Official Statement from the Whittemore Peterson Institute Regarding UK Study

Official Statement from the Whittemore Peterson Institute Regarding UK Study [Imperial College London PloS ONE XMRV paper]

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

Released: 6 January 2010    

PDF: WPI Official Statement 06.01.10

Whittemore Peterson Institute for Neuro-Immune Disease

FOR IMMEDIATE RELEASE
Frankie Vigil
R&R Partners for
Whittemore Peterson Institute
775-336-4555
frankie.vigil@rrpartners.com 

Official Statement from the Whittemore Peterson Institute Regarding UK Study

The Whittemore Peterson Institute (WPI) has reviewed the paper entitled “Failure to Detect the Novel Retrovirus XMRV in Chronic Fatigue Syndrome.” This study did not duplicate the rigorous scientific techniques used by WPI, the National Cancer Institute and the Cleveland Clinic, therefore it cannot be considered a replication study nor can the results claim to be anything other than a failure not just to detect XMRV, but also a failure to suggest meaningful results.

The scientific methods used by WPI are very exact and require specific techniques to ensure accuracy. Differences in techniques employed by Erlwein et al. not only explain their failure to replicate the WPI study, but also render the conclusions meaningless. These differences include, but are not limited to the following:

1) blood sample volumes and processing;
2) patient criteria/population differences;
3) number and type of tests done to assure accurate results, including white blood cell culture;
4) use of a molecular plasmid control in water versus a positive blood sample; and
5) different primer sequences and amplification protocol used to find the virus, which were not validated by a clinical control.

The WPI study was published after six months of rigorous review and three independent lab confirmations, proving that contamination had not taken place and that infectious XMRV was present in 67 percent of CFS patients diagnosed according to the Canadian and Fukuda criteria.

In contrast, this latest study was published online after only three days of review. Significant and critical questions remain as to the status of patient samples used in the UK study as those samples may have been confused with fatigued psychiatric patients, since the UK has relegated “CFS” patients to psychiatric care and not traditional medical practices.

“Little is known about the prevalence of XMRV world-wide, much less the incidence of XMRV in ME/CFS or prostate cancer” emphasizes Dr. Judy Mikovits. “WPI and its NCI collaborators are actively engaged with international research teams to investigate these important questions.”

WPI does not recommend the use of anti-retroviral drugs that have yet to be proven to be effective in treating XMRV infection. However, several large pharmaceutical companies have expressed interest in developing anti-retroviral and immune modulating drugs that will effectively treat XMRV associated diseases.

WPI looks forward to the results of other scientific groups around the world, serious about replicating its scientific results, by using the same techniques as WPI and its collaborators. The fact that XMRV was detected in 67 percent of the CFS samples in the U.S. study determined a significant association between XMRV and CFS, demanding a much more serious inquiry by responsible health agencies around the world as to the cause of this debilitating disease

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

XMRV retrovirus replication: Round up 3

XMRV retrovirus replication: Round up 3: NHS Choices; CFIDS news release; Neuroskeptic blog

Abstract and links for full paper here: http://wp.me/p5foE-2Bd
Media coverage Round up 1 here: http://wp.me/p5foE-2Bj
Patient organisation responses Round up 2 here: http://wp.me/p5foE-2BA

Shortlink for this posting: http://wp.me/p5foE-2Ci

Media coverage

NHS Choices  |  6 January 2010

UK NHS Choices site

Virus link to CFS ‘in doubt’

“Serious doubt has been cast on the theory that…chronic fatigue syndrome is caused by a new retrovirus,” The Guardian reported. The newspaper said researchers from London have failed to replicate findings from the US that suggested a possible role for a virus called XMRV in causing CFS, also known as ME (myalgic encephalomyelitis).

In the new study none of the 186 UK CFS patients tested carried the XMRV virus, in contrast to the US study in 2009, which found that about two-thirds of 101 CFS patients tested had the virus. Why the two studies have different findings is not clear, but the results of the UK study do not support an association between XMRV infection and CFS in UK patients. This highlights the importance of different research groups repeating experiments in different populations.

CFS is a complex disease, and its causes are not well understood. Although an association with XMRV has not been established, this does not rule out the possibility that viral infection is involved. Much more research will be needed in this area.

Where did the story come from?

The research was carried out by Dr Otto Erlwein and colleagues from Imperial College London and King’s College London. The researchers were funded by the South London and Maudsley NHS Foundation Trust, the Institute of Psychiatry and the National Institute for Health Research Biomedical Research Centre. The study was published in the peer-reviewed open access journal PLoS ONE.

The Guardian, Daily Mail and The Independent reported the story. In general, the coverage is balanced and accurate. The headline of the Daily Mail story that “British experts say ME virus is a myth” might be taken to mean that this research excludes any role for viral infection in CFS/ME, but this research only looked at one virus (XMRV).

What kind of research was this?

This cross-sectional study investigated whether people in the UK with chronic fatigue syndrome (CFS) were infected with the xenotropic murine leukaemia virus-related virus (XMRV). In 2009, a case control study from the US found that more people with CFS carried the virus than people without the condition. The researchers in this study wanted to see if XMRV was similarly common in people from the UK with CFS.

A cross-sectional study design is appropriate for determining how common a particular trait is among a certain group of people. However, neither this study, not the original case-control study could prove whether XMRV potentially caused CFS, as neither would be able to establish whether people with XMRV had been infected before they developed CFS or after. The current study would also not have been able to say whether the XMRV virus was more or less common in people with CFS than in those without it, as it did not include a control group of people without the disease.

