before it happened. I didn't know I'd missed it until now. Oh, the joy of ME.

I highly recommend the video to everyone. Don't be put off by the poor quality sound at the start - it soon gets sorted but you'll need to turn the volume up. Stephen Holgate's a good speaker and he presents at a nice measured pace for the ME brain.

 

[Gemini]

Prof Stephen Holgate's talk to EdMesh in June was videoed by them and is now online

Thank you for posting Prof Holgate's high-level overview of the future direction of ME/CFS research @Simon.
Such an inspiring, important & hopeful message...

He cites cancer treatment as an example of successful "Personalized Medicine." He might find Dr. Jerome Groopman's Sept 15, 2014 New Yorker article "The Transformation" interesting. Seems 15% of AML patients (a subset) are found to have a mutated enzyme for which the experimental drug AG-221 is proving highly effective. Remarkably the drug doesn't kill cancer cells but rather "fixes" them. One cancer researcher is quoted: "These data signal the first real advance for AML in thirty years...."

http://www.newyorker.com/magazine/2014/09/15/transformation-3

Prof. Edwards is discussing ME/CFS subsets here on PR. Let's hope we'll see real advances with this approach as well.

 

[A.B.]

I'm warming up to Holgate. Even though it is not clear what exactly he has in mind, he does seem to understand that the current circumstances are dire and urgently need to change.

 

[Sean]

Don't want to get people's hopes up, but I got the distinct impression from that video that the psychs are being quietly but firmly sidelined. Holgate used what in the circumstances was some fairly strong language.

We have every reason and right to be sceptical until we see some serious practical results from all this. But I am not displeased with Holgate's presentation and political finessing. All things considered, it is about as good as we could reasonably hope for in the short term.

The pyschs' stranglehold on this field is not going to be broken overnight, and the benefits of that long overdue disempowerment are not going to reach patients for a while yet. But I think it is finally starting to happen.

 

[ukxmrv]

I've lost my hope in Professor Holgate and this talk reinforces it. Much of it is about the future and it's not relevant to us at this stage.

When I heard a recording of Professor Holgate talking to the Cornwell group(?) a few years ago it sounded very promising. He used the same arguments about respiratory funding and the way he had turned that around. The only duff note in that talk was when he appeared to want to have Dr Crawley has the leader of the (what was then) the new MRC group.

Since then he has not invigorated the MRC ME research group with new scientists receiving funding into critical or important areas. Dr Newton has been funded but she was already involved in this area and funded by MERGE. There is nothing else useful to us either being funded or about to start that we know of.

I am alarmed by aspects of his talk. We seem to be replacing ME with a syndrome displaying symptoms of fatigue and pain of no known origin. It's the Ideopathic Chronic Fatigue of our nightmares.

Examples

"We brought ME scientists (of which there were very few ) together with other scientists who study the brain, pain.."

He didn't bring in scientists who study the immune system. Why not? Where are the neurologists? Where is Dr Chaudhuri and Dr Behan? He didn't bring in scientists who study infectious diseases.

He didn't bring in scientists who study exercise physiology. In fact PEM as a defining symptom of ME doesn't exist.

Pain - where is the evidence that he has included scientists who study anything other than centralisation theories?

Brain - what good is this going to do us? Why was Dr Puri not involved or any doctors with ideas on brain scan abnormalities, low blood flow to the brain. I have a feeling that when he says brain he means something else. I think he means brain if it only affects psychiatric symptoms or similar. He's not talking lesions.

He says that ME is a "complex interaction". I'm not sure if that isn't leading us back to pain centralisation and the "brain".

He says I think that "ME not a disease any more" - I'm not good about this. What good does this us?

So he has decided that ME is not a disease any longer, that it is a complex interaction (and put together scientists who are involved in either the psych side of sickness behaviour or pain centralisation or who say that there are no current infections in patients (like Lloyd) but not the ones finding abnormalities) and treating patients or who have looked at brain abnormalities or muscle biopsy's.

