XMRV Retrovirus: Round up 25: WPI on DeFreitas, Hansard, MEA, AfME, Johnson

XMRV Retrovirus: Round up 25: WPI DeFreitas statement, Hansard, MEA, Action for M.E., Hillary Johnson blog

WordPress Shortlink: http://wp.me/p5foE-2tq

XMRV Retrovirus: Round up 24: Testing and news of research studies click  here: http://wp.me/p5foE-2sX

Click here for all previous XMRV Round ups and XMRV related postings in reverse date order

Whittemore Peterson Institute on Facebook

Statement posted by Whittemore Peterson Institute on 25 November under their “Notes” tab

http://tinyurl.com/WPIFacebook8  

Fact #8

Wednesday, November 25, 2009 at 8:44pm

XMRV is Not the retrovirus identified by De Freitas et al.

the publication and patent submitted by De Freitas et all clear describe the molecular characteristics of a retrovirus that is not a gamma (type C) retrovirus. The patent submitted for the retroviruses states

“Chronic Fatigue Immunodeficiency Syndrome associated virus, hereafter referred to by the name CAV may be morphologically characterized as a retrovirus, particularly a non-C retrovirus which is capable of infecting humans. Electron microscopy of viral particles formed in infected human cell cultures suggests that CAV is a non-C type retrovirus because of its diameter, morphology, formation and location of intracellular virions. The Electon micrographs of XMRV shown in Lombardi et al clearly depict a budding type C retrovirus of 90-100microns The DeFritas patent goes on to say “More specifically, CAV-infected cells could be characterized by electron-dense circular virions, some with electron-luscent cores and others with electron-dense cores, associated with the rough endoplasmic reticulum and inside large abnormally distended mitochondria in the cells. All particles are the same shape and size, 46-50 nm. No extracellular virus is observed. No forms budding from the cytoplasmic membranes are observed.

Thus, CAV-infected cells could also be charcterized by the presence of intracytoplasmic particles”Gamma (type C) retroviruses are 90 1100uM as shown in Lombardi et al and all are shown to consist of electron dense cores and specifically to bud extra-cellularly not intracellularly.

The data describes in the Defreitas patent can be found at:

http://www.ncf-net.org/forum/revelations.html

These data are indisputable that XMRV is NOT the retrovirus described by De Freitas et al.”

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Hansard

http://www.publications.parliament.uk/pa/cm200910/cmhansrd/cm091207/text/91207w0010.htm

7 Dec 2009 : Column 46W

Biomedical Research

Paul Rowen: To ask the Minister of State, Department for Business, Innovation and Skills what biomedical research into myalgic encephalomyelitis and xenotropic murine leukaemia virus-related virus is being undertaken. [304330]

Mr. Lammy: The Medical Research Council (MRC) is one of the main agencies through which the Government support medical and clinical research. The MRC is an independent body which receives its grant in aid from the Department for Business, Innovation and Skills.

In 2008-09 the MRC’s total expenditure for research relating to Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) amounted to £728,000. This supported four projects including a £164,000 research programme led by Dr. C Clark at Queen Mary College, London on the general and specific risk markers and preventive factors for chronic fatigue and irritable bowel syndromes. CFS/ME continues to be a strategic priority area for funding and the MRC remains committed to supporting scientific research into all aspects of CFS/ME including evaluations of treatments and studies into the biological basis of the condition.

The MRC recently held a CFS/ME research workshop where the recent xenotropic murine leukaemia virus-related virus (XMRV) findings were among the items discussed. A note of the discussions will be published on the MRC website in due course.

The MRC’s National Institute for Medical Research are leading a programme on infection and replication of retroviruses (including XMRV). One study within the programme is looking at how XMRV reproduces in the cell, its interaction with host cell factors and how it subverts the host immune systems.

© Lord Hansard

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ME Association

Response from Dr Charles Shepherd to concerns from member of the ME community:

Neil [Riley, Chair MEA Board of Trustees] has asked if I could respond to your email to the MEA about patient selection in XMRV research that might be funded by the RRF.

This is a complex issue and I’ve tried to explain the situation in rather more detail in version 4 of the MEA position statement, which is now up on the MEA website: www.meassociation.org.uk

Very simply, we are looking at a two stage research situation that will hopefully clarify the situation regarding XMRV prevalence in the ME/CFS population at some point in 2010, and (depending on the results) then move on to looking at viral pathogenicity in more detail (ie is this a disease causing virus?) and antiviral treatment. Incidentally, the results of a new research study looking at the use of AZT as a possible treatment for XMRV will be up on the MEA website later today: www.meassociation.org.uk .

As you know, the WPI study used patients who met both Fukuda research criteria and Canadian clinical criteria – partly because scientific journals don’t accept the validity of the CCC as a valid research tool..

Not surprisingly, the first stage of the attempt to replicate these results has resulted in various international groups almost entering a race to see who could replicate or refute the WPI results first. And this has meant they have gone for an easy and immediate source of patient material >> stored blood samples. I am not aware of any stored blood samples here in the UK that are from patients who meet Fukuda plus Canadian criteria and I doubt if there are any. So there was no point in the MEA insisting that research funding in stage one could only be used in studies involving Canadian criteria patients, or CC + Fukuda.. I therefore suggested that these ‘first off the mark’ studies should only involve Fukuda criteria patients as here in the UK there is a real worry that retrovirologists, who have very little general knowledge of ME/CFS, might be using samples from patients from NHS sources that meet either Oxford research or even NICE clinical criteria – the latter being used by the NHS clinics. It would have been helpful if the paper itself had carefuly specified the selection criteria because I know that there are researchers taking this forward on the basis that CFS in the paper = CFS Fukuda.

As far as the second stage is concerned, we would certainly be looking at funding a study that would use Fukuda plus Canadian criteria but there are still going to be major problems and we cannot be dogmatic here. This is because the NHS services do not use Canadian criteria in their clinical assessments and most of us who work in the UK private sector don’t have sufficient numbers of new patients coming through to quickly build up a decent number (ie 100 cases) meeting both criteria, and we don’t tend to be dogmatic about the use of criteria in patients already diagnosed.

And this may be why MERUK has decided to fund a study in Sweden rather than here in the UK. The MEA would prefer to fund UK XMRV studies but we are willing to look at overseas proposals – as has already happened.

As you will have seen I have spent a great deal of time over the past few weeks talking to virtually all the virologists and retrovirologists here in the UK that are interested in taking this work forward, and the MEA is very keen to help in whatever way we can. I hope the researchers are now well aware of the issues surrounding careful patient selection (some of them were definitely not) and not just the science behind XMRV.

I hope you find this helpful.

I would be happy to discuss in more detail if you would like to call me on my home number when convenient.

Regards

Dr Charles Shepherd
Hon Medical Adviser, MEA

(This information may be forwarded if you wish to do so)

ME Association

XMRV and ME/CFS? What do we know so far? And what don’t we know? (version 4)

27  November 2009

Version 4 of the MEA position statement on XMRV clarifies some of the points and queries raised in the previous three summaries. Version 4 also updates the situation on XMRV research in the UK, testing for XMRV, and refers to our correspondence with the Chief Medical Officer regarding blood supplies and blood donation.

This summary is intended to be a balanced account of the current situation. It therefore not only raises questions but is also very cautious when it comes to drawing any firm conclusions about the role of XMRV in ME/CFS as either a diagnostic marker, causative agent, or abnormality that requires active treatment with antiviral medication.

[...]

ROLE OF ME RESEARCH UK (MERUK) and IRISH ME TRUST

MERUK and The Irish ME Trust have just announced that they are providing joint funding for a replication study that will be carried out in Sweden. This work will be carried out by Professor Blomberg, Head of the Research Group of Clinical Virology, University of Uppsala and Professor Gottfries, from the Sahgrenska University Hospital, Molndal. The researchers will retrospectively test previously stored samples from 3 groups of patients (20 Fukuda defined ME/CFS; 20 fibromyalgia; 20 irritable bowel) and 20 controls. In addition, they will prospectively test samples from 120 ME/CFS patients defined by Fukuda 1994 and Canadian 2003 clinical criteria. Results are expected in Spring/Summer 2010. More information on this study can be found on the MERUK website.

http://www.meresearch.org.uk/research/projects/xmrvsweden.html

SELECTING PEOPLE FOR FURTHER RESEARCH STUDIES

There is clearly an immediate need for international agreement and co-operation on the research criteria being used to select well-characterised ME/CFS patients for further research into XMRV. Otherwise, we could end up in spring/summer 2010 with a collection of conflicting results on prevalence because different international research groups have been using different patient selection criteria.

In the present situation, many research groups are reluctant or unwilling to use Canadian criteria. This is because these are essentially clinical criteria and in the eyes of many researchers they have not been validated for use in research studies as stand alone criteria. There is also the problem in that most research groups do not having ready access to stored blood samples from ME/CFS patients that meet Canadian criteria.

So the best way forward may be for everyone to agree to use either Fukuda-defined CFS – which would obviously help to define which sub-groups of patients are XMRV positive under this CFS umbrella – or, if possible, to use patients that meet both Fukuda CFS and Canadian clinical criteria. It is worth noting that a significant proportion of people with Ramsay-described ME will not meet Fukuda criteria for CFS – so they are likely to be excluded from research currently taking place.

We do not believe that it is sensible to extend the entry criteria into research studies by using the 2005 ‘empirical’ definition of CFS for patient selection purposes as this will bring in an even more diverse group of patients who have chronic fatigue. This point has also been made by Dr Nancy Klimas when she addressed the CFSAC meeting in Washington in October.

Provided there is careful selection of ME/CFS patients, healthy controls and disease controls, we may then be able to draw some meaningful conclusions about which people who come under the wide clinical spectrum of CFS clinical presentation have XMRV and which do not.

Besides using stored blood samples, research needs to involve fresh clinical cases, as well as other disease groups (particularly inflammatory conditions with immune activation) and properly matched healthy controls.

Click for full version 4 here

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Action for M.E.  

http://www.afme.org.uk

Professor Tony Pinching, Action for M.E.’s Principal Medical Adviser, sets out his views on XMRV in this article from InterAction 70, published this week:

InterAction 70 Christmas 2009

Page 9

Potential virus breakthrough

We thought all our Christmases had come early in October, when researchers at the Whittemore Peterson Institute in Reno, USA announced that they had identified genetic material (DNA) from a mouse virus – murine leukaemia virus related virus or XMRV- in 68 out of 101 CFS patients (67%) compared to 8 out of 218 (3.7%) of healthy people.

Further blood tests showed that more than 95% of CFS patients have antibodies to XMRV, indicating they had been infected with the virus, which may then have lain dormant in their DNA.

