XMRV Retrovirus: Round up 25: WPI on DeFreitas, Hansard, MEA, AfME, Johnson
December 9, 2009
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
Whittemore Peterson Institute on Facebook
Statement posted by Whittemore Peterson Institute on 25 November under their “Notes” tab
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:
These data are indisputable that XMRV is NOT the retrovirus described by De Freitas et al.”
7 Dec 2009 : Column 46W
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. 
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
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: http://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.
Dr Charles Shepherd
Hon Medical Adviser, MEA
(This information may be forwarded if you wish to do so)
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.
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.
Action for M.E.
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
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
Commentary on research
Dr. Timothy Luckett’s blog
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.”
5 December 2009
“When did it stop being about you and become all about them?”
Websites, communities, commentary and quality forums
Dan Moricoli’s ME-CFS Community
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/
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:
Click here for all previous XMRV Round ups and postings in reverse date order: https://meagenda.wordpress.com/category/xmrv/