Bringing the Heat: An ME/CFS Blog

Bringing the Heat: An ME/CFS Blog

A wide-ranging, often rankly speculative and occasionally irreverent take on the world of chronic fatigue syndrome (ME/CFS)

2011 – the Year Ahead for ME/CFS

http://blog.aboutmecfs.org/?p=2059

by Cort on January 10, 2011

Is 2011 going to be a big year? Yes it is! Some big issues are being decided.
XMRV – XMRV has taken a longer than anyone expected but expect some real answers this year with important studies finishing up.
* BWG – hopefully news in 6 months
* Lipkin – may take up to a year
* Lo/Alter – isolating virus, integration in human genome (?)
* Glaxo Smith Kline/CAA study – due sometime this year
* Joliceur – studying XMRV positive patients
* Dr. Mikovits XMRV immune signature paper to be published
* Miller – pilot study under way soon?
* Montoya/Lipkin comprehensive pathogen search
* Singh – autopsy and CFS XMRV study sometime this year
State of the Knowledge Conference on CFSNIH – The State of the Knowledge Workshop in April will highlight what the biggest medical research funder in the world, the NIH, deems is worthy to research in CFS and should form the basis for a major grant opportunity for CFS – the first in about 6 years. Funding for CFS at the NIH, accounting for inflation, is significantly lower than its been in at least 15 years. Ten years ago we had three federally funded CFS Research Centers, one of which was run by Dr. Klimas.
Dennis Mangan has brought new energy and vitality to the program. CFS is now ME/CFS. A new website will soon be up. He has enlarged the CFS Working Group and is bringing patients into the process. Is the year the NIH gets serious about ME/CFS?
CDC- The new director at the CDC, Dr. Unger, will start put her imprint on a CFS research program that is inefficient, out of favor in the research community and unimpressive. Dr. Reeves was relieved for a reason – why we don’t know, but we can assume that Dr. Unger does – and changes should occur in that area, at least. Funding for the CDC program has fallen sharply as well. Five years ago the CDC was funding the Dubbo projects and inviting Dr. Klimas, the CAMDA Conference and data mining experts others to come in to play with their Pharmacogenomics dataset – now it can barely muster a presence at the IACFS/ME Conference. Will Dr. Unger follow Dr. Mangan’s lead and reach out to the ME/CFS research community? There’s no sign of that yet but it’s still early.
Several International Conferences should be produced by the CDC, including one on the all important question of how to define this disorder. That could be an exciting conference as the proponents of a Canadian Consensus type definition go head to head with the proponents (CDC) of an Empirical-type Definition.
Non-Profits and Others – The Whittemore-Peterson Institute will open its door to patients providing a much needed new resource for innovative treatments. The CFIDS Association will expand its Biobank and keep building its Research Network. After being out of the news for several years, Stanford will definitely pop into the news as Dr. Montoya publishes several papers on infection and CFS and builds support for a Chronic Infectious Illness Center at Stanford.
Across the pond the PACE trial will reportedly be published soon – an important study for UK residents and really everyone with CFS.
This is a year of change and hopefully a year of recovery for a research field that has attracted little funding or interest over the years. With the budget deficit problems in the US increasing funding won’t be easy but relatively small amounts could go a long way in a disorder as underfunded as ME/CFS is.
Notable Events
* Whittemore Peterson Institute Starts Treating Patients
* HHV-6 Conference – Feb.
* State of the Knowledge Workshop – April
* Invest in ME Conference – May
* CAA \NIH Three Day Banbury Conferences of CFS Researchers (summer?)
* Ottawa IACFS/ME International Conference in Sept
Stanford - Dr. Montoya collaborates with Ian Lipkin on comprehensive pathogen study in CFS. Attempts to correlate MRI findings with infection may be successful and he may have found a biomarker associated with cancer (!) in infected patients. He will hold a ‘major research meeting’, open a new website and publish three papers on antiviral trials in CFS. This the year the Montoya effort on Stanford hopefully really takes off.
WPI is working in conjunction with NCI researchers to produce better diagnostic tests on XMRV. We know they have many isolates that need sequencing. They are extending XMRV testing into other groups. The family incidence studies will be fascinating. The cancer study reported at the Reno Conference hasn’t been published yet.