Dr Judy Mikovits, research director, Whittemore Peterson Institute, is testing a further 500 blood samples collated from patients diagnosed with CFS in London.

In our press statement, quoted in part by the BBC, Sir Peter Spencer said:

“It is still early days so we are trying not to get too excited but this news is bound to raise high hopes among a large patient group that has been ignored for far too long.

“If the researchers can go on to prove a definitive cause and effect between this retrovirus and M.E., it will make an enormous difference to 250,000 men, women and children who have M.E. in this country.

“Action for M.E. has long been calling on the UK Government to invest more in research into the causes of this horrible illness. Once we know the cause, researchers can start working on more effective treatments, preventive measures and ultimately a cure for M.E.”

What does this research signify?

Professor Tony Pinching, Action for M.E.’s Principal Medical Adviser says the study needs to be confirmed by independent research and it would be very premature to think about clinical tests or treatments based on these early findings (see below). His caution is echoed in statements by Professor Andrew Lloyd, Director, Centre for Infection and Inflammation Research, University of New South Wales (see www.me-cfs.org.au/node/448 ), NCI director Dr John Niederhuber (www.cfids.org/temp/xmrv-guidelines-nci.asp ) and Dr Charles Shepherd, ME Association www.meassociation.org.uk  (under ‘quick links’ on their home page). Professor Pinching comments:

“A new research report about CFS in a major science journal is obviously reason for some excitement. Many of you will have heard the news reports – some will have been hopeful, others sceptical, and many others unsure what to think. And that’s about the size of it too for the informed observer of the scientific data.

“In essence, a US study has shown apparent evidence of a virus (XMRV) in the blood cells of people with CFS, taken from a repository of samples from ‘well-characterised cohorts of patients.’

“XMRV is related to a class of mouse leukaemia viruses that have not been previously firmly associated with any human disease, although recently seen in some patients with prostate cancer. Although these viruses have been much studied in cancer biology, they can also be contaminants, although circumstantial evidence is against this here.

“67% of CFS patients compared with 4% of controls showed evidence of the DNA of this virus. Other evidence shows that the virus is actively expressed in patient cells, is capable of passing from cell to cell, and generates a detectable immune response in patients.

“The brief report lacks information about patient characteristics, and the comparability of patient and control samples, but the data seem plausible and internally consistent.

“However, much more work is needed to determine what these early findings signify. The first and most crucial test would be independent verification, through studies on large numbers of carefully characterised patients at other sites, preferably on fresh, not stored, samples.

“We also need studies on large numbers of both healthy people and people with other conditions. This is to clarify how specific the association is, and the extent to which XMRV occurs in other chronic immunological or neurological conditions.

“Biologically, there is no obvious mechanism that would link this sort of virus (very different from familiar viruses) to this sort of condition, although various plausible hypotheses could be devised. Most importantly, the virus could as easily be an effect of the illness, as it could be a cause or disease mechanism. An altered state of immune cells – from which the virus was derived – could activate an innocent passenger virus, for example.

“For the usual reasons, very preliminary research results have led to much speculation, inevitably raising hopes of people with CFS/ME. Loose talk of clinical tests and therapies based on these findings may reflect a genuine need for such things, but not any clear justification from the published science to date.

“So my thoughts so far are:

. this is interesting, but it first needs independent and substantive confirmation

. we don’t know whether XMRV is cause, effect, or just a passenger

. it would be very premature to think about clinical tests or treatments based on these early findings

. perhaps the most important thing is that this work will foster more high quality research on the biology of this clinically important but scientifically enigmatic condition.”

Professor Tony Pinching, for Action for M.E.  InterAction 70 Christmas 2009

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Commentary on research

Dr. Timothy Luckett’s blog

http://cfidsresearch.blogspot.com/

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Hillary Johnson (journalist and author of Osler’s Web)

13 November 2009

“I’ve written a new blog post about the recent CFSAC meeting in Washington, D.C. and the new scientific terrain created by the discovery of XMRV.”

http://www.oslersweb.com/blog.htm?post=646449

5 December 2009

“When did it stop being about you and become all about them?”

http://www.oslersweb.com/blog.htm?post=648635

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Websites, communities, commentary and quality forums

Dan Moricoli’s ME-CFS Community

http://cfsknowledgecenter.ning.com/profiles/blog/list

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Cort Johnson’s Phoenix Rising website: http://aboutmecfs.org/Rsrcs/XMRVResources.aspx

Cort Johnson’s Blog and comments: http://aboutmecfs.org/blog/

Cort Johnson’s Forums: http://forums.aboutmecfs.org/

Link Back

Whittemore Peterson Institute on Facebook

For initial Whittemore Peterson Press Release, NIH (National Institutes of Health) News Release, go here: http://wp.me/p5foE-272

For PDF reprint of Science paper go here:

http://www.sciencemag.org/cgi/rapidpdf/1179052?ijkey=m3wzKT4yJqEyk&keytype=ref&siteid=sci

Click here for all previous XMRV Round ups and postings in reverse date order: http://meagenda.wordpress.com/category/xmrv/

XMRV Retrovirus: Round up 24: Testing and news of research studies

XMRV Retrovirus: Round up 24: Testing and news of research studies

WordPress Shortlink: http://wp.me/p5foE-2sX

Click here for all previous XMRV Round ups and XMRV related postings in reverse date order

Testing for patients in the US

Whittemore Peterson Institute for Neuro Immune Disease: http://www.wpinstitute.org/

WPI Announces Availability of XMRV Testing

Press release: http://www.wpinstitute.org/WPI%20Release%20Diagnostic%20Test.pdf

VIP Diagnostics (VipDX): http://www.vipdx.com/

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Report from CFIDS Association of America

From the December edition of the CFIDS Association of America’s CFIDSLink e-newsletter:

HHS Coordinating Xenotropic Murine Leukemia Virus-Related Virus (XMRV) Scientific Activities

The U.S. Department of Health and Human Services (HHS) has formed an interagency scientific working group on XMRV. The Blood XMRV Scientific Research Working Group will report to the Department’s Blood, Organ and Tissue Senior Executive Council through established mechanisms. No formal statement has been issued yet, but the working group includes representatives from the DHHS Office of Public Health and Science, the National Institutes of Health (NIH), the Centers for Disease Control and Prevention (CDC) and the Food and Drug Administration (FDA). The working group will have scientific responsibilities for investigation of XMRV as it relates to blood supply and CFS. Suzanne D. Vernon, PhD, the CFIDS Association’s scientific director, has been asked to participate in the XMRV scientific working group.

Dr. Jerry Holmberg of the HHS Office of Public Health and Science made a brief presentation on Oct. 30, 2009 to the DHHS CFS Advisory Committee. He described the existing response systems that address threats to blood safety, such as new and emerging infectious agents like XMRV. The HHS Blood XMRV Scientific Research Working Group will chaired by a representative of the NIH’s National Heart, Lung and Blood Institute (NHLBI) and will collaborate closely with the agencies in charge of these systems, including the NHLBI’s Retrovirus Epidemiology Donor Study (REDS). REDS was created in 1989 to address risks associated with HIV-1, HIV-2, HTLV-1 and HTLV-2 in the general blood supply.

In more recent communications with Dr. Holmberg, he stated that the Blood XMRV Scientific Research Working Group is taking a three-stage approach to its handling of the issues related to XMRV and the possible link to human disease. The first stage will be to standardize and validate laboratory methods and reagents for XMRV testing. This is important since variations in sample collection and laboratory procedures can produce discrepant results. These standardized approaches will be used initially to test 1,200 healthy donors’ blood samples and 100 CFS patients’ blood samples collected by Dr. Judy Mikovits of the Whittemore Peterson Institute. Stage two will assess the prevalence of XMRV in the general population and blood supply, as well as in other CFS patient cohorts. The third stage will be a series of studies to understand how XMRV is transmitted, whether it causes human disease, and how it affects various subgroups of the population.

The immediate focus is to ascertain any risks to the general blood supply that XMRV might pose, but the scientific working group is also addressing validation studies for diagnostic tests and if necessary, potential blood screening tests. If the studies indicate that screening is required for blood products, blood screening test, must be submitted to and approved by the FDA before they can be marketed. Neither of the tests currently being offered by two commercial labs has been reviewed by the FDA.

According to CDC, their studies using samples obtained from the Whittemore Peterson Institute has HHS attention. The Laboratory Branch in CDC’s Division of HIV/AIDS Prevention is doing the XMRV testing and not the CDC CFS research group in the Division of Viral and Rickettsial Diseases.

Representatives from the FDA attended the XMRV meeting sponsored by Abbott Laboratories at Cleveland Clinic on Nov. 11, 2009. Dr. Robert Silverman of the Cleveland Clinic gave a seminar about XMRV for HHS staff on Dec. 2, 2009.

Dr. Holmberg emphasizes the need for careful application of scientific methods to ensure that these studies are conducted with exceptionally high rigor and reliability so that the results provide a solid scientific foundation for moving forward. He understands the strong interest within the CFS patient community for swift action and definitive answers, and expressed the high priority that this subject is receiving within a broad range of functions within the Department of Health and Human Services.

The CFIDS Association will provide updates on these important activities as new information becomes available.

Links:
December edition of CFIDSLink:
http://www.cfids.org/archives/2006-2010-cfidslink/december-2009.asp

CFIDS Association’s XMRV Resources:
http://www.cfids.org/XMRV/default.asp#info

DHHS Statement on Blood Safety and Availability:
http://www.cfids.org/xmrv/blood-supply-ophs.pdf

NCI Q&A About XMRV:
http://www.cancer.gov/newscenter/pressreleases/XMRV_QandA

Summary of the October 2009 CFS Advisory Committee meeting:
http://www.cfids.org/cfidslink/2009/110401.asp

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Commentary

http://chronicfatigue.about.com/b/2009/11/26/chronic-fatigue-syndrome-news-xmrv-test-available-from-wpi.htm

By Adrienne Dellwo, About.com Guide to Fibromyalgia & CFS

Chronic Fatigue Syndrome News: XMRV Test Available From WPI

Thursday November 26, 2009

NEWSBRIEF: The Whittemore Peterson Institute (WPI) is now allowing a laboratory to temporarily offer the tests researchers used in the study linking XMRV to chronic fatigue syndrome (CFS or ME/CFS)…

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Testing for patients in the UK and Europe

http://www.xmrvtesting.co.uk/index.html

http://www.xmrvtesting.co.uk/UNITED_KINGDOM_XMRV_TESTING.htm

A member of the UK ME community is maintaining a site collating information on XMRV testing for patients in the UK and Europe.  (Note: I have no connection with this site and all enquiries should be directed to the site webmaster and not to ME agenda.)

