NIH awards £1m grant to UK Biobank

[Firestormm]

I agree with your thoughts. I think it's half of the £1m. And my guess is that the other half goes towards running the biobank for another 3 years. (I think they said it would keep it running for another 3 years?)

Yeah. The 'press statement' didn't break it down, but the Biobank project does include the longitudinal study. So the remaining amount (not listed on the link you kindly provided) must be for 'associated running costs' [my term] I flagged this up on MEA Facebook, Charles might know and I'll reply here if so

 

[SpecialK82]

The study sounds absolutely awesome - exactly what we have always needed!!

So, we have now discovered how to get money out of the NIH - we just need other countries to ask for it!

Come on Canada, Australia, all of Europe ------- how much would you guys need to actually cure this thing?

 

[*GG*]

Well, I'm happy to have been bought for £1 million!

Me too, that's not even a Million pounds, right? I just hope it is fruitful, there seems to be lots of research going on at independent orgs in the USA and I like what is going on in Australia, perhaps something positive and reinforcing some previous studies will come out of this? or perhaps some totally new discovery?!

GG

PS I just don't have much faith in gov't, read my signature! That's why I donate, nothing like our gov'ts can spend, but many people behind a cause can really help our situation!

 

[Simon]

Here are the full details from the NIH. [heavily formatted by me for clarity and emphasis]

Herpesviruses get top billing, which slightly surprises me. Overall, it looks like a good-sized cohort with follow-up and emphasis on changes during deterioration, which should be very interesting. It also includes MS paitents as 'sick' controls, which should help establish some specificity of any finding to ME/CFS. Previously this group has used both Fukuda and Canadian criteria (classifying each patient on both).

A LONGITUDINAL IMMUNOLOGICAL AND VIROLOGICAL STUDY FOR ME CFS BIOMARKER DISCOVERY

Abstract

DESCRIPTION:
A longitudinal study will be conducted of clinical presentation, immune phenotype, gene expression and virus infection among ME/CFS patients and MS and population controls frequency-matched by geographical area of residence, age-group (within 5 years), and sex.

Clinical samples will be collected fo:

• studies of NK cell function, virology (herpesvirus infection), and gene expression
• banking as a resource for future ME/CFS research.

Hypothesis:
ME/CFS is associated with immune dysfunction, which results from - or predisposes to - herpesvirus infections. Immune dysfunction will present as alterations in NK cell function that may lead to, or result from, alterations in cytokine production and altere expression of diverse immune-associated genes.

Finally, we predict that the ME/CFS immune phenotype may fluctuate over time and in association with clinical presentation and that the majority of patients clinically characterized as having ME/CFS will show a biosignature distinct from that of controls, and that further alterations will be seen during episodes of clinical exacerbation.

Activities and objectives:

1. Collect clinical and other data and venous blood samples at baseline and 6 months or at another time during the 6-month follow-up period when there is a perceived "significant" deterioration in symptoms
2. Analyze blood samples for NK cell phenotype and function
3. Screen samples for evidence of herpesvirus infection and viral load, focusing on Epstein Barr virus (EBV), cytomegalovirus (CMV), and human herpesvirus-6 (HHV-6)
4. Describe clinical phenotype and fluctuations over time
5. Correlate the presence of symptoms and severity with markers of virus activity and immune function
6. Investigate gene expression profiles associated with ME/CFS and how they vary in relation to changes in disease severity, virus activity, NK cell function, and other markers of immune function;
7. Securely store blood samples from patients and controls, anonymously linked to clinical and other data, as an open resource for researchers to conduct ethically-approved studies of ME/CFS.

Recruitment:

• 150 ME/CFS cases (50 severe, 100 non-severe), 75 MS controls, and 75 healthy controls will be recruited.
• For immunology and virology, 100 cases, 50 MS controls, and 50 healthy controls will be sampled at 2 time points.
• For gene expression, we will analyze 50 ME/CFS cases, 25 MS and 25 healthy controls, each at recruitment and one follow-up.

Cases will be selected from UK ME/CFS Disease Register and NHS ME/CFS specialty and primary care services in London and Norfolk, Suffolk, and Great Yarmouth and Waveney, UK; MS controls via the NHS; and healthy controls will be identified by ME/CFS patients (excluding blood relatives) or GPs.

Outcomes:
Identification of putative biomarkers for diagnosis, severity, and prognosis of ME/CFS, which can be evaluated in larger (ideally prospective) future studies.