Regarding other studies the WPI does not list dates but have a number of interesting immune studies underway. They list seven studies; on cytokines/chemokines, HHV-6 (latency, assay development), genetic susceptibility to infection, interferon/RNase L pathway and immune activation/dysregulation caused by herpesviruses.
CFIDS Association of America research- CAA does not list dates but some studies have published results and others are continuing. Some may finish up this year. They list six studies underway including HPA axis dysfunction, acid and ion based receptors upregulation on blood cells, impaired blood flows to the brain and the effects of nitric oxide and oxidative stress on problems standing, a knowledge base of CFS produces new theories, gut microbiome alterations during exercise cause post-exertional malaise, increased blood lactate in brain suggestive of mitochondrial problems.
Hemispherx and Ampligen - Hemispherx was given another year to convince the FDA that they should give Ampligen, still the only drug focused almost entirely on CFS, their seal of approval.
NIH
NIH studies Ending this Year - a small palette from a big agency. There are some breakthrough studies here – just not a lot of them. POT’s, blood flows and sympathetic nervous system activation are ‘hot’ topics (if you can call a few studies a ‘hot’ topic). For me the Baraniuk brain proteome study is the biggie…CFS”>http://projectreporter.nih.gov/repor…TOKEN=49016940
* Baraniuk and the Brain (Apr 2011) – Baraniuk seeks to validate his last studies protein expression findings evidence of increased amyloid levels, oxidative stress, blood vessel injury in the spinal fluid of people with ME/CFS plus new findings. This study is reportedly done.
* Biaggioni and Blood Vessels (Aug 2011)- theorizes reduced nitric oxide production by the epipthelial cells lining the blood vessels result in sympathetic nervous system activation, disrupting blood pressure causing POTS and low blood volume. This occurs in concert with increased immune activation and oxidative stress
* Freeman and Nitric Oxide (unknown) – seeks to differentiate between POTS caused by nerve damage (high nitric oxide) and without nerve damage (low NO). They will alter NO and sympathetic nervous system activity levels and determine how doing that effects these two types of POTs patients.
* Friedberg and Fatigue (Dec 2011) – Fatigue Self-management in CFS – using lifestyle management techniques to reduce fatigue and improve quality of life
* Friedman and Viagra (June 2011) - Uses Viagra to increase blood flows to the brain (the big brain not the little one)to improve fatigue. Will use SPECT scans to assess blood flow.
* Jason and Risk Factors (June 2011) – did a community based survey to assess socio-environmental risk factors associated with CFS and chronic fatigue
* Spencer Shawn and HHV6 (Aug 2011) – HHV6 – determine if HHV6 infection proceeds by impairing proteins involved in cellular defenses. Determine if a treatment is effective in HHV6 infected cell lines.
CDC
* Two International Conferences? – One on the definition of CFS – both are a year overdue…
* Study of CFS and Chronic Unwellness in Georgia - somehow allostatic load and metabolic syndrome linger on…This sounds like another ‘fat’ study….This study will determine knowledge, attitudes, and beliefs concerning CFS and the effect on clinical course of the illness, evaluate direct and indirect economic impact of CFS and barriers to healthcare utilization. Evaluate association between medical history, exercise patterns, tobacco use, and CFS. Refine analysis of allostatic load, cortisol, alpha amylase, inflammation index, and genetics of CFS. Evaluate incidence of metabolic syndrome and diabetes.
* Mayo Clinic Rochester Epidemiology Project – Retrospective study will utilize medical records from the Rochester Epidemiology Project to study risk factors associated with the incidence of CFS in the population of Olmstead County; ie they will look at medical records dating backing to birth to see if people who later developed CFS had different medical patterns than people who did not.
* In-Hospital Clinical Study - This study will identify brain regions associated with cognitive deficits and neural circuits involved in CFS-associated interoception. Evaluate HPA axis, autonomic nervous system, immune system, and neuroendocrine system function during stress tests. Identify genetic and epigenetic covariables Identify pathophysiologic and clinical subsets presenting as the illness CFS.