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News of research studies

On 24 September, the Whittemore Peterson Institute announced news of a five year $1.6 million award

http://www.prohealth.com/library/showarticle.cfm?libid=14948  

NIH Bets $1.6 Million on Continued ME/CFS Research by Drs. Mikovits & Kerr
October 21, 2009

Dr. Judy Mikovits (principle investigator) and the Whittemore-Peterson Institute, with collaborator Dr. Jonathan Kerr, have been awarded a 5-year, $1.6 million grant from the NIH’s National Institute of Allergy and Infectious Diseases (NIAID) to support ongoing research into the disease mechanisms of chronic fatigue syndrome. Dr. Kerr is associated with St. George’s College in London.

The award was announced Sep 24 on the WPI website, before news of the CFS-associated XMRV retrovirus was published Oct 8 by the journal Science. A description of the project (# 1R01AI078234-01A2) is now included in the NIH’s Research Portfolio Online.

( http://projectreporter.nih.gov/reporter.cfm?CFID=7257406&CFTOKEN=97499939 )

Key Details from the NIH’s Project Description

• Title: “New Strategies to Decipher the Pathophysiology of Chronic Fatigue Syndrome.”

• Objective: “To provide significant insight into the disease mechanisms of Chronic Fatigue Syndrome so accurate testing and specific treatments can be developed with a goal of curing the disease and preventing life-threatening complications.”

• Timing: start date Sep 28, 2009; projected end date, Aug 31, 2014.

• Funding: First fiscal year funding $335,600; total funding $1.6 million.

• Project Description provided by applicant: (excerpt formatted for greater legibility, as follows).

______________________________

“Chronic Fatigue Syndrome (CFS) is a complex disease estimated to affect between 0.5%-2% of the population in the Western world.

Its pathogenesis is thought to involve both inherited and environmental (including viral) components, as with other chronic inflammatory diseases, such as multiple sclerosis, rheumatoid arthritis, and atherosclerosis.

Consistent with this chronic inflammatory context, CFS patients are known to have a shortened life-span and are at risk for developing lymphoma. We hypothesize that chronic inflammatory stimulation from active and recurrent infections of multiple viruses on a susceptible host genetic background leads to the pathogenesis characterized by CFS.

The overall goal of this research project is to define these viral and host parameters in European and American cohorts of CFS patients that correlate with distinct disease phenotypes, including the development of mantle cell lymphoma (MCL) in a subgroup of the American cohort.

In Aim 1) we will identify and confirm novel viral infections in European and American CFS patient cohorts.

1.1) We will use two complementary methods for detection of novel virus mRNA: massive parallel signature sequencing (MPSS) and a custom DNA microarray.

1.2) Quantitative polymerase chain reaction Q-PCR will be used for confirmation of virus gene expression.

1.3) Immortalized cell lines will be developed to isolate virus and elucidate links between virus and host cell gene expression.

In Aim 2), we will elucidate genetic factors of susceptibility and the dysregulation of the host defense system. Specifically, we will determine:

2.1) PBMC gene expression of 88 human genes previously confirmed as being differentially expressed in CFS

2.2) Serum chemokine and cytokine profiles using multiplex suspension antibody arrays on a Luminex platform

2.3) HLA, KIR genotypes and whole genome SNP profiles

2.4) Defects in the type I Interferon signaling pathway.

In each subaim both cohorts will be compared to normal and disease controls using specimens of serum and PBMC taken at multiple time-points from individual patients and taken from our unique and extensive sample repository.

This study:

• Will provide information necessary for development of treatment and diagnostic strategies for distinct subgroups of CFS patients,

• And may identify novel virus associations, genetic signatures, and biomarkers, which can predict the development of MCL, thus enabling use of preventive therapeutics.”….

For WPI Research Studies and Clinical Trials go here: http://www.wpinstitute.org/xmrv/xmrv_trials.html

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Dr Jonathan Kerr and Dr Derek Enlander

It has been widely reported on forums that Dr Jonathan Kerr (St. George’s University, London) and Dr Derek Enlander (New York) are also engaged in XMRV replication studies.

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XMRV researchers

According to an unofficial summary published by Dr Charles Shepherd on behalf of the ME Association following the APPG on ME meeting on 2 December:

“XMRV was discussed in some detail at the Medical Research Council Expert Group Workshop on November 19/20 where there were four UK researchers present who are actively involved in XMRV research:

• Dr Jonathan Stoye – National Institute for Medical Research
• Dr Kate Bishop – NIMR
• Dr Jonathan Kerr – St George’s Hospital
• Dr Suzanne Hagan – Glasgow Caledonian University

There are several other UK virologists involved with XMRV research as well – including Prof Greg Towers at University College London, whom CS recently met for an afternoon discussion.

So replication studies and other XMRV research is taking place, or is about to take place, here in the UK.

MERUK plus IRISH ME TRUST has just funded an XMRV replication study in Sweden.

The MEA Ramsay Research Fund has money available for UK studies – but money does not appear to be an immediate problem in the UK.

It looks as though there may even be some early results from replication studies before the end of the year.”

—————

Update: FOI request for information pending

University College London PhD project

http://www.findaphd.com/search/showproject.asp?projectid=18971

Dept/School Division of Infection & Immunity, University College London
Project Supervisor(s) Prof G Towers

Dr P Kellam
Funding Availability Competition Funded Project (European/UK Students Only)

A role for XMRV in human disease

Laboratory supervisor: Prof Greg Towers

Clinical supervisor: Prof Deenan Pillay

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Swedish XMRV study

http://www.meresearch.org.uk/research/projects/xmrvsweden.html

Prof Jonas Blomberg (Clinical Virology, University of Uppsala) and Prof Carl-Gerhard Gottfries (Sahlgrenska University Hospital, and the Gottfries Clinic) have just begun exploration of the relationship between XMRV and ME/CFS, with funding provided by ME Research UK and the Irish ME Trust

The results of this replication study are exxpected to be available in the Spring/Summer of 2010.

Related material:

ME Research UK overview essay: XMRV and ME/CFS – A stunning find

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Commentary on XMRV research and updates on studies

Thread on Cort Johnson’s Forums: http://forums.aboutmecfs.org/showthread.php?t=1349

Dr. Timothy Luckett: http://cfidsresearch.blogspot.com/

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Commentary and quality forums

Cort Johnson’s Phoenix Rising website: http://aboutmecfs.org/Rsrcs/XMRVResources.aspx

Cort Johnson’s Blog and comments: http://aboutmecfs.org/blog/

Cort Johnson’s Forums: http://forums.aboutmecfs.org/

Link Back

Whittemore Peterson Institute on Facebook

For initial Whittemore Peterson Press Release, NIH (National Institutes of Health) News Release, go here: http://wp.me/p5foE-272

For PDF reprint of Science paper go here:

http://www.sciencemag.org/cgi/rapidpdf/1179052?ijkey=m3wzKT4yJqEyk&keytype=ref&siteid=sci

Click here for all previous XMRV Round ups and postings in reverse date order: http://meagenda.wordpress.com/category/xmrv/

The Role of Viruses in ME/CFS, XMRV and the MRC PACE Trial: Margaret Williams 21 November 2009

The Role of Viruses in ME/CFS, XMRV and the MRC PACE Trial – Margaret Williams – 21st November 2009

WordPress Shortlink: http://wp.me/p5foE-2qd

Permission to Repost

Note:  This is a long and heavily formated document and I am posting only the introduction here:

The full document can be accessed here on MEActionUK website:

http://www.meactionuk.org.uk/The-role-of-viruses-in-ME.htm

http://tinyurl.com/ykjveep

http://www.meactionuk.org.uk/The-role-of-viruses-in-ME.pdf

http://tinyurl.com/y8m8s8h

The role of viruses in ME/CFS: what, if any, will be the effect of the discovery linking XMRV to ME/CFS on the MRC PACE Trial?

by Margaret Williams

21 November 2009

For decades it has been known and shown that viruses play a role in ME/CFS; some illustrations from the literature are provided below (all of which are relevant and significant).

In relation to “CFS”, the most-studied viruses have been the Epstein-Barr Virus (EBV) and the Human Herpes Virus-6 (HHV-6). In relation to “pure” ME, the most studied viruses (and for which there is extensive evidence) have been the enteroviruses, usually Coxsackie B (CBV). Some illustrations from the literature of the role that viruses play in ME/CFS are provided at the end of this paper; all are significant.

There is increasing awareness that the dysregulated immune system that is a hall-mark of ME/CFS allows multiple latent viruses and microbial agents to become reactivated (Co-Cure NOT:12th November 2009).

Moreover, recent research has shown that even viruses which were hitherto believed not to persist after an acute infectious episode are capable of long-term viral persistence.

Nora Chapman et al from the Enterovirus Research Laboratory, Department of Pathology and Microbiology, University of Nebraska Medical Centre, have shown that human enteroviruses Coxsackie B can naturally delete sequence from the 5’ end of the RNA genome and that this deletional mechanism results in long-term viral persistence, which has substantially altered the previously held view

(http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2440640/?tool=pubmed ). In a specially commissioned piece for the charity Invest in ME, the researchers say: “This previously unknown and unsuspected aspect of enterovirus replication provides an explanation for reports of enteroviral RNA detected in diseased tissue in the apparent absence of virus particles” (Journal of IiME 2009:3:1).

Dr John Chia, an infectious diseases specialist from Torrance, California, who specialises in ME/CFS, is on record: “I believe that the main reason (ME)CFS patients are symptomatic is due to continuing inflammatory response toward viruses living within the cells, enteroviruses in most of the cases I see. We have clearly documented certain enterovirus infections triggering autoimmune responses in some patients…Can you imagine how we would feel if there are viruses surviving in our muscles, brains, hearts and gastrointestinal tracts triggering ongoing immune responses?”  
(http://aboutmecfs.org/blog/?p=865 ).

The CFIDS Chronicle (Research Update, Summer 1993) explained viruses and retroviruses as follows:

“A virus is a microscopic organism that lives within the cells of another living organism. Viruses cause disease at the most basic level, by damaging the cells of living things. By themselves, viruses are lifeless particles incapable of reproduction, but once they enter the cell of another living thing they become active organisms that can multiply hundreds of times.

“Viruses are comprised of two parts – a core of either deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) and a protective envelope of protein. RNA viruses are smaller than DNA viruses and sometimes contain a special enzyme called reverse transcriptase which allows them to convert RNA to DNA. These specialised viruses are known as retroviruses and have a unique ability to merge with the host’s own genetic material.

“Retroviruses have the unique ability to replicate themselves by (i) making a double-stranded DNA copy called a ‘pro-virus’ once they enter living cells. Pro-viruses integrate themselves into the human chromosome and become part of the host’s genetic code (ii) alter the host’s immune response by evading detection as a ‘hidden invader’ (iii) remain hidden and latent, spliced within the host’s DNA, for long periods of time. Retroviruses are known to be potent stimulators of cytokines”.