What did the research involve?

The researchers enrolled 186 people with CFS who were living in the UK. These people had been medically examined and diagnosed with CFS according to standard criteria, and other potential causes of their symptoms had been ruled out. Blood samples were taken and tested for the presence of DNA from XMRV or a related virus called murine leukaemia virus (MLV). A number of control tests were also carried out to show that the DNA in these samples was intact, that any positive findings were not a result of contamination of their experiment and that their test would identify XMRV if it was present. The inclusion of these controls is important for ensuring that the experiments were working well and were reliable. The researcher who carried out the DNA tests did not know which of the samples came from people with CFS.

The participants, all of whom had been referred to a CFS clinic, were mainly female (62%) with an average age of 39.6 years. They had been unwell for an average (median) of four years (range one to 28 years), and had high levels of fatigue. Few participants were working and about a fifth (19%) belonged to CFS/ME support groups. Just under half of the participants (45%) said that their CFS definitely related to a viral infection and 45% said that it might relate to a viral infection. The researchers suggested that the characteristics of their sample were typical of those seen in CFS patients attending specialist clinical services in the UK.

What were the basic results?

The researchers did not identify XMRV or MLV in the blood from any of the 186 CFS patients tested. Their control tests showed that the DNA being tested was intact, that there was no contamination in their experiments and that when XMRV was present (in a positive control sample containing XMRV DNA) their test detected it.

How did the researchers interpret the results?

The researchers concluded that they “found no evidence that XMRV is associated with CFS in the UK”. They suggested that the reason for the differences between their findings and those from the US might be due to differences in how common XMRV infection is in the different countries.

Conclusion

This study suggests that the XMRV infection is not common in CFS patients in the UK. A previous case-control study from the US found that about two-thirds of the 101 CFS patients tested carried XMRV, compared to about 4% of 218 healthy controls. This led the researchers from the US study to suggest that XMRV might be the cause of CFS in these patients. The reason for the differences between the US and UK studies is not clear, but the authors of the UK study suggest that it could be due to XMRV infection being more common in the US than in Europe.

The findings of this current study highlight the importance of different research groups repeating experiments in different populations. The study does have some limitations in that it was relatively small and all participants came from one CFS centre in London. Further studies in more participants from different centres in the UK would be useful in determining whether these findings are typical of the UK as a whole.

Even if this study had found significant levels of XMRV in CFS patients, it would not have been able to prove the virus actually caused the condition. This is because, like the original US case-control study, it could not establish whether people with XMRV had been infected before they developed CFS or after.

The current study would also not have been able to say whether the XMRV virus was more or less common in people with CFS than those without, as it did not include a control group of people without the disease.

The results of this UK study do not support an association between the XMRV virus and CFS in UK patients. The researchers do not rule out a role for all viruses in CFS, and say that “prospective epidemiological studies have confirmed that certain infective agents, for example Epstein Barr virus, are unequivocally associated with subsequent CFS, even if the mechanisms are unclear and almost certainly multi factorial”. CFS is a complex disease, and its causes are not well understood. Much more research will be needed in this area.

Links to the headlines

Research casts doubt over US chronic fatigue virus claim. The Guardian, January 06 2010
British experts dash ME breakthrough hopes following American promise of new treatment. Daily Mail, January 06 2010
Scientists’ claim to have found the cause of ME is ‘premature’. The Independent, January 06 2010

Links to the science

Erlwein O, Kaye S, McClure MO, et al. Failure to Detect the Novel Retrovirus XMRV in Chronic Fatigue Syndrome. PLoS ONE, 2010; 5/

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Patient advocacy organisations

CFIDS Association of America   |  6 January 2010

CFIDS Association of America Expresses Concerns About UK XMRV Replication Study

Additional and More Rigorous Research Needed

CHARLOTTE, N.C. (January 6, 2009) – The CFIDS Association of America issued the following statement in response to a study published in today’s edition of PLoS ONE that failed to detect the XMRV virus in banked samples drawn from 186 CFS patients in the United Kingdom. A study published Oct. 8, 2009 in Science reported that 68 of 101 CFS patients from clinics in the U.S. tested positive for XMRV.

“The CFIDS Association of America reviewed the study published in today’s edition of PLoS ONE. We are concerned about many elements of this study including differences between the patients selected by the two groups, different processes used to collect and test the blood samples, and the rapid nature of the new publication, as evidenced by the three days that separated the dates of submission and acceptance,” stated K. Kimberly McCleary, president and CEO of the CFIDS Association of America. “We urge the media and the research and patient communities to view these findings in the context of evolving understanding and to insist upon more rigorous and standardized replication studies before drawing conclusions about the role of XMRV in the pathophysiology of CFS.”

CFIDS Association scientific director Suzanne D. Vernon, PhD, made the following assessment: “The new report from the U.K. should not be considered a valid attempt to replicate the findings described by Lombardi, et al., in the Science article. This paper heavily underscores the need for expedient, yet robust, XMRV-focused research to build upon the results reported this past fall, studies like the one being conducted by the Department of Health and Human Services Blood XMRV Scientific Research Working Group.” Vernon holds her doctorate in virology from the University of Wisconsin and had 17 years experience in public health research on infectious diseases before joining the Association’s staff in 2007 to lead its research program. She added, “Without a standardized method of detecting XMRV, millions of dollars might be wasted on independent attempts to determine the prevalence of XMRV in different populations.”

“Every person whose life has been impacted by CFS wants urgently to identify the cause of and a cure for this devastating condition that affects millions of people worldwide. While time is of the essence, we must insist upon rigorously conducted and reviewed science that provides absolute validation, definitive answers and unbridled hope,” said McCleary.