Latest known news about XMRV (from ESME)

Summary of the Oslo XMRV-seminar, November 28th, 2010

Excerpts of the XMRV-conference in Oslo on 28/11/2010. Lecture by Dr. Judy Mikovits, Whittemore Peterson Institute and Lecturer of Dr. Mette Johnsgaard, Lillestrom Helseklinikk, Center for Treatment of Chronic Diseases

Excerpts of the XMRV-conference in Oslo on 28/11/2010
Lecture by Dr. Judy Mikovits, Whittemore Peterson Institute
Dr. Mikovits began by acknowledging several other famous researchers and telling about her collaborations with them, including several researchers at the National Cancer Institute, the Cleveland Clinic, the SAIC and, of course, the Whittemore Peterson Institute.
Dr. Mikovits proceeded by explaining how the novel retrovirus was found in prostate cancer patients in 2006 and 2007, and named XMRV Xenotropic Murine Leukemia virus-Related Virus. She showed how the infectious clone was constructed and sequenced and found to be a novel human gammaretrovirus. Dr. Mikovits then showed how ME/CFS patients have several inflammatory sequelae including antiviral enzyme dysfunction (RNase L), decreased NK cell number and function, increase in activated T cells and increases in inflammatory cytokines/chemokines. She believes that these dysfunctions might be explained by an ongoing retroviral infection and proposed that these patients could be infected with XMRV.
Dr. Mikovits went through some of the technical information on how they were able to detect XMRV proteins and positive antibodies leading up to the October 9^th , 2009 Science article. She also gave the audience a little insight into newer detection techniques that are currently being developed.
Dr. Mikovits showed possible reasons for the disparity in XMRV detection, including patient selection in heterogeneous diseases, variation in methods, possibility of scattered world-wide distribution (as in HTLV1), higher levels of sequence diversity, looking for retrovirus in blood, prostate cancer not being the in vivo reservoirs, and false positives due to PCR contamination with mouse cells.
She showed that infectious XMRV and antibodies were found in samples from UK ME/CFS patients and in Norwegian patients. The Norwegian study is ongoing and Dr. Mikovits is cooperating on it with Dr. Johnsgaard of the Lillestrøm Clinic. She then went on to explain the finding of 2 strains, XMRV and PMRV, and the probability that both can be present at the same time in the same patient.
Dr. Mikovits showed a slide that made it obvious that the virus has a simpler make-up than HIV and HTLV1. Interestingly, the LTR is stimulated by hormones, proving why the LNCaP cell line is the best choice. It might also be a possible clue to pathogenesis as hormones and inflammation might increase the replication of XMRV.
HTLV1, a complex deltaretrovirusis not present in Europe or the US, but does exist in many individuals in other countries and carries a 10% lifetime risk of developing cancer and inflammatory syndromes. XMRV is probably more similar to HTLV than to HIV. HTLV is asymptomatic in the majority of individuals.
Dr. Mikovits ended her talk by showing some cytokine/chemokine profiles found in adult T cell lymphoma/leukemia and comparing them to many of the same findings in patients with XMRV.
ESME in cooperation with Dr. Mette Johnsgaard – Medical Reporter of the ESME Think Tank 