On 8th October 2009 the premier journal Science published a paper online showing a direct link between a retrovirus and ME/CFS (Detection of infectious retrovirus XMRV, in blood cells of patients with chronic fatigue syndrome. Lombardi VC, Ruscetti FW, Peterson DL, Silverman RH, Mikovits JA et al) which caused global reverberations.

However, this was not the first time that a retrovirus had been associated with ME/CFS.

In 1991, using polymerase chain reaction and in situ hybridisation, Dr Elaine De Freitas, a virologist at the Wistar Institute, Philadelphia (which is America’s oldest independent institution devoted to biological research) and Drs Daniel Peterson, Paul Cheney, David Bell et al found such an association (Retroviral sequences related to human T-lymphotropic virus type II in patients with chronic fatigue immune dysfunction syndrome. Proc Natl Acad Sci USA 1991:88:2922-2926). It is notable that co-author Hilary Koprowski is a distinguished virologist and Professor Laureate who was Director of the Wistar Institute from 1957-1991; he is a member of the US National Academy of Sciences and is Director of the Centre for Neurovirology at Thomas Jefferson University.

Before publication, the findings were presented on 4th September 1990 by Elaine De Freitas at the 11th International Congress of Neuropathology in Kyoto, Japan.

Ten days later, on 14th September 1990 Dr Peter White (as he then was) and other members of the Wessely School dismissed the findings: “in the vast majority of CFS cases there is a psychological component. About 75% of CFS sufferers are clinically depressed, according to Peter White, senior lecturer in the department of psychiatric medicine at St Bartholomew’s Hospital in London. White said he believes depression is often a cause, rather than a consequence, of CFS…Les Borysiewicz, a clinical virologist at Addenbrookes Hospital in Cambridge (now Chief Executive of the MRC, having succeeded Professor Colin Blakemore) (said) ‘Whatever causes CFS, it isn’t the virus itself’…Anthony Clare, psychiatrist and medical director of St Patrick’s Hospital in Dublin (now deceased), pointed out that…there have been many ‘fatigue’ diseases with shifting causes: ’Neurasthenia, food allergies, now viruses. Some people would always rather have a disease that might kill them than a syndrome they have to live with’ ” (Science 1990:249:4974:1240).

In their PNAS article that was published in April 1991, De Freitas et al noted that chronic fatigue immune dysfunction syndrome (CFIDS) “may be related or identical to myalgic encephalomyelitis” and examined adult and paediatric CFIDS patients for evidence of human retroviruses (HTLV types I and II). As the CFIDS Chronicle article noted, the Wistar team looked at the peripheral blood DNA to see if they could find messenger RNA (mRNA) encoding for a viral segment of the HTLV-II virus.

At that time, known human retroviruses were the human immunodeficiency viruses 1 and 2 (HIV-1 and HIV-2) which are known to cause AIDS, and human T-lymphotropic viruses HTLV-I which causes lymphoma and HTLV-II which causes leukaemia (Hunter-Hopkins ME-Letter, October 2009). The four segments of the HTLV-II virus are referred to as the env, gag, pol and tax.

After a two year study, De Freitas et al provided evidence for HTLV-II-like infection of blood cells from CFIDS patients (and also to a lesser extent from people closely associated with them). This evidence was further substantiated by patient reactivity to proteins with the molecular weights reported for HTLV-I and HTLV-II antigens.

In their article, De Freitas et al said: “The frequency of these antibodies in CFIDS patients compared with healthy non-contact controls suggests exposure / infection with an HTLV-like agent rare in healthy non-contact people”.

Following the Wistar findings, researchers at the US Centres for Disease Control (CDC) allegedly attempted to replicate De Freitas’ work but failed to do so; this was suggested to be because certain scientists appeared eager to discount any possibility of a retroviral association with CFIDS. De Freitas defended her work and insisted that the CDC investigators had modified her assays, with the result that her work could not be replicated by the CDC.

De Freitas was publicly discredited; her research funding was discontinued and her research abandoned; she was subjected to what appeared to be attempts to destroy her professional reputation. Commenting on the subsequent discovery of XMRV (see below), ME/CFS expert Dr Paul Cheney of The Cheney Clinic was unambiguous: “Her work was unfortunately assaulted by the CDC. Her proposal to fly to the CDC in Atlanta to physically run the assays side by side with the CDC scientists was dismissed by the CDC” (http://cheneyclinic.com/a-retrovirus-called-xmrv-is-linked-to-cfs/538  ).

Read full article here:

http://www.meactionuk.org.uk/The-role-of-viruses-in-ME.htm

http://tinyurl.com/ykjveep

http://www.meactionuk.org.uk/The-role-of-viruses-in-ME.pdf

http://tinyurl.com/y8m8s8h

Two responses around XMRV: Prof Simon Wessely; Dept of Health

Two responses around XMRV: Prof Simon Wessely; Dept of Health

Shortlink: http://wp.me/p5foE-2mS

Two users of the Whittemore Peterson Institute Facebook site have kindly given permission for the following responses to be reproduced here, on ME agenda.

Update: The response from Professor Simon Wessely following an enquiry by a member of the public has been removed since permission for publication and the terms under which Professor Wessely’s response might be republished had not been discussed.  A copy of the response was also published by me via Co-Cure together with the response from the Department of Health.  This is also being removed.

——————-

Whittemore Peterson Institute on Facebook

Heath reported on 12 November that he wrote to the Department of Health.  The DoH response was:

Thank you for your email of 28 October to the Department of Health about xenotropic murine leukemia virus-related virus and chronic fatigue syndrome/myalgic encephalopathy (CFS/ME).

The Department of Health agrees with the World Health Organization’s classification of CFS/ME as a neurological condition of unknown cause. The Department also agrees that CFS/ME is a genuine and disabling illness and can have a profound effect on those living with the condition. That is why research breakthroughs such as the one outlined in your email, are so important to developing the knowledge base.

The National Institute for Health and Clinical Excellence (NICE) clinical guidelines are updated as needed so that recommendations take into account important new evidence. However, as I hope you will appreciate, as NICE is an independent body, the time-frame for revising guidance and the evidence it uses are matters entirely for NICE. You may therefore wish to raise this issue directly with NICE’s Chief Executive, Andrew Dillon, at the following address:

NICE
MidCity Place
71 High Holborn
London WC1V 6NA

I think it also helpful to emphasise that NICE clinical guidelines are just that – guidelines for healthcare professionals use in conjunction with their clinical judgement and based on an individual assessment of each patient’s needs. The guideline recognises that there is no one form of treatment to suit every patient and it does not force patients into treatments they do not want.

The guideline emphasises a collaborative relationship between clinician and patient, that treatment and care should take into account personal needs and preferences, and that healthcare professionals should recognise that the person with CFS/ME is in charge of the aims of the treatment programme.

Cognitive Behavioural Therapy is a rehabilitative approach designed to modify the way patients think and behave about their illness and so improve physical symptoms. In common with other illnesses and conditions where it has been successfully used such as chronic pain, cancer, heart disease and diabetes, its use does not imply that the cause of the illness is psychological.

The Department feels that it is not helpful to differentiate between biomedical and psychosocial treatments as, based on clinical evidence that is currently available, patients are best served by a holistic approach.

You also comment on the paucity of bio-medical research. I know that many of the Department’s stakeholders see biomedical research as the key to developing new treatments and the Department appreciates the concern about a lack of biomedical research in this area.

As you may know, the main agency through which the Government supports medical and clinical research is the Medical Research Council (MRC). The MRC is wholly independent in its choice of which research to support and it does not generally earmark funds for particular topics. It maintains a rigorous decision making process and only funds research that is likely to make a significant contribution to knowledge and is a good use of taxpayers’ money. Decisions to support proposals are taken on the grounds of scientific quality and whether the research proposed would be likely to inform the knowledge base. There is certainly no bias, and the Department knows that the MRC remains committed to funding scientific research in all aspects of CFS/ME.

The Department understands that the MRC continues to attract a small number of proposals for biomedical research. The problem is that there appears to be a shortage of good and innovative ideas within the scientific community itself. This is something the Department knows that the CFS/ME community and the MRC are aware of, and the MRC have endeavoured to address this by engaging with patient groups to encourage high quality research proposals. The MRC continues to acknowledge the importance of research into CFS/ME, and it is difficult to see what more the MRC could do without lowering the quality threshold.

I hope this reply is helpful.

Yours sincerely,

Priya Bassan
Department of Health

Related information:

Source: ME Research UK

http://www.meresearch.org.uk/information/publications/casetoanswer.html

The Medical Research Council: a case to answer?

[...]

CFS/ME projects currently funded by the MRC
(Sources: MRC website; Hansard, written answers)

•Two large clinical trials of new approaches to treating CFS/ME:
          PACE (Pacing, Activity and Cognitive Behaviour Therapy: a Randomised Evaluation, £2,076,363) [Prof. PD White, Psychological Medicine, Queen Mary and Westfield College]
          FINE (Fatigue Intervention by Nurses Evaluation, £824,129) [Dr AJ Wearden, Psychological Science, Uni. of Manchester]

•A preliminary epidemiological project to test the feasibility of identifying the risk factors for persistent symptoms of fatigue and abdominal and widespread pain (£118,263) [Prof. F Creed, Psychological Medicine, University of Manchester]

•An epidemiological study to assess ethnic variations of the prevalence of a CFS-like illness, associations with potential risk factors, and coping behaviours (£162,145) [Prof. K Bhui, Cultural Psychiatry and Epidemiolgy, Queen Mary and Westfield College]

•Indirect support through a trial exploring the management of patients with persistent unexplained symptoms [Specifics unknown]

•One project was mentioned in Hansard (12th June 2008) but is not on the MRC website: General and specific risk markers and preventive factors for chronic fatigue and irritable bowel syndromes (£367,000) [Dr C Clark, Centre for Psychiatry, Barts and The London School of Medicine]

 

Table. Unfunded applications to the MRC between 2002 and 2008

Time-frame   (number of applications)   CFS/ME subject area

2002 to 2005 (11 total) Neurophysiology of fatigue; Population-based/epidemiological studies (4 applications); Neurotransmitters and stress; Neuroimaging; Clinical and laboratory characterisation physiology/diagnosis); Dietary intervention — RCT; Facilitated self-help — RCT; Psychosocial and genetic factors in young people

2005 to 2006 (12 total) Pathophysiology, including studies regarding genetics/biomarkers, immunology and neuroimaging (7 applications); Population-based/epidemiological studies (3); Primary care study; Experimental medicine study

2006 to April 2007 (7 total) Cognitive outcomes in children — pathophysiology; Epidemiological studies — epidemiology; Biomarkers; Pathophysiology (2 applications); Molecular pathogenesis — pathophysiology; Molecular and genetic characterisation — pathophysiology; Neuroimaging — pathophysiology

May 2007 to June 2008 (3 total) Biomarkers — pathophysiology; Management and treatment — intervention; Management and treatment — observational study

Text of Agenda for November MRC CFS/ME Workshop and AfME response

Text of Agenda for MRC CFS/ME Expert Group Research Workshop 19-20 November 2009 and Action for M.E.’s Facebook response

Shortlink: http://wp.me/p5foE-2mD

Below is the text of the Agenda for the November MRC Workshop.  I have posted links for this Agenda and other information provided by the MRC, yesterday, on the Facebook Walls of Action for M.E. and the ME Association.  At the time of writing, neither organisation has published a copy of the Agenda, itself, on its main website.