A whole foundation of work has been dumped.

He appears to have disregarded the entire non-psych body of research into ME and CFS. Dr Ramsay may not have existed, there were no outbreaks of ME. Professor Behan and muscle biopsies. The physical findings on autopsy. The doctors treating infections. The Lights' work on PEM. The Snell group on PEM.

It's all gone

ME has been replaced by a fatigue and pain set of symptoms. An ideopathic chronic fatigue with pain. Nothing more.

 

[Wildcat]

.

CCC, ICC, PEM, seem to have gone out the window too.

 

[MeSci]

Thank you for posting Prof Holgate's high-level overview of the future direction of ME/CFS research @Simon.
Such an inspiring, important & hopeful message...

He cites cancer treatment as an example of successful "Personalized Medicine." He might find Dr. Jerome Groopman's Sept 15, 2014 New Yorker article "The Transformation" interesting. Seems 15% of AML patients (a subset) are found to have a mutated enzyme for which the experimental drug AG-221 is proving highly effective. Remarkably the drug doesn't kill cancer cells but rather "fixes" them. One cancer researcher is quoted: "These data signal the first real advance for AML in thirty years...."

http://www.newyorker.com/magazine/2014/09/15/transformation-3

I'm afraid I can't get excited about cancer drugs. We frequently get the 'breakthrough' announcements, then it all goes quiet or we find out that the effects don't last or the side-effects are too bad.

A friend of mine has had leukaemia for many years - admittedly a different type from that referred to in the article - but the example may be of interest.

She was on a clinical trial of ibrutinib - it was her last hope as chemotherapy had stopped working. After an initial stage of unpleasant side-effects she had dramatic improvement. Then it stopped again.

She was being considered for another experimental drug but there was a delay. In the meantime, both she and a fellow-patient had further remissions with no drugs at all!

I know this is about cancer, but the same kind of thing happens with many new drugs, which look promising but then the effects wear off And many have to be withdrawn due to serious adverse effects.

Obviously those involved in the research will talk up the efficacy.

 

[Simon]

I've lost my hope in Professor Holgate and this talk reinforces it. Much of it is about the future and it's not relevant to us at this stage...

Examples

"We brought ME scientists (of which there were very few ) together with other scientists who study the brain, pain.."

He didn't bring in scientists who study the immune system. Why not? Where are the neurologists? Where is Dr Chaudhuri and Dr Behan? He didn't bring in scientists who study infectious diseases....

I'm not going to go through the detail here, but I think that's a very strange way to view his presentation. As for immunologists and neurology and infectious diseases, the keynote speakers at the CMRC conference he set up were:

• Prof Robert Dantzer, who pioneered the study of the interaction of the immune system and the brain
• Prof Andrew Lloyd, an immunologist, who reported on the extraordinary Dubbo study, looking at ME/CFS developing after several different infections inc EBV/glandular fever. And he found psychosocial factors did not predict subsequent CFS, but severity of the initial infection did, as did the type of cytokine gene. Report coming soon
• Prof Ian Lipkin, who heads up the Center for Infection and Immunity, has discovered more viruses than anyone else on the planet and is running a series of large pathogen and immune (and more) studies on ME/CFS

Honestly, what's not to like?

As for 'not a disease' he's saying it's not a single disease. He gives numerous examples including 'breast cancer' which turns out not a single disease, but many. Causal molecular pathways are his thing. Read more about his views here: A Dozen Different Diseases? Stephen Holgate Calls for Radical Change in ME/CFS Research

 

[ukxmrv]

I'll just stick to Andrew Lloyd for now as that is the one I know the most about.

Have you read Osler's Web? Do you remember the part about Dr Lloyd acting for an insurance company against a nurse who had a needlestick injury and developed CFS.

He's been in a lobby for decades now that says that there is no ongoing infection, virus or anything to treat in CFS. None of his patients are prescribed antiviral drugs. He tells his patients that they do not have any reason to be tested for ongoing virus or any other pathogen activity. His patients don't get treatment beyond what a UK Fatigue Clinic.