In the long term, identification of robust biomarkers will allow clinicians to correlate ME/CFS phenotype (including clinical presentation, genetic, immune, and viral markers) with disease severity and prognosis and may reveal new options for interventions research.

PUBLIC HEALTH RELEVANCE:
This is, to our knowledge, the first longitudinal study of ME/CFS to incorporate both mild and severe cases, age, sex, and residence-matched Multiple Sclerosis (MS) and healthy controls, and to incorporate virological, immunological and gene expression data into the same study. There is a clear need for research in these areas, and the inclusion of severe cases using home visits will allow for research on a subset of patients often neglected in ME/CFS studies.

Because approximately 1-4 million Americans have ME/CFS, this study has the potential to impact the lives of a large patient population in the US as well as advance the state of the field in the US, UK, and globally through the potential identification of evidence related to disease etiology and pathophysiology as well as disease subtypes and biomarkers, revealing potential routes for treatment.

Good luck with the article Firestormm, there is certainly plenty of meat here to go on.

 

[Firestormm]

Simon There is certainly a lot in this and 'plenty of meat' as you say. Am doing plenty of digging this morning, through the layers beneath the original ME Observatory. Sure hope I can do it all justice

Interesting that, 'healthy controls will be identified by ME/CFS patients (excluding blood relatives) or GPs'. I haven't come across that method of selection before - have you?

I mean (my interpretation) ME patients choose the controls from people they know. Sounds 'odd' but need to think about it some more. Maybe it is a good idea in that I (as someone with ME if selected for the study) would be more inclined to choose someone who I thought couldn't possibly have ME. Unless I have misunderstood this? Entirely possible that I have

Thanks for laying it out so neatly. It was a lot of text to read. Saves me another job

Edit: I see the MEA have followed your example now Simon

 

[Bob]

Herpesviruses get top billing, which slightly surprises me.

That surprised me as well. I find that bit of the study a bit disheartening. I thought Herpes virus had been done to death. Unless they're using a novel virus-hunting technique, and they've got good reason to suspect that their technique will give new and meaningful results, and they're seeking to define herpes-related subsets, then it seems a bit futile. Am I missing something?

 

[MeSci]

That surprised me as well. I find that bit of the study a bit disheartening. I thought Herpes virus had been done to death. Unless they're using a novel virus-hunting technique, and they've got good reason to suspect that their technique will give new and meaningful results, and they're seeking to define herpes-related subsets, then it seems a bit futile. Am I missing something?

I have long suspected the involvement of herpes zoster/varicella zoster in my illness. A major reason is that at age 5 I had a severe case of chicken pox, and in the same year developed a unilateral facial nerve paralysis/palsy. It was not known what caused this (it was referred to as Bell's Palsy), but subsequent reading has led me to Ramsay Hunt syndrome, which is due to an infection of facial nerves by herpes zoster - see here:

http://www.patient.co.uk/doctor/facial-nerve-palsy

I hope they will be including herpes zoster in this research, which looks very promising.

 

[Firestormm]

That surprised me as well. I find that bit of the study a bit disheartening. I thought Herpes virus had been done to death. Unless they're using a novel virus-hunting technique, and they've got good reason to suspect that their technique will give new and meaningful results, and they're seeking to define herpes-related subsets, then it seems a bit futile. Am I missing something?

I think it is hard to tell from this hypothesis to what extent they will look at herpes-viruses per se. Rather I read it as saying, they are focusing on immune-system dysfunction. What they are looking at could be provoked by any viral trigger really couldn't it? Important thing for me is to see if immune dysfunction is observably significant in 'us' compared to the controls. I don't know where this herpes-virus theory comes from/what it is based on. Perhaps I can ask. Will have to see.

Incidentally, I haven't reposted here everything that Charles has been saying on Facebook, Bob. There was simply too much. Might help to have a read, might not. All developing.

 

[Sasha]

Me too, that's not even a Million pounds, right?

Oops, just read you properly! £1 is one pound, so yes, it's a million pounds - or $1.5 million.

 

[Bob]

I think it is hard to tell from this hypothesis to what extent they will look at herpes-viruses per se. Rather I read it as saying, they are focusing on immune-system dysfunction. What they are looking at could be provoked by any viral trigger really couldn't it? Important thing for me is to see if immune dysfunction is observably significant in 'us' compared to the controls. I don't know where this herpes-virus theory comes from/what it is based on. Perhaps I can ask. Will have to see.

Incidentally, I haven't reposted here everything that Charles has been saying on Facebook, Bob. There was simply too much. Might help to have a read, might not. All developing.

