30 August 2010

Not just XMRV anymore.

In October, 2009, a paper by Lombardi, V., et al., ‘Detection of an Infectious Retrovirus, XMRV, in Blood Cells of Patients with Chronic Fatigue Syndrome’ was published in a leading   research journal, ‘Science’. This paper demonstrated evidence that a Murine Leukemia Virus (MLV) species, XMRV, was associated with ME/CFS in some (yet to be determined) manner, with the results showing the virus was present in 95% of CFS patient samples (Lombardi, V., et al., 2009).  This study also found that the XMRV virus was present in 4% of the healthy control samples (Lombardi, V., et al., 2009).

In January 2010, a paper by a group of UK scientists, from both the Faculty of Medicine of the Imperial College and Department of Psychological Medicine, Institute of Psychiatry, Kings College, published findings that failed to identify any association between XMRV and ME/CFS (Earlwin, et al,. 2010). This paper, Failure to Detect the Novel Retrovirus XMRV in Chronic Fatigue Syndrome, was published in the Public Library of Science, is discussed briefly in the blog entry dated 07 January 2010. 

In February 2010, another study came out of the UK, which again failed to find an association between XMRV and ME/CFS.  The findings of the Groom, H., et al (2010) paper, Absence of xenotropic murine leukemia virus-related virus in UK patients with chronic fatigue syndrome, were published in the journal Retrovirology.  The results of this paper are discussed in the blog entries dated 20 February 2010 and 25 April, 2010.
In the Netherlands, Kupperfield, F., et al (2010), published ‘Prevalence of xenotropic murine leukemia virus-related virus in patients with chronic fatigue syndrome in the Netherlands: retrospective analysis of samples from an established cohort’ in the British Medical Journal.  Again, this study failed to identify XMRV in the CFS samples used in the research (Kupperfield, F., et al. 2010).

Increasingly, during the period of time since the publication of the Lombardi, V., et al., (2009) paper, patients, families, carers, medical professionals, researchers, have debated the possibilities for such conflicting results.  Judy Mikovits at the WPI, stated that XMRV was notoriously hard to find, stating that the virus is
'...in too low a copy number in the genomic DNA (that is the provirus..integrated into the cells DNA) ..there may be less than 10 copies of provirus in 10 million cells..so unless you amplify the 1 microgram of genomic DNA from uncultured cells you might miss it' (Johnson, C., 2010).

Further to this, press releases from the Whittemore Peterson Institute detailed differences in the way the experiments were carried out which demonstrated why these studies were not true replications of the Lombardi, V., et al., (2009) study.  The Whittemore Peterson Institute sent a letter specifically to Dr Myra McClure, of the Earlwin, O., et al (2010) paper, suggesting that differing techniques and equipment were being used, as well as ME/CFS sample cohorts defined by criteria different to that which the Whittemore Peterson Institute used.  A discussion of this is available in the blog entry posted 20 Feburary, 2010.

On the 22 of June, 2010, a press release was published which stated that a combined team of scientists from the Food and Drug Administration, (FDA) and the National Institutes of Health, (NIH), had completed a replication of the Lombardi, V., et al., (2009) study, which not only confirmed the original findings, but expanded on them. It was soon announced, however, that due to conflicting results with a paper published by the CDC, a halt was placed on the Lo, S., et al (2010) publication.  Again, debate about the studies was further fuelled by involved parties; researchers, patients, doctors, and support organisations.

At 7am, New Zealand time, on August 24, the press embargo was lifted, and the Lo, S., et al (2010) paper was finally available online.

Lo, S., et al (2010) used 37 whole-blood and serum samples which had been collected from individuals with ME/CFS in the mid 1990's.   Lo, S., et al (2010)  also obtained repeat blood samples from 12 of the initial 37 patients; 4 of which were collected two years after the first samples were taken, and the remaining 8 were collected again in 2010.  Alongside this, blood samples were collected from 44 healthy controls.  Lo, S., et al (2010) reported that they used nested PCR techniques to target the gag gene of any XMRV DNA sequences present, as well as other MLV-like DNA.

