RiME: XMRV and MPs Referendum on ME Research

RiME:  XMRV and MPs Referendum on ME Research

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Campaigning for Research into ME (RiME)

XMRV and MPs Referendum on ME Research

In the wake of news on the XMRV virus [retrovirus], it might be an opportune time to write to those MPs who haven’t signed up to the MPs Referendum on ME Research. For more details and list of MPs who have signed see www.rime.me.uk

The article that was on the front and inside pages of the Independent is below. It should print off neatly on one page.

Below that is a letter that can be used as it is or as a guide.

Paul Davis rimexx@tiscali.co.uk

——————-

Front Page of  THE INDEPENDENT Friday 9 October 2009

Has Science found the cause of ME?

Breakthrough offers hope to millions of sufferers around the world

By Steve Connor Science Editor

SCIENTISTS SAY they may have made a breakthrough in understanding the cause of chronic fatigue syndrome – a debilitating condition affecting 250,000 people in Britain which for decades has defied a rational medical explanation.

MRC Research Workshop: Final Agenda

MRC Research Workshop: Final Agenda

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

As I was in contact with MRC Corporate Information and Policy, today, I requested confirmation of the presenter on “Fatigue” at today’s meeting which had been listed on the Agenda as “tbc”.

I have been advised that it was not possible to secure a speaker for the proposed session on Fatigue, but that an Open Session was added towards the end of the day. 

A final copy of the Agenda was provided for my information. I am advised that this will be published on the MRC website, early next week.

Note that this is the 3rd Agenda that has been issued (on 19 November) and it supercedes the two previous files posted on this site and elsewhere.

Final Agenda provided on 19 November in PDF format: Final Agenda MRC CFS ME Workshop 19- 20 November 2009

Prof Peter D White: Neurology and Psychiatry SpRs Teaching Weekend

Prof PD White: Neurology and Psychiatry SpRs Teaching Weekend

Shortlink for this posting: http://wp.me/p5foE-2p0

14 November 2009

THE BRITISH NEUROPSYCHIATRY ASSOCIATION

http://www.bnpa.org.uk

http://bnpa.org.uk/doc/HANDBOOK.pdf

Neurology and Psychiatry SpRs Teaching Weekend

12 to 14 December 2008 St Anne’s College – Oxford

THE ESSENTIALS OF NEUROPSYCHIATRY

Presentations:

[...]

09:50 Chronic fatigue syndrome: neurological, psychological or both?

Peter White, Professor of Psychological Medicine, Barts and the London Medical School

The extract I am appending is a summary of Professor Peter Denton White’s presentation (Page 46 of PDF) in which he talks about the taxonomy of CFS “being a mess”.

During his Royal Society of Medicine “CFS” Conference presentation, in April 2008, White had said, ominously:

“…So ICD-10 is not helpful and I would not suggest, as clinicians, you use ICD-10 criteria. They really need sorting out; and they will be in due course, God willing.”

See unofficial transcript of part of White’s RSM presentation, here, in which he presents his thoughts on current ICD taxonomy:

Prof Peter White discouraging RSM Conference from using ICD-10: http://tinyurl.com/PDW-RSM-ICD-10

In an April 2009 paper, co-authored by White, the authors propose a change to current ICD-10 codings:

http://www.ncbi.nlm.nih.gov/pubmed/19366500

Psychological Medicine Preprint “Risk markers for both chronic fatigue and irritable bowel syndromes: a prospective case-control study of primary care”

In the section “Implications for Further Research” the authors state that because the paper finds that:

“These data also suggest that fatigue syndromes are heterogeneous (Vollmer-Conna et al. 2006), and that CFS/ME and PVFS should be considered as separate conditions, with CFS/ME having more in common with IBS than PVFS does (Aggarwal et al. 2006). This requires revision of the ICD-10 taxonomy, which classifies PVFS with ME (WHO, 1992)”

 Presentation given at Neurology and Psychiatry SpRs Teaching Weekend

http://bnpa.org.uk/doc/HANDBOOK.pdf

[Extract]

Presentation:

Chronic fatigue syndrome: neurological, psychological or both?

Peter White, Professor of Psychological Medicine, Barts and the London Medical School

Epidemiology of fatigue and CFS

Fatigue is a common symptom in both the community and primary care. When asked, between 10 and 20 per cent of people in the community will report feeling abnormally tired at any one time.

At the same time, fatigue is continuously distributed within the community, with no point of rarity.