The CFIDS Association of America is the nation’s largest charitable organization dedicated to making CFS widely understood, diagnosable, curable and preventable. It is the greatest source of funding for CFS research outside the federal government. To view Dr. Vernon’s detailed analysis of the U.K. study, please visit

http://www.cfids.org/cfidslink/2010/010603.asp

Citations:
Erlwein O, Kaye S, McClure MO, Weber J, Willis G, Collier D, Wessley S, Cleare A. (2010) Failure to detect the novel retrovirus XMRV in chronic fatigue syndrome. PLoS ONE 5(1):e8519. doi:10.1371/journal.pone.0008519

Lombardi VC, Ruscetti FW, Gupta JD, Pfost MA, Hagen KS, Peterson DL, Ruscetti SK, Bagni RK, Petrow-Sadowski C, Gold B, Dean M, Silverman RH, Mikovits JA. Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome. Science 8 October 2009. 1179052.

Science Bloggers

Neuroskeptic  | 6 January

Chronic Fatigue Syndrome in “not caused by single virus” shock!

Imperial College London News Release 06.01.10

Imperial College London NEWS RELEASE 06.01.10

Abstract and links for full paper here: http://wp.me/p5foE-2Bd
Media coverage Round up 1 here: http://wp.me/p5foE-2Bj
Patient organisation responses Round up 2 here: http://wp.me/p5foE-2BA

Shortlink for this posting: http://wp.me/p5foE-2BT

Imperial College London News Release

On the ICL website

Open PDF: Imperial College London News Release XMRV

Wednesday 6 January 2010

New virus is not linked to Chronic Fatigue Syndrome, suggests UK research

New UK research, published today in PLoS ONE, has not reproduced previous findings that suggested Chronic Fatigue Syndrome may be linked to a recently discovered virus. The authors of the study, from Imperial College London and King’s College London, say this means that anti-retroviral drugs may not be an effective treatment for people with the illness.

An estimated three in 1000 people have Chronic Fatigue Syndrome (CFS), or myalgic encephalomyelitis (ME), experiencing severe physical and mental fatigue that is not alleviated by rest, together with other symptoms such as muscle pain, headache, joint pain and depression. Diagnosing CFS is difficult, as symptoms vary and there is no standard test. The fundamental cause of CFS is unknown and it is usually treated using rehabilitation techniques such as cognitive behavioural therapy or graded exercise therapy.

In October 2009, a group of US scientists published research in the journal Science that suggested that a recently discovered virus called XMRV could be linked to CFS. In their study, 68 out of 101 patients with the illness and 8 out of 218 healthy controls appeared to be infected with the virus.

However, in today’s study, researchers found no evidence that patients with CFS had the XMRV virus, after analysing tissue samples from 186 patients with CFS using sensitive molecular testing techniques.

This more recent analysis showed no molecular evidence for XMRV in any of the samples from CFS patients. The researchers say this means that anti-retrovirals should not be used to treat CFS, as they would be unlikely to have an effect on the symptoms. However, several labs in the US now offer CFS  patients treatments based on the earlier findings that linked the condition with XMRV.

Professor Myra McClure, one of the authors of the study from the Division of Medicine at Imperial College London, said: “Our research was carried out under rigorous conditions – we looked at samples from well-studied patients, and we used very sensitive testing methods to look for the virus. If it had been there, we would have found it. The lab in which we carried out the analysis had never housed any of the murine leukaemia viruses related to XMRV, and we took great care to ensure there was no contamination.

“We are confident that our results show there is no link between XMRV and Chronic Fatigue Syndrome, at least in the UK. The US study had some dramatic results that implied people with the illness could be treated with anti-retrovirals. Our recommendation to people with Chronic Fatigue Syndrome would be not to change their treatment regime, because our results suggest that anti-retrovirals would not be an effective treatment for the condition,” added Professor McClure.

After reading the US study, clinical researchers from King’s College London sent blood samples from 186 CFS patients to the Imperial Retrovirology Laboratory team. King’s has been running an NHS service for CFS patients for nearly twenty years, and the previously stored samples came from patients had been fully investigated and examined, meaning that CFS was the correct diagnosis.

The Imperial scientists extracted the DNA from the samples and analysed it using a sensitive technique, called Polymerase Chain Reaction (PCR), which can locate tiny fragments of virus DNA. The scientists analysed control samples of water at the same time to ensure there was no contamination. They also looked for a specific marker fragment of human DNA in the sample to make sure the technique was working.

The water controls contained no DNA, showing that the samples were not contaminated. All the test samples, from patients and healthy controls, contained the human DNA they looked for, suggesting the technique was working well.

Dr Anthony Cleare, Reader in Psychiatric Neuroendocrinology, one of the authors of the study from the Chronic Fatigue Syndrome Clinic at King’s College London, said: “Chronic Fatigue Syndrome is a serious and debilitating condition. It can also be extremely frustrating for people with the illness, as we have yet to identify its  fundamental cause, or come up with any definitive treatments. The recent US study generated real excitement among doctors and patients alike as it seemed to open up a new line of research. Unfortunately, we have not been able to replicate those findings.”

“It is important to emphasise that today’s findings do not invalidate all previous research, some of which has shown that CFS can be triggered by other infective agents, such as Epstein Barr Virus or Giardia parasites. As ever in science, no single study is conclusive and there are lots of other research groups working on this at the moment. We await their results with interest,” added Professor Simon Wessely, another author of the study from the Chronic Fatigue Syndrome Clinic at King’s College London.
-Ends-

Notes to Editors:
1. “Failure to Detect the Novel Retrovirus XMRV in Chronic Fatigue Syndrome” PLoS ONE, Wednesday 6 January 2010.