The results of the Lo, S., et al (2010) demonstrated that 32 of 37 (86.5%) samples from ME/CFS patients revealed positive amplification of MLV-like viral gene sequences in the nested PCR, compared with  3 of 44 (6.8%) volunteer blood donors.  On testing of the 8 repeat samples collected in 2010, 7 remained positive, although all 8 reportedly remain symptomatic. 

In reading the results and discussion of the Lo, S., et al (2010) paper, one thing becomes glaringly obvious.  The results fail to report any specific findings of XMRV, that mouse virus variation which many people have taken great pains to undertsand over the past several months.  Instead, Lo, S., et al (2010) reports finding MLV's, (Murine Leukemia Viruses), which are a genus of gamma retroviruses, of which, XMRV is a species.  In fact, Lo, S., et al (2010) identified 4 variations of MLV's, not all of them xenotropic (warranting the XMRV label).  Judy Mikovits reports presenting a paper at the Cold Spring Harbor RNA tumor virus meeting in May 2010 demonstrating samples in the Lombardi, V. et al (2009) paper had Xenotropic (as in XMRV) and polytropic MLV variants as well as at least one more variant.  (Ketei, M., 2010). Furthermore, in comparing the 8 samples collected in 2010 with samples collected from the same 8 individuals with ME/CFS 15 years ago, it was apparent that the MLV had gone through significant mutation (Lo, S., et al. 2010).  “That’s just what you’d expect from a retrovirus,” said Alter. “That’s more evidence that this is a real agent, not a sequence floating around in the lab.” (Ketei, M., 2010).

Aside from the different variations of MLV identified in the Lo, S., et al (2010) publication, is the startling evidence that almost 7% of the controls, all of whom are blood donors, tested positive for these MLV variants.  This is indicative that these variations of MLV's are likely in the public blood supply, at least in the USA, where the samples were taken.  Mindy Kitei, of CFS Central, reports that Harvey Alter is commencing studies to determine if the MLVs identified in the Lo, S., et al (2010) paper, are potentially transmitted by blood (Ketei, M., 2010).

It is important to state that at this stage, there is not sufficient evidence to suggest MLV's are causative or co-morbid pathologies to ME/CFS.

News of the publication of the long awaited Lo, S., et al (2010) paper spread quickly across the internet, with discussions, blog posts, news articles and opinions being printed and reprinted through social mediums such as facebook.  It appears, however, that in some areas of the world, namely the UK, the news has been much slower off the press. Andrea Pring, writer and fellow ME/CFS patient, reports on her blog, Dancing with the Sandman, some of the contextual factors possibly contributing to the lack of news coverage in the UK, including the involvement of Professor Simon Wessley in the advisory panel of the Science Media Centre (Pring, A., 2010).  For further detail on this, please read Andreas blog post titled 'The Truth Behind the Headlines (August 29, 2010).

I would now like to take this opportunity to print a public thank-you to all the researchers, medical professionals, advocates, organisations, carers, families and supporters who have worked tirelessly over the decades, in the search for explainations and answers to this illness. It is far from over; the exploration continues, but we can be graterful of the advance in knowledge of this disease that has been made in the past few months.

Specifically, I woould like to thank Annette and Andrea Whittemore; Annette, in her quest as a mother to give her daughter the opportunity of quality of life and improved health, has given hope of a greater quality of life and health to all sufferers of ME/CFS across the globe.  And Andrea, in advocating for her own health, as well as advocating for the work of the Whittemore Peterson Institute, has given a voice to all ME/CFS patients, worldwide.  For this, we thank you both.


"Detection of MLV-related virus gene sequences in blood of patients with Chronic Fatigue Syndrome and healthy controls,"

Erlwein, O., Kaye, S., McClure, M., Weber, J., Wills, G., Collier, D, Wessely, S., and Cleare, A., (2010). Failure to Detect the Novel Retrovirus XMRV in Chronic Fatigue Syndrome.  Retrieved 29 August 2010 from: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0008519.