Therefore any cut-off is arbitrary and the prevalence will vary by how the question is asked, the symptom volunteered, and its context. Between 1.5 % and 6.5 % of European patients will consult their general practitioner with a primary complaint of fatigue every year, the incidence varying by age and population. Fatigue is more commonly reported and presented to general practitioners by women and the middle-aged, and is most closely associated with mood disorders and reported stress. It does not seem to vary by ethnicity in the UK, but there is an intriguing paradox in that it is reported more commonly by those in high income countries, yet is presented to medical care more often in low income countries.

Prolonged or chronic fatigue is significantly less common than the symptom of fatigue and it is only in the last 10 years that consensus has emerged about the existence of a chronic fatigue syndrome (CFS), also called myalgic encephalomyelitis (ME). CFS is now accepted as a valid diagnosis by medical authorities in the UK, in the United States of America, as well as internationally. About one third of patients presenting to their doctor with six months of fatigue will meet criteria for a chronic fatigue syndrome. The other two thirds have fatigue secondary to another condition, most commonly mood and primary sleep disorders. Its primary symptom is fatigue, both physical and mental, which particularly follows exertion. Other symptoms agreed in consensual guidelines include poor concentration and memory, sleep disturbance, headache, sore throat, tender lymph glands, muscle and joint pain.

There are several criterion based definitions of CFS. These definitions were derived by consensus and have not been supported by empirical studies, and continue to be refined. Their utility stems from providing reliable criteria for research studies, rather than clinical use. The prevalence of CFS is between 2.5 % and 0.4 % depending on the definition used and whether comorbid mood disorders are excluded (that is mood disorders that are not thought to be the primary diagnoses). It is most common in women, the middle-aged, and ethnic minorities (unlike fatigue) – at least in English speaking countries.

The diagnosis and classification of CFS

The clinical taxonomy for CFS is a mess. The ICD-10 classification defines CFS within both the neurology chapter and mental health chapters. Myalgic encephalomyelitis, the alternative name for CFS, is classified as a neurological disease (G93.3) (a.k.a. post-viral CFS), whereas neurasthenia (a.k.a. CFS not otherwise specified) is classified within mental health (F48).

[Ed: Note that White does not mention, here, that Chronic fatigue syndrome is listed in ICD-10: Volume 3, The Alphabetical Index* at G93.3, the same coding as for Benign myalgic encephalomyelitis, and for Postviral fatigue syndrome (ICD-10: Volume 1: The Tabular List).]

*ICD-10: Volume 3, The Alphabetical Index:
http://www.scribd.com/doc/7350978/ICD10-2006-Alphabetical-Index-Volume-3

[Back to PDW]

(Incidentally, this mess is not specific to CFS, since there are several conditions within the neurology chapter of ICD-10 that are also classified in the mental and behavioural disorders chapter. For instance, Alzheimer’s disease is classified within neurology, whereas dementia due to Alzheimer’s disease is classified under mental health. My personal view is that it is high time that all mental health disorders and neurological diseases affecting the brain were classified within the same chapter, simply called diseases/disorders of the brain and nervous system.)

[Ed: The WHO Department of Mental Health and Substance Abuse, which is overseeing the revision of Chapter V (Mental and Behavioural Disorders), is also managing the technical part of the revision of Chapter VI (Diseases of the Nervous System). According to Dr Geoffrey Reed, Senior Project Officer, WHO Department of Mental Health and Substance Abuse, Proposal forms for ICD Chapter V and Chapter VI are in preparation and expected to be released shortly.]

[Back to PDW]

There is also a current debate between “lumpers” and “splitters” about the nosology of “functional” somatic syndromes (symptom defined conditions), such as CFS, IBS and “fibromyalgia”. Some argue that the close associations between the syndromes (those with CFS are also more likely to have fibromyalgia and/or IBS) argues in favour of their being different manifestations of one over-arching functional somatic syndrome (the “lumpers”). Others argue that these syndromes are best understood by exploring their heterogeneity (the “splitters”). There is evidence to support both arguments, but two large and recent epidemiological studies suggest that chronic unexplained fatigue, for one, is both associated with and separate from other “functional” somatic syndromes. In particular, predisposing risk factors are shared whereas triggering factors are different.

CFS is not an easy diagnosis to make, since misdiagnosis is common in patients diagnosed as having CFS. A recent audit of my CFS clinic revealed that 4 out of 10 new patients (n = 250) assessed did not have CFS, and that was after a third of referrals had already been rejected as not being CFS.