XMRV retrovirus replication: Round up 2 Patient org responses

XMRV retrovirus replication: Round up 2 Patient organisation responses

Abstract and links for full paper here: http://wp.me/p5foE-2Bd
Media coverage Round up 1 here: http://wp.me/p5foE-2Bj
Patient organisation responses Round up 2 here: http://wp.me/p5foE-2BA

Shortlink for this posting: http://wp.me/p5foE-2BA

Patient representation organisation statements

UK patient organisations

Action for M.E.  |  6 January 2010

News

Link between XMRV and CFS?

New UK research claims there’s no link between XMRV and CFS.

Research published today from Imperial and King’s College London announces that they have been unsuccessful in finding the XMRV retrovirus in a sample of British patients with chronic fatigue syndrome.

Last year, as reported on our website, the Whittlemore Peterson Institute in America found that 68 out of 101 patients with the illness appeared to be infected with the virus, compared to 8 out of 218 healthy controls.

The recent UK study analysed tissue samples from 186 patients with CFS using sensitive molecular testing techniques, but found no evidence that they had the XMRV virus.

In a press release issued by Imperial College, Professor Myra McClure, one of the authors of the study, said:

“Our research was carried out under rigorous conditions – we looked at samples from well-studied patients, and we used very sensitive testing methods to look for the virus. If it had been there, we would have found it. The lab in which we carried out the analysis had never housed any of the murine leukaemia viruses related to XMRV, and we took great care to ensure there was no contamination.

“We are confident that our results show there is no link between XMRV and Chronic Fatigue Syndrome, at least in the UK. The US study had some dramatic results that implied people with the illness could be treated with anti-retrovirals. Our recommendation to people with Chronic Fatigue Syndrome would be not to change their treatment regime, because our results suggest that anti-retrovirals would not be an effective treatment for the condition,” added Professor McClure.

Sir Peter Spencer, Action for M.E. says:

“Action for M.E. is disappointed to hear about these findings but no single small-scale study can be conclusive and the fact remains: American researchers found XMRV virus in 68 out of 101 people with chronic fatigue syndrome. Were those samples contaminated – or were those people susceptible to XMRV because they had CFS?

“What we need is more research involving large numbers of carefully characterised patients at a number of sites, preferably using fresh, not stored, blood samples. We also need studies on large numbers of both healthy people and people with other conditions.

“250,000 British men, women and children have this devastating illness. They need answers, better treatments and a cure.”

Note: Imperial College London Press Release

ME Association  |  6 January 2010

ME Association statement – XMRV: UK research group fails to replicate American findings

Failure to detect the novel retrovirus XMRV in chronic fatigue syndrome.

Erlwein O et al. Public Library of Science/PLoS ONE open access journal: January 2010.

In October 2009, an American research group published a paper in Science which reported that they had found evidence of a new retrovirus called XMRV (xenotropic murine leukaemia virus-related virus) in a very high percentage (68/101) of people with ME/CFS – whose diagnosis met with both 1994 CDC/Fukuda research criteria and the Canadian clinical criteria. This compared to only 8/218 positive tests in the healthy controls.

The MEA has provided regular website updates on these findings and offered to help fund further research studies which would attempt to replicate these findings. Our latest XMRV update can be found here.

A number of research groups both here and abroad are now carrying out XMRV replication studies using stored blood samples.

The first study to be reported in the medical literature comes from a very reputable virology/infectious disease group at Imperial College in London. The group obtained stored blood samples from patients who have been attending the King’s College Hospital ME/CFS service.

The virologists examined 186 blood samples from the KCH patients who met Fukuda/CDC criteria for CFS using sensitive molecular testing techniques. DNA (viral genetic material), which was extracted from the blood samples, was screened for XMRV provirus and for the closely related murine leukaemia virus (MLV) by nested PCR (polymerise chain reaction)using specific oligonucleotide primers. PCR is a highly sensitive method that can locate tiny viral fragments. No molecular evidence of XMRV or MLV sequences was found in any of the ME/CFS samples.

These results clearly represent a major difference in scientific opinion on the possible role of XMRV in ME/CFS.

Among the explanations that could be relevant are:

1 The use of different types of ME/CFS patients in the two studies. The American patients had ‘severe disability’, were diagnosed using both CDC/Fukuda and Canadian clinical criteria, and were obtained from a small group of private physicians who take a very biomedical approach to ME/CFS. The UK sample, who had ‘high levels of disability’, were diagnosed using only Fukuda/CDC criteria and came from King’s College Hospital in London – an NHS tertiary referral centre that specialises in behavioural interventions.

2 There may be different prevalence rates for XMRV in different countries and it is interesting to note that German researchers were unable to replicate the American results in relation to the presence of XMRV in patients with prostate cancer.

3 The UK and USA laboratories used slightly different techniques for investigating the presence of XMRV and there may have been differing levels of risk in relation to the possibility of laboratory XMRV contamination.

Comment from Dr Charles Shepherd, honorary medical adviser to the ME Association:

“The ME Association has taken a cautious and open-minded view about the initial XMRV findings and offered to help fund further research into what could be a very significant finding. Although these UK results are clearly questioning the validity of the American findings, no single study can be regarded as being conclusive. So we believe it is important to wait for the results of further replication studies before drawing any firm conclusions about the possible role or pathogenicity (disease-causing ability) of XMRV in ME/CFS. In the meantime, there seems little point in people with ME/CFS spending large sums of money in arranging private tests for XMRV. And in our current state of uncertainty it would not be appropriate for doctors to start prescribing antiretorviral treatment to people with ME/CFS”.