Thanks Firestormm. That had crossed my mind as well. In the CFSAC videos that I've been watching, the NIH representative said that when considering a grant application, they need to see a good hypothesis in the grant application. So perhaps the Herpes virus was easy to include to make their hypothesis complete. (i.e. an immune onslaught, or immune dysfunction, potentially triggered or caused by ongoing viral activity.) Perhaps the specific reference to herpes virus is a bit of a red herring and the rest of the study is more significant. Like you say, it's more a study of the immune system, rather than a study of Herpes virus.

 

[Bob]

I have long suspected the involvement of herpes zoster/varicella zoster in my illness. A major reason is that at age 5 I had a severe case of chicken pox, and in the same year developed a unilateral facial nerve paralysis/palsy. It was not known what caused this (it was referred to as Bell's Palsy), but subsequent reading has led me to Ramsay Hunt syndrome, which is due to an infection of facial nerves by herpes zoster - see here:

http://www.patient.co.uk/doctor/facial-nerve-palsy

I hope they will be including herpes zoster in this research, which looks very promising.

Oh, that's interesting. I didn't know that Chicken Pox and Shingles is a herpes virus (HHV-3) (Varicella zoster virus):
http://en.wikipedia.org/wiki/Herpesviridae#Human_herpesvirus_infections

Charles Shepherd got ill after contracting Chicken Pox from one of his patients.

I got ill just a few weeks after getting my first ever cold sore. (HHV-1 & HHV-2)

But past studies have not found consistent evidence of herpes virus involvement.

 

[Bob]

Interesting that, 'healthy controls will be identified by ME/CFS patients (excluding blood relatives) or GPs'. I haven't come across that method of selection before - have you?

I mean (my interpretation) ME patients choose the controls from people they know. Sounds 'odd' but need to think about it some more. Maybe it is a good idea in that I (as someone with ME if selected for the study) would be more inclined to choose someone who I thought couldn't possibly have ME. Unless I have misunderstood this? Entirely possible that I have

I'm no expert but this seems like it might be a good way to select healthy controls. Ideally, controls should be matched to the treatment group as closely as possible. (e.g. matched for location, age, gender, lifestyle etc.) This reduces external variables from the research as much as possible, so that the focus can be on significant/meaningful variables. If a patient nominates a control (e.g. a healthy friend), it is quite likely they would be a similar age, live nearby, and possibly even have a similar lifestyle. (The nominated control might even be a friend who lives in the same house as the patient, in which case the control might be location, age, lifestyle and gender matched.) So this reduces variables in the study. That's my basic understanding of the issue.

 

[Bob]

Incidentally, I haven't reposted here everything that Charles has been saying on Facebook, Bob. There was simply too much. Might help to have a read, might not. All developing.

Here are direct links to the MEA facebook discussions, in case helpful for anyone:
https://www.facebook.com/permalink.php?story_fbid=538192039571792&id=171411469583186
https://www.facebook.com/permalink.php?story_fbid=539415099449486&id=171411469583186

 

[MeSci]

I think it is hard to tell from this hypothesis to what extent they will look at herpes-viruses per se. Rather I read it as saying, they are focusing on immune-system dysfunction. What they are looking at could be provoked by any viral trigger really couldn't it? Important thing for me is to see if immune dysfunction is observably significant in 'us' compared to the controls. I don't know where this herpes-virus theory comes from/what it is based on. Perhaps I can ask. Will have to see.

Incidentally, I haven't reposted here everything that Charles has been saying on Facebook, Bob. There was simply too much. Might help to have a read, might not. All developing.

I agree that there is a wide range of potential triggers for ME, and am not (yet) convinced that it has to include a virus. If the leaky gut hypothesis is correct, for example, it could be chemicals, vaccines, chronic stress, surgery or other physical trauma, foods, medications, bacteria, etc,. that damage the gut mucosa and permit entry to the bloodstream of substances that set an abnormal immune process in train.

A quick internet search found several references to ME/CFS and HHV-6 including this page:

http://hhv-6foundation.org/associated-conditions/hhv-6-and-chronic-fatigue-syndrome

 

[MeSci]

Oh, that's interesting. I didn't know that Chicken Pox and Shingles is a herpes virus (HHV-3) (Varicella zoster virus):
http://en.wikipedia.org/wiki/Herpesviridae#Human_herpesvirus_infections

Charles Shepherd got ill after contracting Chicken Pox from one of his patients.

I got ill just a few weeks after getting my first ever cold sore. (HHV-1 & HHV-2)

But past studies have not found consistent evidence of herpes virus involvement.