The most common misdiagnoses were mood disorders, especially depressive disorders, and primary sleep disorders, particularly sleep apnoea. Other misdiagnoses included coeliac disease and autoimmune conditions. Alternative neurological diagnoses were made in 2%.

Aetiology and pathophysiology

The aetiology of CFS is unknown, but there is evidence that different risk markers are associated with predisposition, triggering, and maintenance of the illness. Predisposing risk markers include female sex, middle age, mood disorders (especially depressive disorders), other symptom defined syndromes, such as irritable bowel syndrome, and possibly either sedentary behaviour or excessive activity. As might be expected CFS patients are more likely to have attended their GP, than healthy matched controls, even up to 15 years before onset, but recent work shows that those with IBS (and no CFS) have the same tendency.

Triggering risk markers are less well established, but there is sufficient evidence to support certain infections as aetiological factors not only for fatigue but also CFS, with the best replicated evidence supporting a role for Epstein-Barr virus infection, which triggers CFS in 10% of those infected.

Maintaining or perpetuating risk markers are most important in determining treatment programmes, since reversing maintaining factors should lead to improvement. Reasonably well established factors include mood disorders, such as dysthymia, illness beliefs such as believing the whole condition is physical, pervasive inactivity, avoidant coping, membership of a patient support group, and being in receipt of or dispute about financial benefits.

Few pathophysiological findings in CFS have been replicated in independent studies. Those that have been include down-regulated hypothalamic pituitary-adrenal axis, physical deconditioning, and discrepant reports between perception of symptoms and disability and their objective tests.

The latter finding is now supported by functional brain scanning studies suggesting altered brain activity with specific tasks. The discrepancy between subjective states and objective tests has been found before in other symptom defined syndromes, such as “fibromyalgia”, and may be related to enhanced interoception (the perception of visceral phenomena), a concept first described by Charles Sherrington in 1904. One hypothesis currently being tested is that the common predisposition to “functional” somatic syndromes is caused by enhanced interoception.

Recent work suggests that these factors may be reversed by rehabilitation.

Prognosis

Without treatment the prognosis of CFS is poor with a systematic review of outcomes finding the median full recovery rate was 5 % (range 0-31%) and the median proportion of patients who improved of 39.5% (range 8-63%). Being younger, having less fatigue baseline, a sense of control over symptoms and not attributing illness to a physical cause were all associated with a better outcome. The prognosis is considerably better after treatment.

Treatment

The NICE guidelines, published in 2007, were based on an updated systematic review. The essence of specialist care is rehabilitation, provided on an individual basis with an appropriately qualified and trained therapist. The two approaches with the greatest evidence of efficacy are cognitive behaviour therapy (CBT) and graded exercise therapy (GET). Approximately 60% of patients report significant improvement with these approaches and about 25%report full recovery, which lasts. No pharmacological treatments are recommended (antidepressants are ineffective), but symptomatic pharmacotherapy for specific symptoms (such as pain) or comorbid conditions such as depressive illness) can be helpful complementary treatments.

These rehabilitation approaches have not received universal approval from patient charities, with concerns that patients may be harmed by exercise therapies or that CBT implying that the condition is psychological.

Is CFS neurological or psychological?

This is a nonsensical question when one considers the neuroscience of consciousness and recent advances in functional brain physiology. The philosopher, John Searle, stated the answer to this Cartesian dualism that still bedevils western medicine. “Conscious states are caused by neurophysiological mechanisms, and are realised in neurophysiological systems.” Therefore it is not possible to have a psychological process or event without a neurological mediating process. It is neither of the mind or body; it is both.

Fatigue secondary to neurological diseases

Fatigue is commonly associated with chronic medical disorders, but it should be differentiated from fatiguability. Fatiguability is the onset of a physical sensation of fatigue and weakness after exertion and is commonly reported with neurological diseases such as multiple sclerosis and myopathies.

Apart from measures of disease activity, other associations of secondary fatigue in general that have been repeatedly found include sleep disturbance, mood disorders, inactivity and physical deconditioning. Studies of fatigue associated with multiple sclerosis are instructive and exemplary. As in all studies of secondary fatigue, measures of the severity or pathophysiology of the disease itself are associated with fatigue. Some cytokines are associated, but others are not.

Associations vary depending on the fatigue measure, confirming the multidimensional nature of fatigue, but all measures are associated with depression. Objectively confirmed sleep disturbance is also associated with fatigue. Fatigue associated with MS therefore requires biopsychosocial management.