Invest in ME  |  6 January 2010

STATEMENT by INVEST in ME

BBC NEWS ARTICLE “Research finds no proof that a virus is the cause of ME”

The perennial problem of trials such as this from ICL and those funded by the Medical Research Council is that they do not use well defined patient cohorts which can negate the research results.

To replicate a research study the patient samples used and the methodology have to be the same and in this case it appears that there are differences in both compared to the study published online 8 October, 2009 by the Science magazine.

The organisations in USA who discovered the XMRV retrovirus used the Canadian Guidelines to select patients for their research and Invest in ME feel the Canadian Guidelines should be used for all research.

Those who portray ME as a somatoform illness are fully aware that using patients who do not fit strict selection criteria will obviously skew results. We therefore have serious doubts about the the results of the ICL research.

If the correct patient cohorts are not participating in the trials or different methods are used then this will affect the results.

The result of finding no sign of XMRV would point to a different methodology to that used in the research published by the Science magazine in which 3.7% of controls tested positive.

The work performed by the Whittemore-Peterson Institute (WPI) and the National Cancer Institute and the Cleveland Clinic is of the highest quality and has been validated by Science magazine.

Much more research is underway and the results from the first XMRV replication trials such as these from ICL prove little.

People with ME and their families should expect these “false” results to be publicised early, especially as ME has been ignored by the government and research organisations for generations. However, the new XMRV research has changed the landscape for good and patients and carers can look forward to a new era of ME/CFS research based on the biomedical basis for the illness.

Proper science is now finally being performed.

Those who have delayed or stopped high quality biomedical research into ME from being performed in the past, and those who continue to downplay the significance of the new research from WPI, will not be in a position to continue this denial for much longer.

The WPI have promised more exciting news which we can expect to hear at the forthcoming 5th Invest in ME International ME/CFS Conference on 24th May in London.

Invest in ME remain convinced that the WPI research is of monumental importance to the future of research into ME and we look forward to the future and the momentum in biomedical research into ME which the XMRV research has generated.

Invest in ME
www.investinme.org

The BBC article is available – click here

The PLoS One article is here

Further links:

Documented involvement of Viruses in ME/CFS
5th Invest in ME International ME/CFS Conference 2010
The Proof is Out There – the WPI research – click here

US patient organisations

CFIDS Association of America  |  6 January 2010

XMRV Negative Results Emphasize Need for Robust Replication Study

Suzanne D. Vernon, PhD
Scientific Director

A study testing for evidence of XMRV infection in CFS patients in the United Kingdom has reported negative results. This is the first publication following the article in the top-ranked journal Science from researchers at the Whittemore Peterson Institute, the National Cancer Institute and Cleveland Clinic that garnered worldwide attention from the media and scientific community. The new report, published Jan. 6, 2010, in the open access online journal PLoS ONE, failed to detect XMRV in CFS, but should not be considered a valid attempt to replicate the findings described by Lombardi et al., in the Oct. 8, 2009 Science article.

The PLoS ONE paper by Otto Erlwein, Steve Kaye, Myra O. McClure, Jonathan Weber, Gillian Wills, David Collier, Simon Wessely and Anthony Cleare is titled, “Failure to Detect the Novel Retrovirus XMRV in Chronic Fatigue Syndrome.” The investigators tested peripheral blood DNA from 186 routine clinic attendees who met 1994 (Fukuda) CFS case definition criteria and were well-characterized from participation in prior neuroendocrine and cognitive behavioral therapy studies. These 186 CFS patients were reported to be unwell for a median of four years with high levels of fatigue and disability.

This team of researchers used a special type of DNA “xeroxing” called nested polymerase chain reaction (PCR) reaction to amplify specific segments of the XMRV proviral DNA from the genomic DNA obtained from these 186 CFS subjects. In essence, they were looking to see if XMRV genetic material had integrated into human genetic material, which is a key characteristic of retroviral infection. The experiment included positive, negative and contamination controls, but did not test any samples taken from healthy subjects. The samples were coded so that the origin of the DNA was not known to the person conducting the PCR assays. XMRV was not detected in any of the 186 samples.

Can this study be considered comparable to the results published by Lombardi et al., in Science? In short, no. Both studies included CFS patients defined by the 1994 case definition criteria, but this is where the comparability ends. Here are some of the ways the PLoS ONE and Science methods differ:

The blood was collected from CFS patients in different types of blood collection tubes.
The genomic DNA was extracted and purified using different techniques.
The amount of genomic DNA included in the amplification assay was different.
Different primer sequences were used that amplified different regions of the XMRV proviral DNA.
The conditions of the PCR amplification assay were different – from the numbers of cycles, to the type of polymerase used.
Should these differences affect an investigator’s ability to detect XMRV? To a microbiologist with experience handling samples and studying various infectious agents (as I am), these variances in procedure could make the difference between detecting XMRV or not.

It very well could be true that XMRV is not present in the U.K. as Erlwein, et al. suggest in their discussion, but it is also possible that the technique used in the PLoS ONE paper was suboptimal due to the different methods employed, when compared to the original experiments conducted by Lombardi, et al.