Since flagging up the Agenda on Action for M.E.’s Facebook site, and some ensuing comments by users of the site, the following has been added by the moderators:

http://www.facebook.com/actionforme

“Sir Peter has asked Professor Holgate to ensure during the course of the two-day event that particular consideration be given to the XMRV findings and current efforts to replicate them by other researchers.”

“Action for M.E. MRC CFS/ME research workshop Sir Peter Spencer, CEO, Action for M.E. and other M.E. charity representatives will attend a multi-disciplinary workshop for researchers, organised by the Medical Research Council (MRC), 19-20 November.”

“The meeting, chaired by Professor Stephen Holgate, MRC Professor of Immunopharmacology from Southampton University, aims to encourage new research into M.E./CFS, harnessing the latest technologies and scientific thinking to develop a proper understanding of the underlying disease mechanisms.

Papers circulated include information about XMRV, the retrovirus identified in 68 out of 101 CFS patients by researchers at the Whittemore Peterson Institute in Reno, USA. Although the sample is small, the results have led to calls for greater investigation into the biology of M.E.

Sir Peter has asked Professor Holgate to ensure during the course of the two-day event that particular consideration be given to these findings and current efforts to replicate them by other researchers.

Anyone who wishes to contact Sir Peter about the workshop may do so by e-mailing consultations@afme.org.uk

“Scientists participating in the MRC workshop are already due to hear short presentations on phenotyping and epidemiology, autonomic dysfunction, fatigue, sleep, pain, neuroimaging, new technologies, immune dysregulation, infection and virology.

There will be an opportunity for group discussion before delegates split up into workshops.

These will consider:
- capitalising on current issues and UK scientific strengths
- new technologies and technological platforms
- national resources eg. patient cohorts
- partnership models
- research prioritisation
- other issues.

Professor Holgate will then summarise the workshop’s discussions, which will indicate a way forward for future work.”

 

Text of Agenda for MRC CFS/ME Research Workshop 19-20 November 2009

Note: I am advised by Ms Parker, MRC Corporate Governance and Policy, that “We are still in discussion with colleagues regarding the participants list and will respond to this part of your request in due course.”  I will post the list of participants when the MRC has fulfilled this part of the FOI request for information.

Also note that the timings, as set out in the document for the afternoon session of Day One, are squiffy. I have reproduced as supplied by the MRC in the PDF.

AGENDA in PDF format here: http://wp.me/p5foE-2mj

——————————

[MRC Logo] Medical Research Council

MRC CFS/ME Research Workshop

To be held on Thursday 19th & Friday 20th November

Location: Hethrop Park Resort (Chipping Norton, Oxfordshire OX7 5UF)

Agenda – Thursday 19th November

13:00 Registration; Lunch
Tea & Coffee
____________________________________________

13:30 Welcome and Introduction by Professor Stephen Holgate

Aims of the Workshop
____________________________________________

Short Presentations:

Topic    Speaker

13:45 CFS/ME phenotyping & epidemiology    Dr Esther Crawley

14:00 Autonomic dysfunction Professor    Julia Newton

14:45 Fatigue    tbc

14:15 Sleep Professor    Jim Horne

14:30 Pain Professor    Maria Fitzgerald

____________________________________________

15:00 Tea & Coffee
____________________________________________

15:30 Neuropsychology    Professor Gijs Bleijenberg

15:45 Neuroimaging    Professor Phil Cowen*

[*Ed: Philip Cowen is Professor of Psychopharmacology and MRC Clinical Scientist at the University of Oxford. His research and clinical interests are in the biochemistry and treatment of mood disorders, and particularly the pharmacological management of resistant depression.]

16:00 New Technologies    Professor Chris Ponting

16:15 Immune dysregulation/Infection    Professor Tony Pinching

16:00 Virology    Professor Paul Moss

____________________________________________

16:45 Tea & Coffee
____________________________________________

17:00-18:00 Group discussion
____________________________________________

19:00 Dinner
____________________________________________

Agenda – Friday 20th November

09:00 Introduction – brief for morning session – Professor Stephen Holgate

09:15 Working group discussions

‘What would you like to see the field respond to?’

Areas for consideration:
. capitalising on current issues and UK scientific strengths
. new technologies and technological platforms
. national resources e.g. patient cohorts
. partnership models
. other issues

______________________________________

10:45 Tea & Coffee
____________________________________________

11:00 Whole group discussion

11:45 Summing up and next steps – Professor Stephen Holgate

12:00 Close
____________________________________________

AGENDA in PDF format here: http://wp.me/p5foE-2mj

Link Back

Agenda: MRC CFS/ME Research Workshop 19-20 November 2009 and additional information provided by the MRC under FOIA:

WordPress Shortlink: http://wp.me/p5foE-2mj

The Agenda and Minutes of the meeting on 15 December can be downloaded here or opened in PDF format here:

PDF: Minutes CFS/ME Expert Group Meeting 15 December 2008

The list of members can be opened in PDF format here:

PDF: CFS/ME Expert group membership

Term of Reference can be opened in PDF format here:

PDF: Finalised Terms of Reference for CFS/ME expert group

or go to MRC site for full article and files:

Chronic Fatigue Syndrome/Myalgic Encephalomyelitis 

( http://www.mrc.ac.uk/Ourresearch/ResearchFocus/CFSME/index.htm )

Top scientists to meet at Cleveland Clinic on trail of XMRV

75 top scientists are flying in to convene on Wednesday at the Cleveland Clinic.

Top scientists to meet at Cleveland Clinic on trail of XMRV, a suspect in prostate cancer

WordPress Shortlink: http://wp.me/p5foE-2m6

http://www.cleveland.com/healthfit/index.ssf/2009/11/top_scientists_to_meet_at_clev.html

By Angela Townsend, The Plain Dealer
November 10, 2009, 6:00AM

Dr. Robert Silverman is a cancer biologist at the Cleveland Clinic instrumental in the discovery of the XMRV virus. Medical reporter Angela Townsend discusses this story at 7:35 this morning with WCPN FM/90.3’s Eric Wellman on Tuesday Check-up. Listen in or log in online. The virus XMRV has become a favorite topic in the scientific community — three years after its initial discovery in prostate cancer tumors by researchers from the Cleveland Clinic and the University of California, San Francisco…

[...]

Capitalizing on the excitement and heightened spirit of collaboration, 75 of the top scientists nationwide studying XMRV are flying in to convene Wednesday at the Clinic.

“This is the first meeting of the major players in the area of XMRV,” said John Coffin of the department of microbiology at Tufts University in Boston. “I think there’s going to be a lot of excitement and a lot of new information presented.”

Contact Angela Townsend: atownsen@plaind.com  or 216-999-3894.

Read full article here

 

Link back

For initial Whittemore Peterson Press Release and NIH (National Institutes of Health) News Release go here: http://wp.me/p5foE-272

For Science paper go here: http://wp.me/p5foE-2is

Go here for all previous XMRV Round ups and postings in reverse date order: http://meagenda.wordpress.com/category/xmrv/

XMRV Retrovirus presentations: Klimas, de Meirleir, Hyde

XMRV Retrovirus presentations: Klimas, de Meirleir, Hyde

WordPress Shortlink: http://wp.me/p5foE-2lh

Dr Nancy Klimas lecture, Florida, 7 November 2009

A video of Dr Nancy Klimas’s 7 November lecture is expected soon on Dan Moricoli’s CFS-ME Network, here:

http://cfsknowledgecenter.ning.com/

An earlier video, “Dr Nancy Klimas discusses the XMRV virus discovery, what it means, what’s next and what you can do”, recorded 12 October, can be viewed in the Video Section here:

http://cfsknowledgecenter.ning.com/video/klimas-on-xmrv

————–

Göteborg Conference, Sweden

Dr Byron Hyde: Missed Diagnoses
Dr Kenny de Meirleir: End of an Era of Medical Negation

Göteborg 10th November: Professional’s Day
Göteborg 11th November: Public meeting http://www.rme.nu/node/85

Malmö 12th November: Public Meeting http://www.skane.se/templates/Page.aspx?id=266536

According to Whittemore-Peterson Institute on Facebook, the Byron Hyde and Kenny de Meirleir lectures in Göteborg on Professionals Day, 10 November will be videotaped and placed on the internet.  A DVD will also be available for purchase at Riksföreningen ME Göteborg (email: goteborg@rme.nu).

http://www.rme.nu/lokala-foreningar/rme-goteborg

A PDF of Dr Hyde’s conference address is available here:

http://www.nightingale.ca/documents/GoteborgConference.pdf 

(Pages 7 and 8 for section: “The Whittemore Peterson Institute CFS – Retrovirus Announcement” )

Göteborg and Malmo, Sweden
M.E. Conferences: November 2009

Link back

For initial Whittemore Peterson Press Release and NIH (National Institutes of Health) News Release go here: http://wp.me/p5foE-272

For Science paper go here: http://wp.me/p5foE-2is

Go here for all previous XMRV Round ups and postings in reverse date order: http://meagenda.wordpress.com/category/xmrv/

Correspondence between Stephen Ralph and Dr Charles Shepherd

Correspondence between Stephen Ralph and Dr Charles Shepherd

WordPress Shortlink: http://wp.me/p5foE-2jm

The opinion piece below, which includes extracts from recent correspondence with Dr Charles Shepherd is authored and published by Stephen Ralph; the views and opinions expressed are the views and opinions of Mr Ralph and any comments or queries resulting out of this opinion piece should be addressed to Mr Ralph and not to ME agenda.

Stephen Ralph maintains a website at  www.meactionuk.org.uk 

Dr Charles Shepherd is an Honorary Medical Advisor and a Trustee/Director of the ME Association http://www.meassociation.org.uk/

A copy of the statement which Stephen Ralph quotes from is here:

 XMRV and ME/CFS: WHAT DO WE KNOW SO FAR? AND WHAT DON’T WE KNOW? (VERSION 3) (04.11.09)  http://wp.me/p5foE-2kq

—————–

By Stephen Ralph  ME Action UK

Permission to Repost

06 November 2009

Like many of you, I was alarmed when I read the recent MEA XMRV Statement No.3 particularly because of one telling sentence.

