This information is reproduced with kind permission from the Nov 2009 issue of Dr. Bell’s free Lyndonville News e-newsletter – published after the watershed CFS Advisory Committee Meeting in Washington, DC, October 29 & 30. Dr. Bell highlights key points made in the XMRV-focused meeting & introduces related projects the revived Lyndonville Research Group already has underway.
Introduction: Public Lecture, December 6, 2009 in Batavia, NY on XMRV and ME/CFS
Because of the enormous interest generated, I will be giving a talk on the XMRV virus and what is known about its relationship to ME/CFS on Sunday, December 6, 2009. The talk will take place from 2 pm to 5 pm at the Holiday Inn of Batavia NY (8250 Park Road, Batavia, NY, 14020), right next to the NY State Thruway. The location was chosen because it was roughly equidistant from both Rochester and Buffalo, and the presence of rooms at a reasonable cost ($80) for those persons wishing to stay overnight. There will be a $10 per person charge at the door to cover the costs.
In this lecture, material will be presented from:
• The Science paper,
• Dr. Dan Peterson's testimony at the CFS Advisory Committee meeting,
• And our hopes for a study to help confirm these findings.
I will also share my opinions about treatment options that may open up in the future.
XMRV – "The Important Part"
In the CFSAC meeting October 29, Dr. Dan Peterson filled in several blanks. [Find his presentation, beginning 10:15 am on Oct 29, in the NIH’s VideoCast archive – http://videocast.nih.gov/PastEvents.asp.] I will present much of what he said at the lecture December 6th. But here is the important piece:
XMRV DNA was found from 68 of 101 patients (67%), and this was in the Science paper. That leaves 33 patients with CFS who were negative. But on further testing, 19 of these 33 are XMRV antibody positive, 30 of these 33 had transmissible virus in the plasma, and 10 of these 33 had protein expression. Overall 99 of the 101 patients show evidence of XMRV infection.
These results have interesting implications.
The most important is that there is not a simple test now that will tell you if you have XMRV or if the virus is active in your system. And we need a good control study using all three measures to accurately know control presence of the virus. This is not a fly-by-night operation. Right now, it is necessary to do several tests to know the XMRV status:
a. DNA by PCR [polymerase chain reaction],
b. Viral infectivity,
c. Detection of viral proteins,
d. Antibody to the XMRV envelope.
As time goes on and we learn more, this process will be simplified. What I do not want is poor science that will cast doubts on an illness that already has its fill of doubters. Let’s do it right from the beginning. If by doing it right XMRV proves not to be the cause, so be it. Something is the cause.
He is a true veteran (45 years) of retroviral research. There have been comments from various people saying that there are lots of viruses associated with CFS, so what is the big deal? Among the points raised by Dr. Coffin:
a. It is relatively difficult to isolate live retrovirus from patients with HIV infection, but relatively easy to isolate live XMRV in CFS. There is a high percentage of infected cells.
b. The percentage of positive controls for XMRV is not that much different between CFS controls and prostate cancer controls, 4% or 5%. However, much work needs to be done to verify the control incidence. This is particularly true because the nation’s blood supply could be contaminated. (By the way, no patient with ME/CFS should donate blood – personal opinion.) The Japanese Red Cross has said that there is a "low incidence" of XMRV in their blood supply.
c. Could some mouse have contaminated the tests by shedding some XMRV in the lab? XMRV is a big family of "simple" retroviruses. In the XMRV strains isolated in CFS patients there is a 0.3% diversity from what are carried in mice – a relatively large diversity. This virus does not vary with replication as much as HIV does. In two weeks of HIV replication the diversity is greater than 0.3%. And this is both good and bad news. Good news for the ultimate production of a vaccine. The diversity has been a roadblock in the production of a HIV vaccine. Bad news for the antiviral therapy implications. But that is way down the road.
d. Dr. Coffin presented a slide of the many things we do not know about XMRV. There are lots of things to do.
e. Dr. Coffin mentioned that there is excitement in the retroviral scientific community – very good news for the ME/CFS community. We will get confirmation, or lack of confirmation, from many good scientists. It will be difficult for biased scientists to squelch this, if it is, in fact, true.
The statement that made my socks roll up and down all by themselves was a reply to a question from the committee. Dr. Coffin said "This was as good as it gets for a first paper, but it is still just a first paper."
Theory of Mechanism of XMRV and ME/CFS
Dr. Peterson presented an update of a theory of mechanism that has been circulating for many years. Ironically enough, it was once called the "X factor theory."
Step 1: Infection with XMRV. No idea of how this happens. Could it be that the tiny XMRV piggybacks onto some huge, lumbering herpes virus like EBV, or HHV6? That mechanism is known to occur. Lots of other possibilities.