There have been a number of studies of various treatments aimed at reversing the associations of secondary fatigue in general, in the hope they would help fatigue directly, with variable results. As with CFS, the most consistent evidence of efficacy has been with graded exercise programmes and CBT.

Attarian HP, Brown KM, Duntley SP, et al. The relationship of sleep disturbances and fatigue in multiple sclerosis. Arch. Neurol. 61 (2004), 525-8.

Baker R, Shaw EJ. Diagnosis and management of chronic fatigue syndrome or myalgic encephalomyelitis (or encephalopathy): summary of NICE guidance. BMJ 2007 doi: 10.1136/bmj.39302.509005. AE

Chambers D, Bagnall A-M, Hempel S, Forbes C. Interventions for the treatment, management and rehabilitation of patients with chronic fatigue syndrome/myalgic encephalomyelitis: an updated systematic review. J R Soc Med 2006;99:506-20.

Cleare AJ. The neuroendocrinology of chronic fatigue syndrome. Endocr. Rev. 24 (2003), 236-52.

Flachenecker P, Bihler I, Weber F, et al., Cytokine mRNA expression in patients with multiple sclerosis and fatigue. Mult. Scler. 10 (2004), 165-9.

Fulcher KY, White PD. Strength and physiological response to exercise in patients with the chronic fatigue syndrome. J. Neurol. Neurosurg. Psychiatry 69 (2000), 302-7.

Joyce J, Hotopf M, Wessely S. The prognosis of chronic fatigue and chronic fatigue syndrome: a systematic review. Q. J. Med. 90 (1997), 223-33.

Kroencke DC, Lynch SG, Denney DR. Fatigue in multiple sclerosis: relationship to depression, disability, and disease pattern. Mult. Scler. 6 (2000), 131-6.

Lyall M, Peakman M, Wessely S. A systematic review and critical evaluation of the immunology of chronic fatigue syndrome. J. Psychosom. Res. 55 2003), 79-90.

National Institute for Health and Clinical Excellence. Clinical guideline CG53. Chronic fatigue syndrome/myalgic encephalomyelitis (or encephalopathy): diagnosis and management. London, NICE, 2007. http://guidance.nice.org.uk/CG53.

Reeves WC et al. Identification of ambiguities in the 1994 chronic fatigue syndrome research case definition and recommendations for resolution.BMC Health Serv Res 3 (2003), 25.

Romani A, Bergamaschi R, Candeloro E, et al., Fatigue inmultiple sclerosis: multidimensional assessment and response to symptomatic treatment. Mult. Scler. 10 (2004), 462-8.

M. C. Tartaglia, S. Narayanan, S. J. Francis, et al., The relationship between diffuse axonal damage and fatigue in multiple sclerosis. Arch. Neurol. 61 (2004), 201-7.

Wessely SC, Hotopf M, Sharpe M. Chronic Fatigue and its Syndromes (Oxford: Oxford University Press, 1998).

Wessely S, Nimnuan C, Sharpe M. Functional somatic syndromes: one or many? Lancet 354 (1999), 936-9.

Wessely S, White PD. In debate: there is only one functional somatic syndrome. Br. J. Psychiatry 185 (2004), 95-6.

White PD, Thomas JM, Kangro HO, et al., Predictions and associations of fatigue syndromes and mood disorders that occur after infectious mononucleosis. Lancet 358 (2001), 1946-54.

White PD, Sharpe MC, Chalder T, DeCesare JC, Walwyn R; on behalf of the PACE trial group. Protocol for the PACE trial: a randomised controlled trial of adaptive pacing, cognitive behaviour therapy, and graded exercise, as supplements to standardised specialist medical care versus standardised specialist medical care alone for patients with the chronic fatigue syndrome/myalgic encephalomyelitis or encephalopathy. BMC Neurol 2007;7:6.

[ Extract ends, doc: http://bnpa.org.uk/doc/HANDBOOK.pdf ]

For detailed information on the proposed structure of ICD-11, the Content Model and operation of iCAT, the collaborative authoring platform through which the WHO will be revising ICD-10, please scrutinise key documents on the ICD-11 Revision Google site:
https://sites.google.com/site/icd11revision/
https://sites.google.com/site/icd11revision/home/documents

For information around the DSM and ICD revision processes see DSM-V and ICD-11 Directory page: http://meagenda.wordpress.com/dsm-v-directory/