I decided to ask Dr Shepherd a series of questions and although I had several answers, I had no answer at all to one important question that I asked several times.

I asked Dr Shepherd about this statement.

“Demonstrating a link between a retrovirus and ME/CFS does not, by itself, resolve the physical vs psychological debate.

Research studies have demonstrated links between retroviruses and diseases as diverse as autoimmune disorders (which could be relevant to ME/CFS), immunodeficiency diseases, multiple sclerosis, tumours, anaemias and even schizophrenia.”

In reply I got the following from Dr Shepherd.

“I don’t think this comment will have any effect whatsoever on psychiatry.

Psychiatrists already know that viruses and psychiatric illness can sometimes be linked.

I put this info into version 3 because some people are wrongly assuming that having a viral link in an illness means that it must be physical rather than psychological. And that the physical vs psychological battle in ME/CFS is now almost over. I only wish…..

Retroviruses may be involved in schizophrenia and it is being said the up to 40% of people with autism have XMRV.”

I then asked Dr Shepherd what he would do if he found he was XMRV negative and how this might impact on his judgment.

In reply I had the following from Dr Shepherd…

“I don’t know my XMRV status. I obviously could have access to XMRV testing facilities. But as knowing my XMRV result isn’t going to affect either my diagnosis of ME or the management of my illness at this stage I don’t see any point in being tested.”

Lastly, I asked Dr Shepherd if he did or did not support the views of Professors Simon Wessely, Michael Sharpe and Peter White.

I asked this question twice for the sake of clarification.

Dr Shepherd has decided not to answer that question.

I asked the question because on numerous occasions the MEA have released hedge betting, sitting-on-the-fence statements or cheek turning Statements that effectively support the agenda of Somatoform Psychiatry or completely ignore the agenda of Somatoform Psychiatry.

The statement regarding XMRV not ending the debate on mental v physical is for my eyes indicating that yet again the MEA and Dr Shepherd are entertaining the possibility that Wessely White and Sharpe are right.

Dr Shepherd – you should be actively ending the involvement of Professors Wessely, White and Sharpe and you should be representing the total “State of Science” from across the Atlantic as is the case with the ESME – see their website for example…

http://esme-eu.com/news/category7.html

…instead of selectively picking what you want to feed your members and back peddling on the profound implications of XMRV and what was said at the CFSAC last week.

As we all know, the liaison faction of psychiatry firmly and militantly assert that CFS is a functional psychosomatic syndrome and that ME does not exist at all.

We know that the likes of Wessely, White and Sharpe are trying to get CFS into the next edition of the DSM – DSM-V and reclassified in ICD-11.

Both Action for ME and the ME Association are doing nothing to stop this agenda.

I asked Dr Shepherd some time ago if he or the MEA were going to do anything about the CSSID DSM-V ICD-11 agenda and Dr Shepherd said he was too busy and it wasn’t on his list of things to do.

In my view, the ME Association is not a lot more than the Public Relations arm of Action for ME.

Yes they seem approachable and yes they seem to press all the buttons that please some of their members.

But as soon as you ask anything considered “controversial” or important – then Dr Shepherd and/or the MEA goes silent and refuses to answer the question as is the case by default with Action for ME.

It seems to me that here in the UK and for many years, the ME population are being held hostage by the mental health movement who seem to have castrated both Action for ME and the ME Association who between them dominate the arena yet lay silent and do nothing to counter the mental health agenda…

So it seems to me that neither charity actually give a damn about the concerns of the ME community unless those views accord with their agenda that they will not discuss when challenged in ANY detail.

They say the devil is in the detail but we do not know what the detail is because when we ask we get nothing back.

Under these circumstances we need those over in the USA and those in the UK with Independence of mind and purposes such as ME Research UK, the 25% ME Group and Invest in ME – to come to the rescue of the UK ME patient population.

If people are not happy with this e-mail I have written and you think I am being unfair then you should ask Dr Shepherd and the MEA yourselves and get the answers he would not give to me or the many others who have asked similar questions over the years that never get answered.

Why does the MEA turn the other cheek and choose not to robustly challenge the views of Professor Wessely and his colleagues and instead state that “they already know” so that these individuals are therefore beyond challenging…

How exactly does liaison psychiatry “already know” that retro-viruses cause mental illness and does the MEA believe that XMRV potentially causes functional mental illness in people with ME? If not then why stay silent – creating a space for the opposition to occupy.

Why does the MEA put out neutered statements that reflect the views of liaison psychiatry instead of using all the evidence available to robustly and technically challenge those views?

Why is the ME Association calling for the use of the CDC Fukuda Criteria in UK XMRV research when the Fukuda criteria has been and is still being exploited by Wessely et al due to its well known ability to produce a heterogeneous patient group and therefore research results that are by default inconclusive and “mixed” and challengeable by those with a mental health agenda?

Why does the ME Association not firmly call for the use the Canadian criteria or use both Fukuda and the Canadian criteria in parallel research to make the research outcomes more meaningful and less open to exploitative deconstruction when the ME Association at one time adopted the Canadian Criteria by a democratic vote and then quietly swept that democratic vote under their carpet?

This is all about accountability. We should be given full answers to all of the above questions.

What is wrong in asking?  Why does that make us bad?

Yours sincerely,

Stephen Ralph

www.meactionuk.org.uk

XMRV Retrovirus Round up 22: WPI Press Release, ESME, 74 CFSAC meeting videos

XMRV Retrovirus   Whittemore Peterson   Institute Science   Mikovits   Peterson   Chronic Fatigue Syndrome

XMRV Retrovirus: Round up 22: WPI Press Release, ESME, 74 CFSAC meeting videos

WordPress Shortlink: http://wp.me/p5foE-2jN

Press Releases

PDF here: WPI Release Diagnostic Test

http://www.wpinstitute.org/WPI%20Release%20Diagnostic%20Test.pdf

FOR IMMEDIATE RELEASE

Frankie Vigil
R&R Partners
775-336-4555
frankie.vigil@rrpartners.com

Viral Immune Pathology Diagnostics Introduces New Test for XMRV Patients and Clinicians
-Net proceeds from test dedicated to further WPI research-

RENO, Nev. – The Whittemore Peterson Institute (WPI) has recently published a research study revealing the prevalence of XMRV in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome, ME/CFS or what has most recently been called, X associated neuro-immune disease, (XAND). In response to an overwhelming request for a diagnostic test for XMRV, WPI has temporarily agreed to allow Viral Immune Pathology Diagnostics (VIP Dx) to begin offering the identical tests that have been extensively validated using the same technology developed by Drs. Lombardi and Mikovits and their colleagues as reported in Science.

VIP Dx is a small state certified laboratory in Reno, Nevada that was formed in response to the September 11, 2001 crisis which resulted in the cessation of blood sample shipments between the United States and Europe. Faced with the loss of important lab tests impacting patients with neuro-immune diseases, the Whittemore family made the decision to support the lab in Reno.

“Our family made it possible for the lab to not only continue delivering diagnostic tests to doctors, but also help the WPI bring cutting edge biomarkers of disease to this field of medicine, such as the tests for XMRV,” said Annette  Whittemore, Founder and President of WPI. “Tests conducted for XMRV, and other tests that support the diagnostic process in this field, will support the continuation of vital work at WPI through our donation of all of our net proceeds.”

XMRV test acceptance commenced at VIP Dx this month.

For more information about the XMRV test kit, visit www.vipdx.com

Whittemore Peterson Institute  http://www.wpinstitute.org/

The Whittemore Peterson Institute for Neuro-Immune Disease exists to bring discovery, knowledge, and effective treatments to patients with illnesses caused by acquired dysregulation of the immune system and the nervous system, often resulting in lifelong disease and disability. The WPI is the first institute in the world dedicated to neuro immune diseases, integrating patient treatment, basic and clinical research and medical education.

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CFSAC Two Day meeting: NIH videocasts now available plus 74 Video segments

http://cfsknowledgecenter.ning.com/video

74 videos covering the CFSAC Two Day meeting (29 – 30 October) on Dan Moricoli’s Ning ME-CFS Community.

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NIH will be counting viewing figures to assess interest in making videocasts for these meetings available worldwide – so please view the videocasts on the NIH site:

Videocasts of CFSAC meeting 29-30 October 2008

Around 12 hours of video of the two day CFSAC meeting is now available at:

http://videocast.nih.gov/PastEvents.asp

Chronic Fatigue Syndrome Advisory Committee Meeting (CFSAC) – Day 1
Thursday, October 29, 2009
HHS Office on Women’s Health (OWH)
Total Running Time: 06:43:49

http://videocast.nih.gov/PastEvents.asp

Chronic Fatigue Syndrome Advisory Committee Meeting (CFSAC) – Day 2
Friday, October 30, 2009
HHS Office on Women’s Health (OWH)
Total Running Time: 05:15:09

Presentation

Dr David Bell’s PowerPoint slides: http://www.hhs.gov/advcomcfs/meetings/agendas/bell_factitious_102909.ppt

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Media

The Street   |  3 November 2009

http://www.thestreet.com/_yahoo/story/10620979/1/hemispherx-cops-to-ampligen-fda-delay.html

Ref: Hemispherx press release:

http://finance.yahoo.com/news/Hemispherx-Biopharma-Updates-pz-1535703186.html 

See also:

http://philadelphia.bizjournals.com/philadelphia/stories/2009/11/02/daily2.html

Hemispherx cops to Ampligen FDA delay

PHILADELPHIA, Pa. (TheStreet) – Hemispherx Biopharma(HEB Quote) issued an “update” to the regulatory status of its chronic fatigue syndrome drug Ampligen in which the company essentially admits that its prior public statements were false and misleading.

Monday’s statement was likely crafted by Hemispherx’s lawyers as a way to help CEO Bill Carter wiggle out of public statements he made in May and June claiming the Ampligen application to the U.S. Food and Drug Administration to be complete. Carter insisted regulators weren’t asking for any additional information on Ampligen.

Read full article here

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Patient organisation statements

ESME www.esme-eu.com

Dear Whittemore Peterson Institute,

The Scientific Panel, the Board of Directors and the staff of ESME wish to congratulate the Whittemore Peterson Institute on the groundbreaking work they are performing in the area of neuro-immune diseases and especially their work with the XMRV virus. We applaud the thoroughness of your research and the openness with which you are sharing this research information with the world. We believe that by sharing scientific knowledge with this openness, you are starting a new era of scientific cooperation.