The U.S. Department of Health and Human Services Blood XMRV Scientific Research Working Group is conducting a rigorous study to detect XMRV. Multiple laboratories will standardize methods to optimize sensitive detection of XMRV proviral DNA and viral RNA and then, once methods are standardized, these same laboratories will test coded panels of blood samples obtained from healthy blood donors and CFS patients. We look forward to the results of this study and urge that it be completed expeditiously, especially in light of this report from the U.K. In the meantime, be prepared to read about more studies with conflicting findings. Rather than simply accept or dismiss new information, we will help make sense of why discrepant results occur.

Perhaps the most important statement in the PLoS ONE paper is the acknowledgement by this group of investigators that CFS is an incapacitating organic disease affecting millions of people worldwide. Once XMRV detection methods are optimized and made widely available, we encourage this group of researchers to take another look at XMRV as a possible explanation for the organic basis of CFS in the U.K.

Citations:
Erlwein O, Kaye S, McClure MO, Weber J, Willis G, Collier D, Wessley S, Cleare A. (2010) Failure to detect the novel retrovirus XMRV in chronic fatigue syndrome. PLoS ONE 5(1):e8519. doi:10.1371/journal.pone.0008519

Lombardi VC, Ruscetti FW, Gupta JD, Pfost MA, Hagen KS, Peterson DL, Ruscetti SK, Bagni RK, Petrow-Sadowski C, Gold B, Dean M, Silverman RH, Mikovits JA. Detection of an infectious retrovirus, XMRV, in blood cells of patients with chronic fatigue syndrome. Science 8 October 2009. 1179052.

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Suzanne D. Vernon, PhD, earned her doctorate in virology at the University of Wisconsin at Madison and worked in public health research on infectious diseases at the U.S. Centers for Disease Control and Prevention for 17 years before joining the CFIDS Association of America’s staff as scientific director in 2007. She has more than 70 peer-reviewed scientific publications on topics including human immunodeficiency virus, human papillomavirus, cervical cancer and chronic fatigue syndrome. Dr. Vernon has initiated and participated in numerous international and multidisciplinary research collaborations and she now leads the CFIDS Association’s research program. The CFIDS Association of America is the nation’s largest philanthropic supporters of CFS research.

Advocacy commentary

Dan Moricol’s ME-CFS Community Network 

Cort Johnson’s Phoenix Rising website

The XMRV Buzz! – the Latest News on XMRV

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The Fight is on…Imperial College XMRV Study

XMRV retrovirus replication: Round up 1

XMRV retrovirus replication: Round up 1

Abstract and links for full paper here: http://wp.me/p5foE-2Bd
Media coverage Round up 1 here: http://wp.me/p5foE-2Bj
Patient organisation responses Round up 2 here: http://wp.me/p5foE-2BA

Shortlink for this posting: http://wp.me/p5foE-2Bj

Media coverage

The Guardian  |  Sarah Boseley  |  6 January 2010

Research casts doubt over US chronic fatigue virus claim
     UK study fails to find proof of headline-grabbing American study into test for ME/CFS

Ed: Note that in 2001, the Guardian’s Sara Boseley had reported:

“Prof Wessely has quit the field – and is not the only professional to have ceased involvement with CFS.”
        Storm brews over ‘all in mind’ theory of ME, Guardian, 20 September 2001

A week later in the Guardian, Ms Boseley wrote:

“Simon Wessely, of the Department of Psychological Medicine at Guy’s, King’s and St Thomas’s School of Medicine in London, is a former key figure in the study of ME/CFS who has felt the heat and largely backed out of the kitchen.” 
        A very modern epidemic, Guardian, 27 September 2001

But just like the Energizer Bunny, Professor Wessely keeps on going…

Whilst on the Guardian site, I was discomforted to see that the Guardian evidently considers its readership so lacking in gumption and basic needlework skills that it has published an article with step by step instructions on How to make a draught excluder and having stuffed it, how to pimp your draught excluder so it looks like a snake…

Optional: To make a snake draught excluder, simply sew on two buttons for eyes and a piece of red ribbon (with a V-shaped piece cut out of one end) for a forked tongue.

It’s an ill wind… 

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New Scientist  |  Clare Wilson and Ewen Callaway  |  6 January 2010

CFS patients in UK show no signs of suspect virus

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Daily Mail  |  Fiona Macrae  |  6 January 2010

British experts say ME virus is a myth

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Independent   |  Steve Connor   |  6 January 2010

Researchers must work together

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Science Daily   |  6 January 2010

New Virus Is Not Linked to Chronic Fatigue Syndrome, Suggests New Research

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e! Science News  |  5 January 2010

New virus is not linked to chronic fatigue syndrome, suggests UK research

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BBC News  |  Michelle Robertsm Health reporter  | 5 January 2010

Research finds no proof that a virus is the cause of ME

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Additional reporting, today, will be added to the top of this posting.