I know about the Dubbo study and have since it was first mentioned. My "take home" message is different. The Dubbo study to Dr Lloyd is about a virus attack that has come and gone. He's been vocal about his ideas.

"Indeed Lloyd later in an interview said “We believe that the parts of the brain that control the perception of fatigue and pain get damaged during the acute infection phase of glandular fever. If you’re still sick several weeks after infection, it seems that the symptoms aren’t being driven by the activity of the virus in body, it’s happening in the brain.

“It’s not too big a leap of faith to say after that, it’s in the brain, because of the nature of the symptoms – it’s fatigue, it’s pain, sleep disturbance, concentration and memory difficulties and mood disturbance. They’re very much brain symptoms.”

"Perception of fatigue and pain get damaged"

With friends like this who needs enemies.

 

[MeSci]

I know about the Dubbo study and have since it was first mentioned. My "take home" message is different. The Dubbo study to Dr Lloyd is about a virus attack that has come and gone. He's been vocal about his ideas.

"Indeed Lloyd later in an interview said “We believe that the parts of the brain that control the perception of fatigue and pain get damaged during the acute infection phase of glandular fever. If you’re still sick several weeks after infection, it seems that the symptoms aren’t being driven by the activity of the virus in body, it’s happening in the brain.

“It’s not too big a leap of faith to say after that, it’s in the brain, because of the nature of the symptoms – it’s fatigue, it’s pain, sleep disturbance, concentration and memory difficulties and mood disturbance. They’re very much brain symptoms.”

"Perception of fatigue and pain get damaged"

With friends like this who needs enemies.

Can't remember what the Dubbo studies are about - my brain has not been working at all well the last 2 days - but effects in the brain can be due to the gut or to microglia. Does Lloyd know that?

 

[ukxmrv]

Can't remember what the Dubbo studies are about - my brain has not been working at all well the last 2 days - but effects in the brain can be due to the gut or to microglia. Does Lloyd know that?

There's a starter on the Dubbo studies here

http://phoenixrising.me/research-2/...t-infective-fatigue-forming-the-dubbo-studies

 

[Simon]

Can't remember what the Dubbo studies are about - my brain has not been working at all well the last 2 days - but effects in the brain can be due to the gut or to microglia. Does Lloyd know that?

Yes - and he's interested in looking at activation of brain microglia as one of the most promising areas of CFS/ME research.

As @ukxmrv said, he found no evidence of ongoing infection (ie not difference between fatigued cases and recoverd controls) and no difference in long-term cytokine levels either - though they did find evidence that if you have a more aggressive cytokine response to the initial infection you are more likely to develop CFS/ME (all this has been published). So his views are shaped by the evidence he found. Anyway, full report coming soon.

 

[Esther12]

Lloyd did write that paper claiming that the letters published in the Lancet pointing out some of the problems with PACE were "unscientific and sometimes personal attacks": http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2796.2011.02468.x/full

Pretty hard for anyone who has actually looked at the letters cited to defend that.

(Saying that, I don't have a problem with some of the other things he's said).

 

[ukxmrv]

Yes - and he's interested in looking at activation of brain microglia as one of the most promising areas of CFS/ME research.

As @ukxmrv said, he found no evidence of ongoing infection (ie not difference between fatigued cases and recoverd controls) and no difference in long-term cytokine levels either - though they did find evidence that if you have a more aggressive cytokine response to the initial infection you are more likely to develop CFS/ME (all this has been published). So his views are shaped by the evidence he found. Anyway, full report coming soon.

Are you sure his views were not shaped before then?

Osler's Web certainly gives that impression plus there are the patients who have seen him in Australia.

http://medicalsciences.med.unsw.edu.au/community/lifestyle-clinic/services/fatigue-clinic

LIFESTYLE CLINIC
Services » Fatigue Clinic

The term chronic fatigue syndrome (CFS) is commonly used to describe the illness in general medical practice in which unexplained fatigue is the dominant complaint. Despite the lack of knowledge as to the pathophysiology of CFS and by extension the lack of treatment options targeting the cause(s), a number of interventions have been investigated 1.