Suzy Chapman
http://meagenda.wordpress.com
http://twitter.com/MEagenda

More evidence of inflammation in (ME)CFS: M Williams 14 November 2009

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

Update: I am advised that the PDF referenced in the text of Ms Williams’ article, below, is no longer available at the URL given. A cached html version of the document has been archived here:

http://www.meactionuk.org.uk/Infectious-mononucleosis-as-a-model-for-chronic-fatigue-syndromes.htm

Permission to Repost

http://www.meactionuk.org.uk/More-evidence-of-inflammation-in-(ME)CFS.htm

http://www.meactionuk.org.uk/More-evidence-of-inflammation-in-(ME)CFS.pdf

More evidence of inflammation in (ME)CFS

Margaret Williams

14 November 2009

In his presentation in Bergen on 20th November 2009, Professor Peter White’s power point slides state about (ME)CFS that maintaining factors include illness beliefs, the search for legitimacy, being on benefits, and the diagnostic label, and that immune or viral measures are NOT involved in the maintenance of the disorder

( http://www.unifobhelse.no/upload/Bergen%20What%20is%20CFS%202009.pdf )

White’s assertion that immune or viral measures are not involved in the maintenance of the disorder would seem to be a direct denial of the evidence of two of the world’s leading immunologists who specialise in ME/CFS, Professors Mary Ann Fletcher and Nancy Klimas, who recently published yet more confirmatory evidence of immune dysfunction in the maintenance of the disorder (Journal of Translational Medicine 2009:7:96: doi:10.1186/1479-5876-7-96). Their peer reviewed article was published immediately upon acceptance.

Fletcher and Klimas et al are clear that cytokine abnormalities are common in (ME)CFS and that the cytokine changes observed are more likely to be indicative of immune activation and inflammation, rather than specific for (ME)CFS, as people with fibromyalgia, Gulf War Illness, rheumatological disorders and multiple sclerosis may also have similar cytokine patterns.

The authors do, however, demonstrate that several of the abnormal cytokines show promise as potential biomarkers for (ME)CFS.

As Fletcher and Klimas et al point out:

“CFS studies from our laboratory and others have described cytokine abnormalities. Other studies reported no difference between (ME)CFS and controls. However, methodologies varied widely and few studies measured more than 4 or 5 cytokines. Multiplex technology permits the determination of cytokines for a large panel of cytokines simultaneously with high sensitivity.

“In this study, 10 of 16 cytokines examined showed good to fair promise as biomarkers. However, the cytokine changes observed are likely to be more indicative of immune activation and inflammation…Many of the symptoms are inflammatory in nature.

“There is a considerable literature describing immune dysfunction in (ME)CFS.

“The goal of this study was to determine if, using new technology, plasma cytokines had sufficient sensitivity and specificity to distinguish (ME)CFS cases from age-matched healthy controls….Amounts of cytokines in plasma or serum are often below the level of detection in traditional ELISA assays.

“The availability of sensitive multiplex technology permitted the determination of 16 cytokines simultaneously…In the (ME)CFS cases, we found an unusual pattern of the cytokines that define the CD4 T cell.

“Pro-inflammatory cytokines: A significant elevation in the relative amounts of 4 of 5 pro-inflammatory cytokines in peripheral blood plasma of patients with (ME)CFS was found when compared with the controls. In cases, lymphotoxin (LT)a was elevated by 257% and IL-6 by 100% over the controls.

“TH2 cytokines: Both interleukin (IL)-4 and IL-5 were elevated in (ME)CFS, with the median of IL-4 (being) 240% and of IL-5 (being) 95% higher in cases than controls.

“Anti-inflammatory cytokines: IL-3 was significantly lower in (ME)CFS patients.

“TH1 cytokines: IL-12 was significantly elevated (120%) and IL-15 decreased (15%) in cases compared to controls.

“IL-8 (CXCL8): this chemokine was 42% lower in the (ME)CFS patients.

“Along with the TH1 abnormalities, we found up-regulation of TH2 associated cytokines, IL-4 and IL-5, in the (ME)CFS subjects. Allergy is common in (ME)CFS cases. Years ago, Straus et al reported >50% atopy in 24 CFS patients.

“The probability of chronic inflammation in (ME)CFS patients is supported by the elevation of four members of the pro-inflammatory cytokine cascade , LTa, IL-1a, IL-1b and IL-6, in the (ME)CFS samples compared to controls.

“Interleukin-13, associated with inhibitory effects on inflammatory cytokine production, was lower in cases compared to controls.

“The inflammatory mediator IL-8 (a chemokine known as CXCL8) known to be responsible for migration and activation of neutrophils and NK cells was decreased in plasma of (ME)CFS patients.