Abstract paper: Failure to Detect the Novel Retrovirus XMRV in Chronic Fatigue Syndrome

Abstract paper: Failure to Detect the Novel Retrovirus XMRV in Chronic Fatigue Syndrome

Abstract and links for full paper in this posting: http://wp.me/p5foE-2Bd
Media coverage Round up 1 here: http://wp.me/p5foE-2Bj
Patient organisation responses Round up 2 here: http://wp.me/p5foE-2BA

Abstract and access to full paper in text and PDF format on PLoS ONE site here:

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0008519

or open PDF here: Imperial College London study

Failure to Detect the Novel Retrovirus XMRV in Chronic Fatigue Syndrome

Otto Erlwein1, Steve Kaye1, Myra O. McClure1*, Jonathan Weber1, Gillian Wills1, David Collier2, Simon Wessely3, Anthony Cleare3

1 Jefferiss Research Trust Laboratories, Section of Infectious Diseases, Wright-Fleming Institute, Faculty of Medicine, Imperial College London, St Mary’s Campus, Norfolk Place, London, United Kingdom, 2 Social Genetic and Developmental Psychiatry Centre, Institute of Psychiatry (King’s College London) De Crespigny Park, Denmark Hill, London, United Kingdom, 3 Department of Psychological Medicine, Institute of Psychiatry, King’s College London, Camberwell, London, United Kingdom

Background

In October 2009 it was reported that 68 of 101 patients with chronic fatigue syndrome (CFS) in the US were infected with a novel gamma retrovirus, xenotropic murine leukaemia virus-related virus (XMRV), a virus previously linked to prostate cancer. This finding, if confirmed, would have a profound effect on the understanding and treatment of an incapacitating disease affecting millions worldwide. We have investigated CFS sufferers in the UK to determine if they are carriers of XMRV.

Methodology

Patients in our CFS cohort had undergone medical screening to exclude detectable organic illness and met the CDC criteria for CFS. DNA extracted from blood samples of 186 CFS patients were screened for XMRV provirus and for the closely related murine leukaemia virus by nested PCR using specific oligonucleotide primers. To control for the integrity of the DNA, the cellular beta-globin gene was amplified. Negative controls (water) and a positive control (XMRV infectious molecular clone DNA) were included. While the beta-globin gene was amplified in all 186 samples, neither XMRV nor MLV sequences were detected.

Conclusion

XMRV or MLV sequences were not amplified from DNA originating from CFS patients in the UK. Although we found no evidence that XMRV is associated with CFS in the UK, this may be a result of population differences between North America and Europe regarding the general prevalence of XMRV infection, and might also explain the fact that two US groups found XMRV in prostate cancer tissue, while two European studies did not.

Citation: Erlwein O, Kaye S, McClure MO, Weber J, Wills G, et al. (2010) Failure to Detect the Novel Retrovirus XMRV in Chronic Fatigue Syndrome. PLoS ONE 5(1): e8519. doi:10.1371/journal.pone.0008519

Editor: Douglas F. Nixon, University of California San Francisco, United States of America

Received: December 1, 2009; Accepted: December 4, 2009; Published: January 6, 2010

Copyright: © 2010 Erlwein et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: AC, DC and SW are partially funded by the South London and Maudsley NHS Foundation Trust/Institute of Psychiatry National Institute of Health Biomedical Resaerch Centre. The team from Imperial College is grateful for support from the NIHR Biomedical Research Centre Funding Scheme. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.

* E-mail: m.mcclure@imperial.ac.uk

Full paper, tables and references here, published under “Open Access:

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0008519

BBC: Research finds no proof that a virus is the cause of ME

Abstract and links for full paper here: http://wp.me/p5foE-2Bd
Media coverage Round up 1 here: http://wp.me/p5foE-2Bj
Patient organisation responses Round up 2 here: http://wp.me/p5foE-2BA

Imperial College London News Release PDF: Imperial College London News Release XMRV

BBC: Research finds no proof that a virus is the cause of ME

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

Although a number of UK XMRV related studies have already been identified since the publication of the WPI study in Science, in October, this study co-authored by Prof Simon Wessely had not been publicly reported on.

Dr Jonathan Kerr, based at St. George’s University, London, is involved in several XMRV studies with Whittemore Peterson Institute researcher, Dr Judy Mikovits, and with others, including UK Dr Amalok Bansal and New York, Dr Derek Enlander.

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.”

Was Dr Charles Shepherd aware of this Wessely/McClure study? Professor Chris Mathias of Imperial College London was listed as a participant in the MRC’s December CFS/ME Research Workshop.

Psychiatrist, Professor Simon Wessely, King’s College London, has been claiming since 2001 to have quit the field of CFS research.

On 20 September 2001, the Guardian published an article by Health Editor, Sarah Boseley:

In this exceedingly emotive piece of journalism, Ms Boseley had reported:

“Prof Wessely has quit the field – and is not the only professional to have ceased involvement with CFS.”
        Storm brews over ‘all in mind’ theory of ME, Guardian, 20 September 2001

Just a week later in the Guardian, Ms Boseley wrote:

“Simon Wessely, of the Department of Psychological Medicine at Guy’s, King’s and St Thomas’s School of Medicine in London, is a former key figure in the study of ME/CFS who has felt the heat and largely backed out of the kitchen.” 
        A very modern epidemic, Guardian, 27 September 2001

More recently, in November 2006, the Group on Scientific Research into ME (GSRME) reported:

“[...] Wessely gave up the [CFS] research side of his work…”
        Report of the GSRME: Page 19, Section 3.2 Other Evidence We Received: Prof Simon Wessely

In November 2009, Professor Wessely wrote to an enquirer:

“…I also do very little these days around CFS – I still see patients every week, and I keep reasonably abreast of the literature, but it hasn’t been my main interest now for many years.” 

Since 2002, Professor Wessely has published around 30 papers and articles on CFS and is also an adviser on the design and execution of the MRC funded PACE Trial.

 

Click here for Archive for XMRV media coverage and related material

 

BBC News

Research finds no proof that a virus is the cause of ME

http://news.bbc.co.uk/1/hi/health/8441491.stm

Tuesday 5 January 2010

By Michelle Roberts
Health reporter, BBC News

UK scientists say they can find no proof that a particular virus is the cause of chronic fatigue syndrome (CFS) or ME, contrary to recent claims.