To date the most promising results have been achieved with cognitive behavioural therapy (CBT) [2-6] or graded exercise therapy (GET) [4,7,8].

The Fatigue Clinic is an integrated rehabilitation clinic developed in collaboration with Professor Andrew Lloyd - an internationally recognised leader in the study of the pathogenesis and management of medically unexplained fatigue - and the exercise physiologists at the Lifestyle Clinic.

 

[Scarecrow]

Lloyd did write that paper claiming that the letters published in the Lancet pointing out some of the problems with PACE were "unscientific and sometimes personal attacks": http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2796.2011.02468.x/full

Pretty hard for anyone who has actually looked at the letters cited to defend that.

(Saying that, I don't have a problem with some of the other things he's said).

I agree that the letters are markedly free of personal attacks. Very odd that they should be cited. One or two made frequent use of quotations, which can come across as a bit sarcastic sometimes but, oh my, you'd have to be very touchy to take it personally.

As for unscientific, up to a point that's a matter of opinion.

Lloyd's co-author (and I would think the principal author of the comment on the ICC consensus paper) was Jos W. M. van der Meer of the Department of Medicine and Nijmegen Institute for Infection. One of the BPS brigade?

 

[Scarecrow]

Are you sure his views were not shaped before then?

Osler's Web certainly gives that impression plus there are the patients who have seen him in Australia.

http://medicalsciences.med.unsw.edu.au/community/lifestyle-clinic/services/fatigue-clinic

LIFESTYLE CLINIC
Services » Fatigue Clinic

The term chronic fatigue syndrome (CFS) is commonly used to describe the illness in general medical practice in which unexplained fatigue is the dominant complaint. Despite the lack of knowledge as to the pathophysiology of CFS and by extension the lack of treatment options targeting the cause(s), a number of interventions have been investigated 1.

To date the most promising results have been achieved with cognitive behavioural therapy (CBT) [2-6] or graded exercise therapy (GET) [4,7,8].

The Fatigue Clinic is an integrated rehabilitation clinic developed in collaboration with Professor Andrew Lloyd - an internationally recognised leader in the study of the pathogenesis and management of medically unexplained fatigue - and the exercise physiologists at the Lifestyle Clinic.

Regarding the bit I've bolded, I think that's the problem (if it's a problem). If you take a very inclusive view of 'fatiguing illnesses', it may be likely that you'll have patients that benefit from CBT and GET.

At the 'Lifestyle Clinic' - and doesn't that name just set your teeth on edge - they have an exercise physiologist, so at least there is some kind of assessment going on.

I suppose that there are variations of CBT and GET and that they don't all have to be a la PACE.

Many years ago, my neighbour, who had heart problems, enrolled for a prototype group CBT course. She found it useful. I wouldn't go anywhere near CBT for any illness. I just don't have a receptive personality for it. (I'm one of those people that hate all that participatory, touchy feely, morale building, ice breaking stuff beloved of HR trainers; just give me the facts, then leave me alone to get on with it and stop patronising me thank you very much!)

I recently met someone who'd done GET and vouched for it. If you're physically able, who doesn't like to go for a walk? But if the level of activity induces PEM, not such a good idea.

 

[Valentijn]

Lloyd's co-author (and I would think the principal author of the comment on the ICC consensus paper) was Jos W. M. van der Meer of the Department of Medicine and Nijmegen Institute for Infection. One of the BPS brigade?

Yup.

 

[MeSci]

Maybe Lloyd has seen the light, but is too discreet/timid/professional/loyal - or unwilling to discredit his previous work - to diss his former colleagues openly?

 

[WillowJ]

or maybe Lloyd was asked to come and talk on that one particular study, as it seems more useful than some of his other papers (it is not his most recent paper, which seems most typical for a presentation at a conference)