Frank J M van Kuppeveld, Arjan S de Jong, Kjerstin H Lanke, Gerald W Verhaegh, Willem J G Melchers, Caroline M A Swanink, Gijs Bleijenberg, Mihai G Netea, Jochem M D Galama, & Jos W M van der Meer (2010). Prevalence of xenotropic murine leukaemia virus-related virus in patients with chronic fatigue syndrome in the Netherlands: retrospective analysis of samples from an established cohort British Medical Journal : 10.1136/bmj.c1018

Groom, H., Boucherit, v., Makinson, K., Randal, E., Baptista, S., Hagan, S., Gow, H., Mattes, F., Breuer, J., Kerr, J., Stoye, J., Bishop, K. (2010) Absence of xenotropic murine leukaemia virus-related virus in UK patients with chronic fatigue syndrome. Retrovirology 7:10. Retrieved August 2010 from http://www.retrovirology.com/content/pdf/1742-4690-7-10.pdf

Johnson, C., (2010).  A Different Kind of XMRV? Dr. Mikovits and Dr. Racaniello on XMRV. Retrieved August 2010 from http://www.forums.aboutmecfs.org/content.php?187-Dr-Mikovits-and-Dr-Racaniello-on-XMRV
Pring, A., (2010). Dancing with the Sandman: The Truth Behind the Headlines. Retrieved August 2010 from http://dancingwiththesandman.blogspot.com/2010/08/truth-behind-headlines.html

Switzer, W. M.; Jia, H.; Hohn, O.; Zheng, H.; Tang, S.; Shankar, A.; Bannert, N.; Simmons, G. et al. (2010). "Absence of evidence of Xenotropic Murine Leukemia Virus-related virus infection in persons with Chronic Fatigue Syndrome and healthy controls in the United States". Retrovirology 7 (1): 57. doi:10.1186/1742-4690-7-57. PMID 20594299.

27 August 2010

Alter Paper

I am unable to write the commentary on this that I am so desperate to post, however, here are some of the key links I've had a look at over the past few days.

I will return to this, as my health allows, and discuss it, as I've done previously. If only for my own and my families benefit.

Online version of the Alter, H., et al (2010) paper

WPI response to the Alter, H., (2010) paper

Judy Mikovits responds to the Alter, H., (2010) paper

Harvey Alter discusses the delay in publication of the NIH/FDA study

Mindy Keitel, via CFS Central, discusses the Alter, H., et al., (2010) paper

Pictorial demonstration of the MLV family, of which XMRV is only one genomic variation

I encourage people to contribute to this list, and to discuss their interpretations and what it means for them, for us and for the rest of the world. 

There are challenges already with getting the news out about this finding, and suggest that if you live in an area where you don't feel there is adequate coverage of these groundbreaking findings, inform your local news agencies, educate your government representatives, print off copies of the paper and take it to your GP.

As I stated, I would like the opportunity to discuss this paper, specifically the science, and hopefully in a few days, the opportunity will arise.  There are going to be all sorts of aspects to this scientific development, political, social, and historical.  Not being from the UK or USA, I don't feel well enough informed to address some of these adequately on my own, so I do welcome any contributions, particularly in the political and historical areas.

22 August 2010

The Grand Opening of the Whittemore Peterson Institute

'As wonderful as these facilities are, and they are truly wonderful, whats really important is whats gong to happen in these facilities, what the people in those facilities will do when they break down barriers; when they discover new things that will make the health care of the state the nation and the world better'.

- Dr Milton Glick, President of the University of Nevada

Grand Opening of the Whittemore Peterson Institute

20 August 2010

XMRV name change: the benefits and detriments.

There is a blog entry dated 29 December 2009, which addresses, very briefly, the names ME, CFS, Post Viral Fatigue, and so  forth.  it is beneficial for people to have a read of that entry, and it's attached links, as a background to this entry.  However, this entry discusses the proposed change from XMRV to HGRV, and HGRAD.

For the first time on this blog, apart from the blog entry about my personal story (dated 28 December, 2009), the  information discussed will be somewhat more subjective than usual, because of the nature of the discussion, and my own  interest and understanding of it.  What is presented here, therefore, are my own opinions, and must be interpreted as only  that.  People will not always agree with each others opinions and views, no more so mine than anyone elses, but I do ask that  people take time to read and understand the rationale behind such opinions, and use that to further develop their own ideas and values, whether in agreement or disagreement.