http://esme-eu.com/esme/category28.html


Excerpts of the XMRV-conference in Oslo on 28/11/2010
Lecturer of Dr. Mette Johnsgaard, Lillestrom Helseklinikk, Center for Treatment of Chronic Diseases:
Dr Mette Sophie Johnsgaard opened her speech by introducing Lillestrøm Helseklinikk, Center for Treatment of Chronic Diseases, where she is medical director. They see approximately 600 patients per month, most Norwegian patients, but also some Danish and Swedish patients visit the clinic, and lately patients have been contacting them also from the Continent. Today 3 physicians work at Lillestrøm, mainly with ME/CFS patients.
Dr Johnsgaard showed the audience the impressive list of her support group. Together with the two other physicians at the clinic, she has traveled extensively the last year, visiting several well known ME/CFS experts in order to learn as much as possible on diagnosis and treatment in patients with ME/CFS. This has enabled the doctors to find the best possible treatment plan for every individual patient.
She continued talking about the patient group in focus, especially what triggers disease and the amount of reactivating viruses and chronic infections, as this is information that can be important for treatment and also give a better understanding of the disease. She also mentioned gastrointestinal disorders including inflammation, bacterial overgrowth, parasite, inflammation and food intolerances. Both the chronic and reactivating infections and the bowel inflammation and persistent parasite inflammations are common in other retroviral disorders, making the XMRV story plausible.
Dr Johnsgaard honestly explained how a normal Norwegian GP has very little knowledge on retroviruses; neither HTLV nor HIV is often seen in a GPs office. This makes the connection between retrovirus and ME/CFS difficult to see, even after the positive studies showed possible connection to the disease. She told the audience how she was reluctant to send samples testing for XMRV virus until more was known on the matter, however, as  patients constantly kept putting pressure on the clinic, they finally decided  to send  samples to VIPdx, a CLIA certified laboratory. The positive samples came as a big surprise to both doctors and some patients, and the need for Norwegian research seemed obvious.
She continued explaining how many samples where positive in cell culture and/or serology, and showed connections between Karnofsky score and positive samples. The material is of yet not published.
Dr Johnsgaard showed us a couple of patient examples. 2 co-workers got sick about the same time with a hard influenza-like disease. One developed a chronic neurological pain disorder but no exhaustion, the other a classical ME/CFS. They are both XMRV positive.  A patient develops ME/CFS after an accident, but had bouts of chronic sinusitis and tendinitis years before the accident.  The house proved to have molds and she could pin point many symptoms having started as she moved into the house. After renovating the house, she has experienced a great improvement on biotoxin therapy as used by Dr Ritchie Shoemaker, with whomDr Johnsgaard is in close contact with. The patient does however also have positive XMRV.
Here is the conclusion to the Dr. Johnsgaard’s experience at Lillestrøm helseklinikk so far:
-          Many different triggers give the same disease
-          Chronic infections and reactivated viruses are common and need treatment
-          Many patients have gastrointestinal disorders that can be treated
-          Many patients have biotoxin disease that can be treated
-          Clusters of ME/CFS are seen in families and areas
-          Partners do and do not get sick
-          There is an overweight of cancer and autoimmune diseases in the family of patients with ME/CFS
-          Varying effect on treatment protocols makes it important to have individual, tight follow up
-          Many patients get better after treatment up to a certain point, pointing to the possibility of treating secondary effects in a retroviral infection.
What can be treated to day:
-          Chronic / reactivated infections
-          Gut inflammation
-          Biotoxin disease
-          Inflammation
-          Immune pathologies, to a certain degree
It is too soon to try anti retroviral treatment. More research is needed.
Dr Johnsgaard continued her speech talking about the ongoing research: “NO-CFS, stage 1, confirmatory study for the detection of gamma retrovirus related sequences”. The research is being conducted in cooperation with the WPI, USA and the San Raffaele Scientific Institute in Milan, Italy. She also mentioned several planned research projects planned for 2011, including research in biotoxin disease in cooperation with Dr. Ritchie Shoemaker and bigger international studies for human gammaretrovirus.
Dr Johnsgaard’s speech was constantly pointed back to the patients, and at this point she talked about two patients she has been treating. The first was a young girl who was extremely sick without any offered treatment nor explanation for her ME/CFS symptoms. After one year of treatment she is back to normal life. The other, a young boy has been bedriddenfor years, mysteriously extremely ill.  He is so sick that he cannot interact with even his parents without it being a great strain for him. He has told his mother he plays in the garden with his friends inside his head. That is all he can manage. No treatment has had any effect so far, and Dr Johnsgaard pointed out that the extremely ill patients are one of the major reasons she feels research is so important. He is also one of the reasons why it is so important to ban blood donations from ME/CFS patients. If there is the slightest chance that a transmissible agent can lead to such a debilitating disease, one should stop any possible route of transmission.
As a summary Dr Johnsgaard showed off the following slide:
·         ME is a serious disease. It reduces life function more than most other diseases seen in a GPs office. It is also a great burden on society.
·         We know through research that ME/CFS patients have reactivated viruses and chronic bacterial infections
·         We know through research that ME/CFS patients have immune pathologies
Concerning retrovirus:
·         We know XMRV is a novel human gamma retrovirus
·         We know HTLV is associated with cancer and inflammatory diseases
·         We know HIV is associated with severe immune deficiencies
·         We believe XMRV is related to certain types of cancer
·         We believe XMRV is related to a chronic immune inflammation
·         We believe XMRV is only one of several gamma retroviruses that will be isolated over the   next years, opening up for the possibility for explaining different degrees of severity in patients with ME/CFS
·         We need more research, and for research we need funding
·         We need cooperation between researchers
·         Relevant research has to benefit patients without delay
·         We need an updated patient information channel 

Lillestrøm helseklinikk will continue to treat what is possible, and to follow up research.
http://www.lillestromhelseklinikk.no/  

XMRV, brought light/hope to CFS/ME Patients!=)

In 2009, Whittemore Peterson Institute scientists discovered a significant link between a newly-found retrovirus, xenotropic murine leukemia virus-related virus (XMRV), and the neuroimmune disease, ME/CFS. Their ground-breaking discovery was published in the world-renowned journal Science, on 8th October, 2010.
http://www.wpinstitute.org/xmrv/docs/wpi_pressrel_100809.pdf

http://www.sciencemag.org/content/326/5952/585.abstract?keytype=ref&siteid=sci&ijkey=m3wzKT4yJqEyk

This discovery brought renewed interest to the much-maligned disease and a flurry of research was conducted in order to confirm the link.

On August 23rd 2010, US government scientists validated the link, announcing they had found an association between a family of infectious murine leukaemia viruses and ME/CFS. They reported that 87% of those sampled carried at least one of the retroviruses, along with 7% (1 in 14) of the healthy controls.
http://www.rescindinc.org/fdanihpressconf.mp3

http://www.cfscentral.com/2010/08/fdanihharvard-xmrv-study-same-thing.html

http://www.pnas.org/content/early/2010/08/16/1006901107.full.pdf+html

http://www.pnas.org/content/early/2010/08/16/1007944107.full.pdf+html

XMRV is similar to HIV, the retrovirus that causes AIDS.