ESME would like to help the Whittemore Peterson Institute with information flow in Europe. We have the capacity to professionally translate information to Danish, Dutch, German, Norwegian, French and Spanish and we have a professional website where information can be posted in any of these languages: www.esme-eu.com  

ESME has also established a database of approximately 3000 e-mail addresses of European scientists, doctors, medical associations, national and regional ME associations, politicians, journalists and other people interested in ME/CFS. This database allows us to easily distribute information to professionals in many fields. We will gladly use our resources to assist the Whittemore Peterson Institute with the distribution of information in Europe.

In 2009, ESME held two conferences in Norway to educate healthcare personal (and patients) about the diagnostics, treatment, causes and consequences of ME/CFS. ESME will continue organizing these conferences in the coming years throughout Europe. We would like to invite a representative of the WPI to be a guest speaker at future European conferences to help us inform and train European MD’s and therapists better.

With Kind Regards,

ESME

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Commentary

Cort Johnson’s Phoenix Rising website: http://aboutmecfs.org/Rsrcs/XMRVResources.aspx

Cort Johnson’s Blog and comments: http://aboutmecfs.org/blog/

Cort Johnson’s Forums: http://forums.aboutmecfs.org/

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About.com  Fibromyalgia  and CFS Blog  | 5 November 2009

XMRV & Updated Mechanism Theory of Chronic Fatigue Syndrome

The XMRV Discovery Series

Dr. Daniel Peterson, one of the researchers involved in the possibly groundbreaking XMRV findings, testified before the NIH’s Chronic Fatigue Syndrome Advisory Committee Oct. 29. Among the many things he presented was an updated theory of how chronic fatigue syndrome (CFS or ME/CFS) develops. (Thanks to Dr. David S. Bell and his newsletter, Lyndonville News for putting this into language that was easier to understand!)

Read full article here

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For initial Whittemore Peterson Press Release, NIH (National Institutes of Health) News Release, go here: http://wp.me/p5foE-272

For Science paper go here: http://wp.me/p5foE-2is

Click here for all previous XMRV Round ups and postings in reverse date order: http://meagenda.wordpress.com/category/xmrv/

The Definition Petition

Petition webpage: http://CFSdefinitionpetition.notlong.com
i.e. http://www.ipetitions.com/petition/empirical_defn_and_CFS_research

If you haven’t already signed it – sign the CFS Definition Petition today at: http://CFSdefinitionpetition.notlong.com

ME Association: Updates: Blood Donation, XMRV and ME/CFS Version 3

Two further statements around the XMRV study have been issued by the ME Association (UK) and are published, in full, below this preamble:

“There is an immediate need for international agreement and co-operation on the research criteria being used to select well-characterised ME/CFS patients for further research into XMRV. Otherwise, we could end up in 2010 with a collection of conflicting results on prevalence because different international research groups have been using different patient selection criteria.

In the present situation, with many research groups reluctant or unwilling to use Canadian criteria, and not having stored samples from patients that meet Canadian criteria, the best way forward may be for everyone to agree to use Fukuda defined CFS. We may then be able to draw some conclusions about which people who come under the wide clinical spectrum of CFS clinical presentation have XMRV and which do not.”

Why is the MEA not recommending use of the more rigorous Canadian Criteria for replication studies?

Several years ago, the MEA held a formal postal ballot amongst its membership to vote for or against a proposal that the MEA should adopt the Canadian Criteria. Cases for and against adoption were published in the MEA’s magazine, ME Essential, with Dr Shepherd presenting the case against adoption. Of the very small percentage of the membership that returned a vote, the majority vote was in favour of adoption. The MEA announced the adoption “in principle” of the Canadian Criteria, then deftly kicked the Canadian Criteria under the carpet.

 “…Demonstrating a link between a retrovirus and ME/CFS does not, by itself, resolve the physical vs psychological debate. Research studies have demonstrated links between retroviruses and diseases as diverse as autoimmune disorders (which could be relevant to ME/CFS), immunodeficiency diseases, multiple sclerosis, tumours, anaemias and even schizophrenia.”

I am not a member of the MEA; I was barred from membership of the Association in 2005 by Chair’s Action. A subsequent application to become a member of the Association was voted against by the Board of Trustees. The Association has the power, within the framework of its constitution, its Memorandum and Articles of Association, to deny membership to anyone it decides not to admit to membership [Clause 4.1 (b)]. Were I a member, however, I would be demanding an explanation from Dr Shepherd of what he means by the first sentence of the statement above.

 

WordPress Shortlink: http://wp.me/p5foE-2jm

1] XMRV and blood donation – update following letter to the Chief Medical Officer (02.11.09)

2] XMRV and ME/CFS:  WHAT DO WE KNOW SO FAR?  AND WHAT DON’T WE KNOW? (VERSION 3) (04.11.09)

 

1] XMRV and blood donation – update following letter to the Chief Medical Officer (04.11.09)

http://www.meassociation.org.uk/content/view/1067/161/

XMRV and blood donation – update following letter to the Chief Medical Officer

The ME Association wrote to Sir Liam Donaldson, Chief Medical Officer at the Department of Health, on Tuesday 27 October about XMRV research. In particular, we raised the situation regarding people with ME/CFS and blood donation.

Click  http://www.meassociation.org.uk/content/view/1059 

to read a copy of this letter.  An acknowledgement from the CMO has been received.

We are today writing to the CMO again to pass on the interim guidelines about blood donation and ME/CFS in America that have been issued by Dr John Niederhuber from the National Cancer Institute, US National Institutes of Health. This information was requested from the NCI by the CFIDS Association of America and has been published on their website:

http://www.cfids.org/temp/xmrv-guidelines-nci.asp

The MEA is very keen to build up an international database on the situation regarding blood donation and any information from people or support groups in other countries would be welcomed.

Following contact and discussions last week with a number of virologists and retrovirologists involved with XMRV research, the MEA will be updating our position statement on XMRV later in the week.

We shall also be repeating our offer to help fund good quality XMRV research here in the UK through the MEA Ramsay Research Fund:

http://www.meassociation.org.uk/content/view/30/205/

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2] XMRV and ME/CFS:  WHAT DO WE KNOW SO FAR?  AND WHAT DON’T WE KNOW? (VERSION 3) (04.11.09)

http://www.meassociation.org.uk

Version 3 clarifies some of the points and queries raised in the previous two MEA statements and summarises the  various actions now being taken by the  ME Association.

It also updates the situation on XMRV research initiatives in the UK, testing for XMRV and refers to our letter to Sir Liam Donaldson, the Chief Medical Officer, regarding blood supplies and blood donation.

This summary is intended to be a balanced account which not only raises questions but is also very cautious when it comes to drawing any firm conclusions about the role of XMRV in ME/CFS at this very early stage in the research.

BACKGROUND

On Friday 9 October, the front page of the UK Independent newspaper carried a major news item under the heading ‘Has science found the cause of ME?’

This referred to new research findings from America which indicate that a recently discovered retrovirus, known as XMRV (xenotropic murine leukaemia virus-related virus), could be playing an important role in causing or maintaining ME/CFS. The news item was accompanied by a very supportive editorial about the need for recognition and research into ME/CFS. These two items can be read here:

http://www.meassociation.org.uk/content/view/1068/161/

The Independent story was soon followed up by the rest of the UK media, including the BBC. Most of the news reports gave a reasonably balanced and accurate account of the research. However, some reports incorrectly inferred that the cause of ME/CFS had now been conclusively discovered and that an effective antiviral treatment would soon be available. A selection of UK media reports can be found in the October news archive on the MEA website.

The actual research paper was published in the online edition of Science, along with a perspective written by John Coffin (Department of Molecular Microbiology, Tufts University, Boston, USA) and Jonathan Stoye (National Institute for Medical Research, London).

References:

Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome. Lombardi V et al. Science October 8 2009

http://www.sciencemag.org/cgi/content/abstract/1179052

Abstract

A new virus for old diseases? Coffin JM and Stoye JP.  Science October 8 2009 326; p215

http://www.sciencemag.org/cgi/content/abstract/1181349

These papers are also available on the WPI website http://www.wpinstitute.org

Additional online data from the study can be obtained if required.

XMRV AND PROSTATE CANCER

XMRV has also been found in an American study in men who have prostate cancer. This was partly why the ME/CFS study was carried out. However, the most recent study on XMRV in prostate cancer from Germany has queried any such a link and suggested that one possible reason could be a geographically restricted incidence of XMRV infections. An additional explanation involves the type of laboratory testing for XMRV used in the two studies. The precise role of XMRV in prostate cancer remains uncertain.

Reference:

Lack of evidence for xenotropic murine leukaemia virus-related virus (XMRV) in German prostate cancer patients. Retrovirology 2009, 6:92. Available on-line here:

http://www.retrovirology.com/content/6/1/92

MEA POSITION ON XMRV

These are potentially important research findings that could help with both the diagnosis and management of ME/CFS. We congratulate all those involved in deciding to do this research study.

However, a number of difficult questions have to be answered before anyone can conclude that this virus plays a significant role in either the cause, transmission, clinical assessment or management of ME/CFS.

The research has demonstrated a correlation between ME/CFS and XMRV – not that it is the causative infection.

Much more epidemiology and laboratory work now needs to be done to answer the essential points set out below:

o Carrying out further and larger studies using different populations of people in different countries with ME/CFS. This work should include people at different stages of the illness (to see if the virus is present in the same percentages in both early and late cases) and in all degrees of severity. Research in different countries is vital in view of the conflicting geographical findings relating to XMRV in prostate cancer.

o Using different international laboratories to test for evidence of the virus.

o Establishing a battery of properly validated tests for XMRV that can be consistently used in further research studies.

o Assessing what, if any, correlation there is between the presence of this virus and (a) severity of symptoms, (b) a clear infectious onset with a known infection, (c) immune system abnormalities, CD4 abnormalities in particular, and (d) various other factors involved in sub-grouping of people under the ME/CFS umbrella.

o Assessing to what extent this particular retrovirus virus is also present in other chronic conditions, especially those such as autism, multiple sclerosis and lymphoma where viral infections have been implicated as a causative factor.

o Assessing whether this virus is acting as a benign marker of disease or immune dysfunction, is a ‘passenger virus’, or whether it has a role in the actual disease process and development of symptoms.

o Investigating whether the presence of the virus in healthy people acts as a predisposing factor in the development of ME/CFS (possibly when another infective trigger appears) and/or prostate cancer – rather than being involved in the actual disease process.

o Investigating what effect, if any, the virus has in healthy people who carry it over a period of time.

o Assessing whether people with evidence of XMRV should be treated with antiretroviral medication, and if so developing a suitable antiviral drug or combination of antiviral drugs.

o Assessing whether animal model studies would help to increase our understanding of the way in which this virus may infect cells and possibly cause human disease.