On 19 August 2010, a notice began circulating on ME/CFS websites and blogs from Rich Van Konynenburg, PhD, on behalf of Dr. Burrascano, MD, who attended the first official XMRV symposium of the Whittemore-Peterson Institute (Prohealth, 2010). The notice states firstly that a working group has been established to regularly meet and appraise the developments around what we are currently referring to as XMRV and it's association with ME/CFS.  The notice goes on to report that a new name has been proposed for XMRV and it's association with ME/CFS, and this announcement is expected to be made at the NIH retroviral conference this September Institute (Prohealth, 2010).  Reflecting on this, provides a good opportunity to reflect on the XMRV label, how it has been used, and  the benefits, detriments of changing this.

XMRV or Xenotrophic Murine virus-Related Virus, has been been used in ME/CFS circles since the news broke in October 2009 that a possible link had been identified between it and ME/CFS.  Before that, it had been identified in 2006 as potentially involved with both hereditary and spontaneous prostate cancer (Schlaberg R., et al. 2009). The name Xenotrophic Murine virus-Related Virus tells us that this virus that the WPI connected with ME/CFS in October 2009 is related to a retrovirus that originates from mice.  It does not cause disease in it's original hosts (the mice), but once it is transferred to another species, say humans, and inserted into their DNA genome, it can code for a provirus, which causes either active or latent infection (Belshaw, R., et al. 2004).  For further information on this replication process, have a look at the entry dated 28 December, 2009).

The new name proposed for what we are currently calling XMRV is Human Gamma Retrovirus (HGRV), and for the consequential symptoms and disease pathology, Human Gamma Retrovirus Associated Disease (HDRAD).  This would suggest that the signs and symptoms people experience as a result of the infection, would be referred to as HGRAD.  This would indicate, assuming that XMRV, or HGRV is causative to ME/CFS, that people who currently have a diagnosis of ME/CFS will therefore have a diagnosis of HGRAD, a disease process associated with the Human Gamma Retrovirus.

There are a number of thoughts and perspectives on this proposed change of name.  Of course,  it hasn't even been one year since the WPI announced their XMRV findings, people with ME/CFS are still getting used to the possible XMRV connection and label.  This disease already has a number of different names attached to it, and to have yet another name added to the list, is going to cause confusion.  Especially so because people have already started using the term XMRV for educational and promotional purposes.  Another reason is that this is yet another opportunity for the CDC and the Wessley subscribers to to continue to deny that ME/CFS is pathophysiological disease process, and promote their CBT and GET therapies.

However, and this next part is my own opinion, feel free to challenge it.  The label XMRV never differentiated between the infections that it had potentially been linked to; prostate cancer and ME/CFS.  It fails to acknowledge this retrovirus as the first gamma retrovirus known to infect humans, which is the genus that differentiates it from HIV.  In terms of a medically terminological label, HGRV, is a much more accurate informative and accurate label for the retrovirus known currently as XMRV.  Yes, the retrovirus is still related to xenotropic murine virus, but that isn't clinically relevant in the infection process, or treatment of prostate cancer or ME/CFS. 

HGRV highlights that this is a (the first) gamma retrovirus discovered that effects humans, and HGRAD allows the flexibility for it to be used to cover various disease processes caused by the retrovirus; namely prostate cancer and ME/CFS currently.  There will need to be work done in terms of education and promotion that ME/CFS is one and the same as HGRAD for those who test positive for the disease.  As we would for any new name given to the disease.  People must to continue to advocate for acknowledgment from those organizations who have mistreated and misrepresented people with this illness, and ensure that a change of name does not negate it's history of management.  In the meantime, we are still awaiting evidence of whether this retrovirus is causative of, or co-morbid to ME/CFS, evidence which hopefully will come out shortly in the form of a science paper published in the Journal of the Proceedings for the National Academy of Sciences.


Belshaw, R; Pereira V; Katzourakis A; Talbot G; Paces J; Burt A; Tristem M. (). "Long-term reinfection of the human genome by endogenous retroviruses". P Natl Acad Sci USA

Van Konynenburg, R.,  (2010). WPI Symposium News: Propose Name XMRV be Changed to HGRV. Retrieved on 20 August, 2010 from http://www.prohealth.com/library/showarticle.cfm?libid=15543&utm_source=SiteTracking&utm_medium=SiteTracking&utm_campaign=home_LatestNews


Prohealth notice from Rich Van Konynenburg