Interesting about Charles Shepherd. Cold sores are caused by a different herpes virus - herpes simplex, usually HSV-1. I think I may have that one lurking too, as I now sometimes get things that look like cold sores for a few days, often coinciding with toothache and/or general mild flu-like malaise. I'm hoping it's a sign that my overactive immune system is calming down and not fighting everything! (How about that for a positive attitude?! Oh, and I haven't been doing a lot of kissing, unless you count my cats!)

 

[Firestormm]

Bob Thanks I hadn't pursued that line of thought - about commonality of location, etc. etc. Good points all.

Bob and MeSci I don't any longer get hung up on triggers or possible triggers personally. I (largely) think it's a dead end. I think we are looking more now at 'downstream' effects, if you will. And whatever the trigger actually was, I think it reasonable to operate on a theory that the immune system is screwed. Anyway, if this works out, they can always backtrack. Important for me that they establish 'something' of significance that separates the ME-pool or a proportion of them from the controls. Give me something I can 'hang my hat on'. It's all I really want now

 

[Bob]

I'm hoping it's a sign that my overactive immune system is calming down and not fighting everything! (How about that for a positive attitude?! Oh, and I haven't been doing a lot of kissing, unless you count my cats!)

We have to hope, don't we!
And I'm not surprised you kiss your ginger cat! He looks lovely! meow.

 

[MeSci]

I'm not surprised you kiss your ginger cat! He looks lovely! meow.

She is!

 

[Simon]

That surprised me as well. I find that bit of the study a bit disheartening. I thought Herpes virus had been done to death. Unless they're using a novel virus-hunting technique, and they've got good reason to suspect that their technique will give new and meaningful results, and they're seeking to define herpes-related subsets, then it seems a bit futile. Am I missing something?

They may be extremely interested in the Herpesvirus connection. It's just possible, though, that focusing on Herpesvirus increased their chance of funding from the NIH . The press release from LSTH emphasised the more general biobank role, as did PR from the UK charities involved.

SimonInteresting that, 'healthy controls will be identified by ME/CFS patients (excluding blood relatives) or GPs'. I haven't come across that method of selection before - have you?

I mean (my interpretation) ME patients choose the controls from people they know. Sounds 'odd' but need to think about it some more. Maybe it is a good idea in that I (as someone with ME if selected for the study) would be more inclined to choose someone who I thought couldn't possibly have ME. Unless I have misunderstood this? Entirely possible that I have

I'm no expert but this seems like it might be a good way to select healthy controls. Ideally, controls should be matched to the treatment group as closely as possible. (e.g. matched for location, age, gender, lifestyle etc.) This reduces external variables from the research as much as possible, so that the focus can be on significant/meaningful variables. If a patient nominates a control (e.g. a healthy friend), it is quite likely they would be a similar age, live nearby, and possibly even have a similar lifestyle. (The nominated control might even be a friend who lives in the same house as the patient, in which case the control might be location, age, lifestyle and gender matched.) So this reduces variables in the study. That's my basic understanding of the issue.

Have to admit I'm a bit concerned by this too, and it's not an ideal way of recruiting controls.

Also note they are age matching on frequency not case. This means they will have, say, the same proportion of controls aged 30-35 as CFS cased aged 30-35. In Mady Hornig's pathogen study (and the XMRV study), they carefully matched individual cases, eg a female aged 30-35 CFS patient would be matched to a female control aged 30-35 (they also matched on location too). Studying immune parameter eg NK cell function and cytokines is notoriously difficult because there is so much natural variation in both healthy people and in patients. Carefully controlling for age, sex etc helps to reduce the variation and increases the chance of robust results (and of finding any real differences).

One person on this forum said she met the CFS criteria for the pathogen study but didn't know yet if she would be in the final study because it depended on them finding a suitably matched control. Such attention to detail is laborious and no doubt expensive too but is a better way to do things if possible. though using the patient/GP selection method should match well on location.

 

[Bob]

Bob and MeSci I don't any longer get hung up on triggers or possible triggers personally. I (largely) think it's a dead end. I think we are looking more now at 'downstream' effects, if you will. And whatever the trigger actually was, I think it reasonable to operate on a theory that the immune system is screwed. Anyway, if this works out, they can always backtrack. Important for me that they establish 'something' of significance that separates the ME-pool or a proportion of them from the controls. Give me something I can 'hang my hat on'. It's all I really want now

Yep, I agree with your thinking. But if there is any virus, then I'm hoping that the (very large and complex) Hornig/Lipkin study will find it.