“The observations of abnormal cytokine patterns in (ME)CFS patients support the reports of retrovirus infections.

“Recently, DNA from a human gammaretrovirus, xenotropic murine leukaemia virus-related virus (XMRV) was found in the PBMC of 68 of 101 patients compared to 8 of 218 healthy controls. Patient–derived, activated PBMC produced infectious XMRV in vitro. Both cell associated and cell-free transmission of the virus to uninfected primary lymphocytes and indicator cell lines was possible.

“The decreased natural killer (NK) cell cytotoxic and lymphoproliferative activities and increased allergic and autoimmune manifestations in (ME)CFS would be compatible with the hypothesis that the immune system of affected individuals is biased towards a T-helper (TH) 2 type, or humoral immunity-orientated cytokine pattern.

“The elevations in LTa, IL-1a, IL1b and IL-6 indicate inflammation, likely to be accompanied by autoantibody production, inappropriate fatigue, myalgia and arthralgia, as well as changes in mood and sleep patterns.

“This study is among the first in the (ME)CFS literature to report the plasma profiles of a reasonably large panel of cytokines assessed simultaneously by multiplex technique.

“Cytokine abnormalities appear to be common in (ME)CFS. The changes from the normal position indicate immune activation and inflammation.

“The results imply a disorganised regulatory pattern of TH1 function, critical to antiviral defence.

“The results from this study support a TH2 shift, pro-inflammatory cytokine up-regulation and down-regulation of important mediators of cytotoxic cell function”.

Since it is now unequivocal that people with (ME)CFS show markers of inflammation, what will be the impact on the Wessely School’s MRC PACE Trial that is predicated on the assumptions of deconditioning, on the “perception” of effort and on aberrant illness beliefs and whose participants are instructed about “sleep hygiene”?

XMRV Retrovirus: Round up 23: WPI NYT article, Coffin on NPR Radio, papers

XMRV Retrovirus: Round up 23: WPI NYT article, Coffin on NPR Radio, papers and Hillary Johnson on CFSAC

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

 

Media

New York Times  |  Denise Grady  |  11 November 2009

http://www.nytimes.com/2009/11/12/giving/12SICK.html

A Big Splash From an Upstart Medical Center

[A version of this article appeared in print on November 12, 2009, on page F8 of the New York edition.]

Related article: Is a Virus the Cause of Fatigue Syndrome? (October 13, 2009)

TO many people who suffer from the poorly understood illness called chronic fatigue syndrome, a recent study linking the disorder to a virus was a victory for the little guys.

For one thing, the study pointed to a physical cause for an illness that the medical establishment had often snidely dismissed as psychosomatic. The research could not be ignored: it was published last month in Science, one of the world’s pickiest and most prestigious journals…

Read full article here

—————-

NPR Radio  |  16 October 2009

Interview with Dr John Coffin (c0-author of Science Perspectives article)

http://www.npr.org/templates/story/story.php?storyId=113870280

10 mins 30 secs

Virus Tied To Chronic Fatigue Syndrome

Scientists have identified a virus lurking in 68 of 101 patients diagnosed with chronic fatigue syndrome. Whether the virus — known as XMRV — causes the syndrome is unclear. Molecular biologist John Coffin describes how the findings fit with what scientists know about XMRV.

Transcript also available

Scroll down NPR page for

Virus Linked To Chronic Fatigue Syndrome
by Jon Hamilton

8 October 2009

—————-

Papers

AHC Media LLC

http://ahcpub.com/hot_topics/?htid=1&httid=2005

Chronic Fatigue Syndrome — Could a “Stealth Virus” Be Lurking?

From Infectious Disease Alert | November 2009

Abstract & Commentary

By John F. Joseph, MD, FACP, FIDSA, FSHEA, Associate Chief of Staff for Education, Ralph H. Johnson Veterans Administration Medical Center; Professor of Medicine, Medical University of South Carolina, Charleston, is Associate Editor for Infectious Disease Alert.

Dr. John is a consultant for Cubist, Genzyme, and bioMerieux, and is on the speaker’s bureau for Cubist, GSK, Merck, Bayer, and Wyeth.

Source: Lombardi VC et al. Science. 8 October 2009 (10.1126/science.1179052).

Full Abstract and Commentary here

—————-

http://www.ncbi.nlm.nih.gov/pubmed/19906923?dopt=Abstract

J Virol. 2009 Nov 11. [Epub ahead of print]
Androgen Stimulates Transcription and Replication of XMRV (Xenotropic Murine Leukemia Virus-Related Virus).