Step 2: Infection of B, T lymphocytes and Natural Killer cells. Dr. Klimas has said that up to 70% of lymphocytes are "activated." Something is going on.
Step 3: Impairment of NK cell number and activity. Because of the retroviral infection, the NK cells are impaired. This is parallel to what is known to happen in HIV disease with the CD4 lymphocytes.
As a result of poor NK cell number and function (and other T & B cell problems) the person now has an immunodeficiency. NK cells are important in the control of herpes viruses and other agents.
Step 4: Reactivation of other agents. Increased viral load of EBV and other agents cause cytokine production, activation of 2'-5'A Synthetase, RNAse L which contribute to symptoms.
It is interesting to note that AIDS patients feel better with suppression of secondary infections. This could explain why treatment with antibiotics, antivirals, gamma globulin and other agents make some patients with ME/CFS feel better for a while.
History [and Predictions]
It is my personal opinion that Dr. Daniel Peterson's presentation at the CFSAC 10/29/09 [http://videocast.nih.gov/PastEvents.asp] is history in the making. Time will tell.
And while I am making rash predictions, let’s talk about the name of this illness. It has been a favorite topic of mine since the "Disease of a Thousand Names." [Book by Dr. Bell, CFIDS: The disease of a thousand names, now out of print.] Chronic fatigue syndrome is a miserable name.
I think that XMRV is going to turn out to be the puppet-master that pulls the strings of illnesses variously called CFS, ME, fibromyalgia, atypical multiple sclerosis, chronic mononucleosis…. And if it does, the name should be XAND, for Xmrv Associated Neuroimmune Disease. I heard Mrs. Annette Whittemore use this term and it feels right. History.
Lyndonville Research Group Report
The LRG is back in business. A couple of phone calls, a pizza, and we are off again. I think that is the definition of a grass roots organization. We have four projects listed and have begun working on them.
Project #1 is the lecture in Batavia on December 6 at 2 p.m. I anticipate the talk will be about 1 hr to 1 ½ hours, then a break, then questions until 5 p.m. The rental of the conference room is reasonable, and it holds 400 people. I think now is the time for communities to get active again, and I will be happy to present this talk to any community, providing a local group or individual pays airfare and lodging. It might be a good way to get support groups active again.
Project #2 is to begin organizing support for the New Jersey NEI center and their satellite branch in western New York. If I did not have to run the business, I would be happy to see patients with CFS in western New York.
Project #3 is important. It is now 25 years since the outbreak in Lyndonville, and we are tracking down the 60 kids who got ill at that time to find out what has happened to them. When the 15 year follow-up study was published (Bell D, Jordan K, Robinson M. “Thirteen-year follow-up of children and adolescents with chronic fatigue syndrome.” Pediatrics, May 2001;107:994-8), 20% of the kids in that study were still sick, but what is happening now? We'll see.
Project #4 is perhaps the most important of all.
– Did XMRV cause this cluster outbreak? If so the 60 kids should have demonstrable exposure to XMRV.
– Does this virus cause some to stay sick? If so, we should find viral DNA and viral proteins showing replication in those still sick, but not in those who got well.
In the past people have asked if they can make contributions and I have always declined. But we will now welcome any contributions to the Lyndonville Research Group.
These contributions will help pay for sample and questionnaire mailings, blood collecting equipment, tubes, pizza, and conference expenses. No volunteer will be paid, including myself, and if there is any extra money kicking around, I will make sure it gets to the WPI or other worthy cause. The expensive stuff, meaning testing for XMRV, will be paid for through WPI or other organizations.
Contributions can be sent to myself at 12851 Roosevelt Highway, Lyndonville, NY 14098. The Lyndonville Research Group is not tax exempt, but there is a local charity that is tax exempt and can be used. Questions may be directed to myself at Lynnews@davidsbell.com.
There were many questions about getting tested for XMRV.
Answer: I am reluctant to suggest to anyone that they spend big bucks for a commercial test now. We do not know if a particular test is accurate, and even if it is accurate we do not know what it means, and even if we did know what it meant we would not know what to do with it. I would be patient. Answers will start flowing soon, so stay tuned.
– Dr. David S Bell, MD
Contact: If you wish to contact Dr. Bell, e-mail to firstname.lastname@example.org; very few inquiries are answered, but comments are welcomed.
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Disclaimer: Any medical advice that is presented in the Lyndonville News is generic and for general informational purposes only. ME/CFS/FM is an extremely complex illness and specific advice may not be appropriate for an individual with this illness. Therefore, should you be interested or wish to pursue any of the ideas presented here, please discuss them with your personal physician. © 2009 David S. Bell