The Imperial College London team say they want to share the findings as some patients are pinning their hopes on drugs to fight the virus called XMRV.

They analysed blood samples from 186 patients with CFS and found none had the virus, PLoS One journal reports.

Experts said the latest findings would be a bitter disappointment to many.

They said more trials were under way and when these report in coming months, scientists will be able to draw more firm conclusions.

Work in the US, published in Science, had found the retrovirus in 68 of 101 CFS patients.

The UK team say the conflict between the two studies might be down to differences between the patients enrolled or the way the research was conducted.

“We need to be extremely cautious until we know more”
        Dr Charles Shepherd, The ME Association

Or there might be different geographical types or strains of XMRV.

Regardless, they say potent antiretroviral drugs should not be used to treat CFS because there is not enough evidence that this is necessary or helpful.

The drugs may do more harm than good, they say.

Professor Myra McClure, one of the Imperial College London investigators, said: “We are confident that our results show there is no link between XMRV and chronic fatigue syndrome, at least in the UK.”

She said they had used extremely sensitive DNA testing methods, called polymerase chain reaction, to look for the virus.

“If it had been there, we would have found it.”

‘Disappointing’

Co-author Professor Simon Wessely said the findings did not invalidate all previous research, some of which has shown that CFS can be triggered by other infectious agents, such as Epstein Barr Virus.

The charity Action for ME said it was disappointing to hear about these findings, but said no single small-scale study could be conclusive.

Dr Charles Shepherd, of The ME Association, said it was important to remain open-minded.

“We need to be extremely cautious until we know more. There has been enormous interest in this from patients.

“Some have been led into believing the cause and a test has been discovered and that treatment is just round the corner and that is not the case.

“Over the next few weeks and months we will have more results and then we can come to a conclusion.

“If it turns out that XMRV is important, we will have to start looking at whether it is worthwhile testing for it and treating it.”

ME FACTS
Causes chronic fatigue and muscle pain
Impairs immune system
Does not improve with sleep
Affects more women than men
A controversial condition that some have doubted as a genuine physical illness

Kathleen (Kay) Gilderdale 12 January court appearance: 1

Kathleen (Kay) Gilderdale 12 January court appearance: 1

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

freefoto
Postings on ME agenda site for media coverage of the death of Lynn Gilderdale and legal case are identified by the Freefoto.com image above and are archived in Categories under Gilderdale case

Update: I am advised that the case is likely to be held Court room 1 at the Lewes Combined Court. Most likely heard from 10.00 am or 10.30 am but the times will not be confirmed until the day before.

Please check the court website page that lists court hearings, on 11 January, for timings: http://www.hmcourts-service.gov.uk/cms/courthearings.htm

Kathleen (Kay) Gilderdale, whose daughter Lynn died in December 2008, will be appearing at Lewes Crown Court on 12 January 2010.

Kay will be wearing a white carnation in her lapel and has requested that those attending the court do likewise to show solidarity.

ME agenda is not able to respond to enquiries about the case from members of the public or the media. Enquiries in relation to attending the court appearance on 12 January are best directed to Dr John Greensmith of ME Free For All but any information that becomes available will be published here.

Dr John H Greensmith
drjohngreensmith@mefreeforall.org
ME Free For All

Lynn’s experience of living with ME had been published by the Mail in 2006:

http://www.dailymail.co.uk/health/article-393915/Trapped-bed-14-years-chronic-fatigue.html

and also by the BBC in 2001:

http://news.bbc.co.uk/1/hi/health/1234297.stm 

For many years, Lynn had been the “face” of the 25% ME Group

25% M.E. Group Statement 

Lynn Gilderdale

Statement

http://www.25megroup.org/News/news.htm

Kay Gilderdale Support Fund

http://www.25megroup.org/News/Kay%20Gilderdale%20support%20fund.doc

 

Dr Macintyre and the Gilderdale family discuss ME

News at Ten 
16/04/09

Channel 4 news, 7pm
16/04/09

ITN news, 10pm
16/04/09

Click here for all previous coverage of the Gilderdale family’s case. The 24 postings are archived in reverse date order:

Gilderdale case archive on ME agenda

visiNew Year, new look

New Year, new look

Give it a few days and you’ll love it…

I have also launched a companion site to ME agenda

Dx Revision Watch

http://dxrevisionwatch.wordpress.com

Why another site?

The concept for Dx Revision Watch developed out of research and awareness raising undertaken throughout 2009 around the forthcoming revisions of two important international disease classification systems:

The American Psychiatric Association’s Diagnostic and Statistical Manual (DSM)

The World Health Organisation’s International Statistical Classification of Diseases and Related Health Problems (ICD)

DSM-5 and ICD-11 Watch will distil information already published on ME agenda site around the two revision processes and present this material in a more accessible format to a wider audience. Key information and resources will be added as more information becomes available. Updates will be posted on the rolling “Main Page”.

Read on here

DSM-5 and ICD-11 Watch: Monitoring the progress of the DSM and ICD revision processes

 

The next edition of the APA’s Diagnostic and Statistical Manual will be DSM-5 (DSM-V). DSM-5 is now expected to be published in May 2013 – a year later than had previously been planned.

Draft changes to the DSM are expected to be posted on the DSM-5 website on 20 January 2010.

The revision of the current version of the WHO’s International Statistical Classification of Diseases, ICD-10, and the development of the structure for ICD-11 is anticipated to be completed by 2014.

The Alpha Draft for ICD-11 is timelined for May 2010.

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