Dong B, Silverman RH.

Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195.

XMRV is a gammaretrovirus originally identified in a subset of prostate cancer patients. Because androgens stimulate prostate tumors and some retroviruses, we investigated effects of dihydrotestosterone (DHT) on XMRV transcription and replication. Transcription from the XMRV U3 region was stimulated up to 2-fold by DHT, but only in cells containing a functional androgen receptor. Mutations in the glucocorticoid response element (GRE) of XMRV impaired basal transcription and androgen responsiveness. Furthermore, DHT stimulated XMRV replication by 3-fold, whereas androgen inhibitors (casodex and flutamide) suppressed viral growth up to 3-fold. Findings suggest that integration of the XMRV LTR into host DNA could impart androgen stimulation on cellular genes.

PMID: 19906923 [PubMed - as supplied by publisher]

—————-

Press Releases

Hemispherx

Source: Globe Newswire
Date: 11 November 2009
http://www.reuters.com/article/pressRelease/idUS198174+11-Nov-2009+GNW20091111 

Law offices Bernard M. Gross, P.C. filed a class action lawsuit against Hemispherx Biopharma, Inc.

Source: Marketwire
Date: 12 November 2009
http://finance.yahoo.com/news/INVESTOR-ALERT-Former-iw-3847944880.html

Investor Alert: Former Attorney General of Louisiana Charles C. Foti, Jr. and KSF notify Hemispherx Biopharma, Inc. investors of Lead Plaintiff Application Deadline in Securities Class Action Lawsuit

Source: MarketWire
Date: 12 November 2009
http://finance.yahoo.com/news/CORRECTION-Holzer-Holzer-iw-766428846.html 

Holzer Holzer & Fistel, LLC announces that it has filed a class action lawsuit on behalf of investors in Hemispherx Biopharma, Inc.

Source: MarketWire
Date:  12 November 2009
http://finance.yahoo.com/news/Izard-Nobel-LLP-Announces-iw-68919281.html

Izard Nobel LLP announces class action lawsuit against Hemispherx Biopharma, Inc.

—————-

Bloggers

Hillary Johnson  |  13 November 2009

New blog post about the recent CFSAC meeting in Washington, D.C. and the new scientific terrain created by the discovery of XMRV

THE FOG OF WAR

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

—————-

Commentary and quality forums

Rich Van Konynenburg via Co-Cure
12 November 2009

XMRV: necessary but not sufficient?

http://listserv.nodak.edu/cgi-bin/wa.exe?A2=ind0911b&L=co-cure&T=0&F=&S=&P=2951

—————-

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 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/

Medically Unexplained Psychologising of ME (MUPs) by Peter Kemp

An essay by Peter Kemp orginally published on Co-Cure

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

 

Medically Unexplained Psychologising of ME (MUPs)

Permission to repost

10 October 2009

In this essay I will explore some psychic phenomena that might be relevant to psychologising of illness.

Generalisations cannot practically be made, MUPs is not just heterogeneous from a psychic viewpoint – it is likely to be individual. So I can only explore my impressions and I hope you will read my theories as falling somewhere between the Origin of Speciousness and A Tale of Two Settees.

Use of some terminology has been unavoidable but I include a few definitions and illustrations as ‘Asides’ that I hope will help make the essay accessible to PWME.

Peter Kemp

Acronyms:

PWME = Person (or People) With ME

MUPs = Medically Unexplained Psychologising of ME

 

Medically Unexplained Psychologising of ME (MUPs)

Aside 1

AN ILLUSTRATION OF ‘PROJECTION’

Jack thinks that it would be very bad to be envious; this might be something his parents taught him. He notices envy in other people and condemns them for being envious. The envy that he so often notices might be real or not, it does not matter because it is HIS envy he is seeing. He is Projecting his envy onto other people to try and hide and control it within himself.

WITHDRAWAL OF PROJECTION

Projection is an unconscious process, people are not aware when they are doing it, but if they can become aware of the true source of a problem there may be an opportunity for growth.

One day Jack says to Jill, ‘I think you are envious of Mary’s little lamb’; and Jill says, ‘actually, I love Mary so much I gave her that lamb. I think you are envious because I get on so well with Mary.’ Jack’s theories fall apart and his projection is laid bare. If he is honest and humble enough he can then discover his own envy and stop projecting it. It may help if Jill points out ‘what’s wrong with being envious anyhow? It is part of how I know what I like and what I want’.