Following the validation study several countries banned ME/CFS patients from giving blood. In many cases these bans are for life.

For more information on XMRV and the Whittemore Peterson Institute, please visit the following site: http://www.wpinstitute.org/

If you would like to donate a regular, small amount to help push this research on, then please consider participating in the COUNT ME IN campaign. For more details visit: http://www.facebook.com/note.php?note_id=160913563956987

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Key Scientific Papers & Related:

Detection of an Infectious Retrovirus, XMRV, in Blood Cells of Patients with Chronic Fatigue Syndrome Science http://www.sciencemag.org/content/326/5952/585.abstract?keytype=ref&siteid=sci&ijkey=m3wzKT4yJqEyk

Detection of MLV-related virus gene sequences in blood of patients with chronic fatigue syndrome and healthy blood donorshttp://www.pnas.org/content/early/2010/08/16/1006901107.abstract

Aug. 23, 2010 – Detection of MLV-related virus gene sequences in blood of patients with chronic fatigue syndrome and healthy blood donors PNAS FDA Press Briefing http://www.wpinstitute.org/news/docs/FDAbriefing_082310.pdf


Blood Donor Bans:
http://mcwpa.org/in-the-news/blood-donor-bans/


Pertinent News & Blog Reports:

A Big Splash From an Upstart Medical Center New York Times http://www.nytimes.com/2009/11/12/giving/12SICK.html

New Hope in Fatigue Fight Wall Street Journal http://online.wsj.com/article_email/SB10001424052748703846604575447744076968322-lMyQjAxMTAwMDIwMzEyNDMyWj.html

Viruses Found in Chronic Fatigue Syndrome Patients – National Institute of Health NIH Research Matters http://www.nih.gov/researchmatters/august2010/08302010chronicfatigue.htm

The Lingering Mystery of Chronic Fatigue Syndrome http://well.blogs.nytimes.com/2011/01/03/the-lingering-mystery-of-chronic-fatigue-syndrome/?ref=health

Exhausted by Illness, and Doubts http://www.nytimes.com/2011/01/04/health/04fatigue.html

XMRV and CFS – It’s not the end http://www.virology.ws/2010/12/22/xmrv-and-cfs-its-not-the-end/

Gearing Up for the Big Search for XMRV http://blogs.wsj.com/health/2010/11/17/gearing-up-for-the-big-search-for-xmrv/


Other XMRV Links:

Cleveland Clinic - 40% of patients with aggressive prostate cancer have XMRV http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.0020025

XMRV: Virological, immunological and clinical correlations in patients with chronic lymphocytic leukemia and mantle cell lymphoma http://www.wpinstitute.org/news/docs/Snyderman_XMRV.pdf

Xenotropic Murine Leukemia Virus–related Gammaretrovirus in Respiratory Tract http://www.cdc.gov/eid/content/16/6/1000.htm

COMPOSITIONS AND METHODS RELATING TO XMRV-RELATED DISEASES AND CONDITIONS http://www.wipo.int/pctdb/en/wo.jsp?WO=2010132886&IA=US2010035144&DISPLAY=DESC

Of mice and men: on the origin of XMRV http://www.frontiersin.org/virology/10.3389/fmicb.2010.00147/abstract

XMRV retrovirus found in 62% of ME patients tested in Lillestrøm, Norwayhttp://esme-eu.com/news/xmrv-retrovirus-found-in-62-of-me-patients-tested-in-lillestroem-norway-article440-7.html

THE PREVALENCE OF XMRV IN HEALTHY BLOOD DONORS IN JAPAN http://www.diagnosesupport.com/health/index.php?option=com_content&view=article&id=305%3Athe-prevalence-of-xenotropic-murine-leukemia-virus-related-virus-in&catid=132%3Axmrv-research&Itemid=8

1st International Workshop on XMRV: Abstracts in Reviews in Antiviral Therapy & Infectious Diseases 2010_8. Abstracts http://regist2.virology-education.com/abstractbook/2010_8.pdf

Distribution of xenotropic murine leukemia virus-related virus (XMRV) infection in chronic fatigue syndrome and prostate cancer Pubmed.gov http://www.ncbi.nlm.nih.gov/pubmed/20842203?dopt=Abstract

A Third Pathogenic and Lymphotropic Human Retrovirus AIDS Reviewhttp://www.aidsreviews.com/files/2010_12_2_121-123.pdf