TESTING FOR XMRV IN THE UK AND USA

Until these research findings have been properly replicated, and we have the answers to some of the above questions, there is no point in asking your doctor to be tested for XMRV. This is because the NHS does not currently have the facilities to do so and the testing procedures are only being used in a research capacity at present. But, if it does turn out that there is a consistent and strong association with ME/CFS, then testing for XMRV would almost certainly have to be made available on the NHS.

We are not aware of any private pathology laboratories here in the UK that are able to test for XMRV, or are intending to start offering to carry out testing.

Dr Vincent Lombardi, primary investigator and lead author of the Science paper is Director of Operations for XMRV testing at Viral Immune Pathology Diagnostics VIPDx – a commercial laboratory in America. This testing facility is not available to people living outside the US.

VIRAL TRANSMISSION

We know that some people with ME/CFS are now very concerned about the possibility of transmission of XMRV through what are termed body fluids (ie blood, saliva, semen). However, until we know more about what this virus does in the body it would be premature to start arriving at firm conclusions and recommending all kinds of restrictions to normal daily living.

Remember: we still do not know for certain whether this is a disease-causing virus in humans and whether it plays a role in causing or maintaining ME/CFS.

And if this virus was behaving as an ‘ME virus’ in the way that HIV, another retrovirus, causes and transmits HIV infection, often leading to AIDS, there would be a significant number of sexual partners of people with ME/CFS developing ME/CFS. But this is clearly not the case.

One simple way of obtaining some early clues about viral transmission of XMRV would be to test for the presence of the virus in healthy partners and offspring of people who have the infection and comparing the findings to a control group of people that have no such link.

PRESENCE OF XMRV IN THE HEALTHY POPULATION

If this virus is also present in up to 4% of the normal healthy population here in the UK (ie around 2.4 million, or ten times the number of people who have ME/CFS), as appears to be the case in America, and it does play a significant role in diseases such as ME/CFS and prostate cancer, there will be widespread and very serious implications for public health, blood donation etc. This could also include vaccination against the virus and treating people who are XMRV positive. These are complex decisions which can only be made in the light of further research studies.

BLOOD DONATION AND XMRV

In relation to blood donation in the UK, current advice is that people with ME/CFS who have symptoms, or are receiving treatment, should not donate blood. It would seem sensible in the short term, until we know more about transmission and pathogenicity of XMRV, to consider extending this restriction to people who have recovered from ME/CFS. It seems strange that many overseas countries have not followed the UK lead on blood donation and ME/CFS.

The MEA has now written to Sir Liam Donaldson, Chief Medical Officer at the Department of Health, regarding the possibility of XMRV being transmitted via human blood products and the implications that this has for blood donation. A copy of this letter can be read here:

http://www.meassociation.org.uk/content/view/1059/

The CFIDS

Association of America has been issued with guidance from the National Cancer Institute regarding blood donation in the US. The guidance can be read on the CFIDS website:

http://www.cfids.org/temp/xmrv-guidelines-nci.asp

WHAT CAN WE LEARN ABOUT THE ROLE OF INFECTION FROM OUTBREAKS OF ME/CFS?

It should be noted that unlike the retroviral infection HIV, ME/CFS is an illness that occurs both sporadically and in highly localised acute geographical outbreaks, often involving closed communities such as schools and hospitals, where there is no obvious evidence of bodily fluid transmission. This fact would obviously question the role of XMRV as a precipitating infection in the onset of the illness.

In the pivotal Royal Free Hospital outbreak of ME back in 1955, far more than 4% of a previously healthy population of doctors and nurses contracted an unknown infection at roughly the same time (the hospital had to close due to lack of staff). This fact would question the role of XMRV as a key predisposing factor if it only occurs in 4% of the population.

TREATMENT OF XMRV: ANTIRETROVIRAL DRUGS AND VACCINE

Until we know more about the possible role of XMRV in ME/CFS there is no point in asking your doctor about antiviral drug treatment. If it turns out that the virus does play a role in causing or maintaining ME/CFS then antiviral drug treatment will need to be investigated. This will involve clinical trials to test possible drug treatments for both safety and efficacy – a process that normally takes a considerable amount of time and money.

The 2007 NICE Guideline on ME/CFS specifically states that doctors should not use antiviral medication to treat ME/CFS. This dogmatic position is unlikely to change without clear evidence of benefit in good quality randomised clinical trials. We understand that the NICE guideline will be reviewed in late 2010.

Vaccination against XMRV has also been raised as a possibility.

ROLE OF THE MEA RAMSAY RESEARCH FUND, VOLUNTEERING FOR RESEARCH and THE MEDICAL RESEARCH COUNCIL

The ME Association is keen to progress this research here in the UK through any way we can help. We have already made contact with virologists and retrovirologists who are interested in this virus here in the UK, and we are aware of at least four sound research groups who are keen to pursue this work. Funding from the Ramsay Research Fund (RRF) could be made available very quickly if we receive a good quality research proposal. However, our contacts and discussions with UK researchers so far indicate that short term funding is not an immediate problem and that initial plans can probably be covered from existing budgets.

More information on the work of the RRF can be found here:

http://www.meassociation.org.uk/content/view/30/205/

Since publication of these results it has become apparent that a number of international research groups outside the US and UK are also intending to try and confirm or refute the findings. The MEA has been contacted in relation to two such groups from overseas. This is obviously good news and should help to clear up some of the immediate uncertainties.

If volunteers are required for any research taking place in the UK we will place an announcement on the MEA website.

The Medical Research Council’s Expert Group on ME/CFS research (membership includes Dr Jonathan Kerr and Dr Charles Shepherd) will be holding a two day research workshop on 19 – 20 November where XMRV will obviously be one of the topics under discussion.

SELECTING PEOPLE FOR FURTHER RESEARCH STUDIES

There is an immediate need for international agreement and co-operation on the research criteria being used to select well-characterised ME/CFS patients for further research into XMRV. Otherwise, we could end up in 2010 with a collection of conflicting results on prevalence because different international research groups have been using different patient selection criteria.

In the present situation, with many research groups reluctant or unwilling to use Canadian criteria, and not having stored samples from patients that meet Canadian criteria, the best way forward may be for everyone to agree to use Fukuda defined CFS. We may then be able to draw some conclusions about which people who come under the wide clinical spectrum of CFS clinical presentation have XMRV and which do not.

Besides using stored blood samples, research needs to involve fresh clinical cases, as well as other disease groups (particularly inflammatory conditions with immune activation) and properly matched healthy controls.

KEY FACTS ABOUT THE XMRV RESEARCH

http://www.wpinstitute.org

o An American group from the Whittemore Peterson Institute, in collaboration with the National Cancer Institute and the Cleveland Clinic, have reported finding evidence of a human retrovirus known as XMRV in blood samples taken from people with ME/CFS.

o Using peripheral blood mononuclear cells, DNA (viral genetic material) from the virus was found in 67% of patients (68/101) compared to 3.7% in healthy controls (8/218).

o The XMRV virus was shown to grow in cell culture in the laboratory.

o Further studies have found that 95% of people with ME/CFS have antibodies to the virus – indicating an immune response to a recent or past infection.

o Blood samples were collected from people with what is referred to in the paper as CFS who live in different parts of the United States, as well as from healthy controls. More information on the patient and control cohorts can be found on the WPI website.

o A more detailed, but easy to understand, summary of the XMRV research has been prepared by Dr Suzanne Vernon for the CFIDS Association of America. This can be read at the CFIDS website. A press release summary produced by the National Cancer Institute is also worth reading:

http://www.cfids.org/cfidslink/2009/110402.asp

o The paper in Science does not provide any detailed information about the patient group (ie age, gender, illness characteristics) or control group. However, a report on the research published in The Wall Street Journal states that 20/101 people in the CFS group also had a lymphoma, a type of cancer affecting the lymph nodes. Questions have therefore been raised about the inclusion of these patients in the CFS group, as well as the makeup of the control group and how these patients were selected. See commentary from Professor Andrew Lloyd published on the website of the ME/CFS Society of NSW, Australia:

http://www.me-cfs.org.au/node/448

The WPI have now stated in a website response that none of the results in the Science paper relate to people with CFS plus lymphoma.

KEY FACTS ABOUT RETROVIRUSES

o Retroviruses infect a wide range of animal species.

o Human retroviruses consist of HIV (causing AIDS) , HTLV-1 (causing T-cell leukaemias and lymphomas) and HTLV-2 (often asymptomatic and not yet clearly linked to any specific disease).

o They were discovered in the 1980s when it became possible to culture T-cells in vitro.

o They infect CD4-bearing lymphocytes – a special type of immune system cell that is derived from the thymus gland.

o Endogenous retroviruses (ERVs) are also found in humans and usually cause no ill effects. Defective retroviruses which integrate into the host genome are passed down from generation to generation. And 2% of the human genome is made up of endogenous retroviral sequences.

o Retroviruses are enveloped viruses, with an RNA genome. The name retrovirus is derived from the fact that the virus particle contains an RNA-dependent DNA polymerase – reverse transcriptase. This enzyme converts the RNA genome into DNA, which then integrates into the host chromosomal DNA. The reverse transcriptase enzyme is highly error prone and rapid genetic variation is a feature of this group of viruses.

KEY FACTS ABOUT XMRV: Xenotropic murine leukaemia virus-related virus

o XMRV is a gammaretrovirus that was first described in 2006 in a group of men who had prostate cancer.

o It may also be linked to other medical conditions, including fibromyalgia.

o XMRV is closely related to a group of retroviruses that can infect mice.

o This type of virus is thought to be transmitted through body fluids such as blood, semen and breast milk. It is not thought to be transmitted through the air – like a flu virus. But the route of transmission remains uncertain.

o Testing for evidence of the XMRV virus in blood is currently only available at a few specialised laboratories here in the UK. Demonstrating a link between a retrovirus and ME/CFS does not, by itself, resolve the physical vs psychological debate. Research studies have demonstrated links between retroviruses and diseases as diverse as autoimmune disorders (which could be relevant to ME/CFS), immunodeficiency diseases, multiple sclerosis, tumours, anaemias and even schizophrenia.

CONCLUSIONS

The bottom line to this interesting research is that it currently raises more questions than answers.

o Does the presence of XMRV in healthy people make them more likely to develop ME/CFS when another infection appears?

o Does XMRV cause ME/CFS in some cases? Or does XMRV become active as a result of having ME/CFS?

o Or is it simply an innocent bystander with no role in the illness?

o Should XMRV be treated?

When we have accurate answers to at least some of these questions we can move forward, if necessary, with testing and treatment.

We will update this summary as further information becomes available.

If you want to comment on it please do so via the MEA Website.

Dr Charles Shepherd
Hon Medical Adviser, ME Association

Summary 3 dated 4 November 2009