Through this uncomfortable experience Jack stops projecting envy and finds that natural feelings of envy can help him to make decisions about what he wants in life.

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Projected Fear

PWME represent ‘ideal’ subjects for the projection of all sorts of fears, Fear of losing control, Fear of weakness, Fear of illness, Fear of physical inadequacy, and perhaps worst of all, Fear of fear. For some MUPs I suspect that subtler projections and issues arise, such as Fear of being wrong and Fear of being misunderstood. All these fears have their roots in the psyche and are most troublesome when their origins are unconscious and when strongly denied. This may result in odd behaviour that may nevertheless be easily justified, but the justifications do not reveal the true motives behind the behaviour, instead they contribute to their concealment.

To confront fear it must be acknowledged but if it originates from an intense inner conflict it might be that the ego is not ready to withstand it. In these circumstances an internal struggle is maintained to repress some aspects of a complex in order to protect the ego. Enacting these conflicts in the world is a common way of reinforcing defences and avoids addressing the conflict directly. Unfortunately, this never resolves the issue at its source and means that substitute conflicts must constantly be found. As such projecting Fear may be predisposing and initiating; and because projection is an avoidance strategy, it is likely to be a maintaining factor in MUPs.

Withdrawal of Projection

For some people in whom contact with PWME arouses issues with fear, the psyche may seize this as an opportunity for growth. If someone projects fear onto another they may sometimes be able to compare their projection with the actual person. If discrepancies are found then the projection might start to weaken, then the projector has an opportunity to challenge and eventually withdraw the projection.

For example; a person fearful of losing control might project this onto a PWME; if they then realize that the PWME is actually coping well (with what for many people is a terrifying aspect of disability), the projector may think something like; ‘I thought he was weak, but I could not cope so well with such a loss of control’. This represents a stage of withdrawal of a projection as the projector has discovered that the source of the fear is within himself. Such situations might be considered MUPs based on transient / opportunistic factors; and is I suspect, a very common occurrence. Some MUPs might be able to relate to this if they find they vacillate between impatience and respect towards a PWME. This could be a sign that projections are weakening and the source of fear might be discoverable.

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

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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/

ME in Parliament: Written answers 5 November 2009

ME in Parliament: Written answers 5 November 2009

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

The ME Association reports:

http://www.meassociation.org.uk/content/view/1069/70/

Questions in Parliament: notifiable illness in schools and funding for biomedical research

Parliamentary questions about making ME/CFS a notifiable illness in schools and the level of Government funding for biomedical research into illness in the 2008-9 financial year were answered in the form of written replies yesterday (5 November 2009).

NOTIFIABLE ILLNESS IN SCHOOLS

Paul Rowen (Lib Dem, Rochdale) asked the Secretary of State for Health whether his department had any plans to make ME a notifiable illness in schools and what recent discussions his department has had with officials from ME charities and campaign groups to make ME a notifiable illness in schools.

In a written answer, Anne Keen, Parliamentary Under Secretary of State for Health, replied:

“We have no plans to make chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) a notifiable illness in schools.

“Since 2007, the Department has received a large number of requests from many organisations, including CFS/ME stakeholders, campaigning for their disease or condition to be recognised as a notifiable disease. The Department’s position remains that this classification should be used only for a relatively small number of infectious diseases where monitoring is required to identify sources of infection, and not as a means for collecting statistical information on the prevalence of specific conditions.”

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FUNDS FOR BIOMEDICAL RESEARCH

In a second written question, Mr Rowen asked the Health Secretary what funds his Department allocated for biomedical research on the causes and treatment of ME in the 2008-09 financial year.

Gillian Merron, Minister of State for Public Health replied:

“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.

“The MRC’s total expenditure on chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) research amounted to £730,000 in 2008-09.

“Over the 10 years to 2008-09, a large part of the Department’s total expenditure on health research was devolved to and managed by national health service organisations. Details of individual NHS supported research projects undertaken during that time, including a number concerned with CFS/ME, are available on the archived national research register.

https://portal.nihr.ac.uk/Pages/NRRArchiveSearch.aspx

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The weblink given out in Parliament does not appear to be working this afternoon, but the £730,000 relates to the award of a National Institute of Health Research Clinician Scientist Fellowship to Dr Esther Crawley, Senior Clinical Lecturer at the Centre for Child and Adolescent Health at the University of Bristol.

Click here to read the Bristol University press release, dated 27 February 2009.

http://www.bristol.ac.uk/news/2009/6217.html

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