Rituximab: The Big Guns For ME/CFS

I appreciate all the good wishes I’ve received from readers. I want to assure everyone that the anonymous personal attacks don’t really bother me. It comes with the territory for hanging it out there as I have. I chose controversy consciously. This type of harassment is what happens when you step out of line and threaten the status quo. I actually kind of like the free-for-all in some ways. It lets us know what we are up against. Too much agreement makes for complacency. To people who have written that it makes you sick, please don’t internalize it. I don’t. I suspect the harassment is in fact a very few individuals. Don’t let it get you down. I do think things will calm down a bit now naturally, since I don’t foresee a great deal of retrovirology forthcoming on our behalf in the near future. I anticipate the discussion will now turn to treatment and how best to live with the disease. We should be on much more stable ground, since it is much harder to take pot shots at my medicine than my retrovirology. I’m sure someone will try though; wouldn’t it be wonderful if the criticism was considered rather than knee jerk?
The little mystery play we just witnessed, courtesy of Jason, exemplified the pitfalls of science as a religion unto itself. Operating under the guise of “science” creates a safety net for its practitioners, satisfying the need for self-aggrandizement, simultaneously providing excuses for not going the extra distance to look outside the box. Very much the same as the medical profession. The Health Director of Norway just apologized to patients for decades of neglect and abuse. I’d like to see a similar apology from the Surgeon General of the USA. An apology tied to some serious restitution. 
Personally, I was abused in every way possible due to CDC/NIH incompetence, from being unable to find adequate care to being denied entitlements, private disability to the SSDI system, all compounded by incompetent doctors, lawyers and now scientists. When I was first disabled in 1995, I had occupation specific disability insurance through Provident, meaning, if I couldn’t be an ER doctor, they had to pay, even if I could be some other kind of doctor, $6000/month for life. They harassed me with IME’s and other invasions into my life, literally forced me into psychiatric treatment I didn’t want, until I settled with them. For the sake of entertainment and telling the whole story, though it has no bearing on the discussion, my lawyer stole the money; he went to jail, after I spent a bunch more money to expose him, but I never recovered what he stole. When I was disabled the second time, I didn’t apply for SSDI right away, because I couldn’t believe I wasn’t going back to work. I applied after my first near death experience at our local Santa Fe hospital, with a thousand pages of records. But it turns out my last “date of insurability” was before that, so it was over before I knew I needed to build a case. Since I didn’t have a correct diagnosis for 15 years, I’m completely screwed, case sitting in appeal for 2 years as I write this. All because I didn’t have a diagnosis. And the new ICC wouldn’t have helped. It is coming to light now, that although I didn’t know what was wrong with me, Provident, in fact, did know. There is a class action suit about those policies, sold before so many yuppies were becoming disabled early in life, but since I settled, I can’t participate. A cluster fuck, as they say in the military. 
The observations that my behavior is not in line with what is considered “professional” has me thinking about what professionalism means to me now that I am reinventing myself yet again. According to Wikipedia, the criteria for a professional are: 
  • Expert and specialized knowledge in field which one is practicing professionally.
  • Excellent manual/practical and literary skills in relation to profession.
  • High quality work in (examples): creations, products, services, presentations, consultancy, primary/other research, administrative, marketing, photography or other work endeavors.
  • A high standard of professional ethics, behavior and work activities while carrying out one’s profession (as an employee, self-employed person, career, enterprise, business, company, or partnership/associate/colleague, etc.). The professional owes a higher duty to a client, often a privilege of confidentiality, as well as a duty not to abandon the client just because he or she may not be able to pay or remunerate the professional. Often the professional is required to put the interest of the client ahead of his own interests.
  • Participating for gain or livelihood in an activity or field of endeavor often engaged in by amateurs b : having a particular profession as a permanent career c : engaged in by persons receiving financial return.
  • Reasonable work morale and motivation. Having interest and desire to do a job well as holding positive attitude towards the profession are important elements in attaining a high level of professionalism.
  • Appropriate treatment of relationships with colleagues. Special respect should be demonstrated to special people and interns. An example must be set to perpetuate the attitude of one’s business without doing it harm.A professional is an expert who is master in a specific field.

I admit to difficulty with the last two at this point in my career. My disgust with most physicians and ‘the profession’ is profound and being ‘appropriate’ is low on my list of priorities. But I certainly can live by the rest of it. Personally, I would have been better off with a good village witch doctor than any of the so-called professionals who ‘took care’ of me for the first 15 years of my disease, all of whom did great harm to my mind, body and spirit. In fact, one of my goals in life is not to need a doctor or a lawyer:).

In general, CFS patients get better care if they don’t tell doctors what they have. Many patients have told me this. Have chest pain or a belly ache and need to go to the ER? You will get better care if you just talk about the chief complaint. Sad, but true. Maybe it is finally changing? XMRV, however it plays out, has brought us into the spotlight at last. We are finally worthy of study, not only because of numbers of affected people, but because maybe, just maybe, we are sick. And not because of our wrong thoughts. We don’t tolerate stress, because we have diffuse hormone receptor insensitivity and depletion, including stress hormones. The response to stress is abnormal, and not because of distorted thinking. Viruses hi-jack cellular machinery, and retroviruses do it on an evolutionary level, using the organism’s own DNA to replicate, either by reverse transcription and assembly of new viral particles or mitotically. Stress is an inevitable consequence of life, and some retroviruses have evolved a strategy to take advantage of this, hormone receptor elements that, when activated, turn on virus: Glucocorticoid Regulation of Murine Leukemia Virus Transcription Elements Is Specified by Determinants within the Viral Enhancer Region. Celander. Note interesting evidence that steroid responsiveness of MLV’s may be competitively inhibited by progesterone.

And now we have the Rituxan study from Norway:

An unintended effect of treating a patient for cancer was remission of CFS symptoms and the patient’s doctor actually noticed. The entire CFS community owes the doctors who pursued and published their study a debt of gratitude. Whether Rituxan pans out for CFS or not, Drs. Fluge et al gave CFS patients big guns, and reported scientifically (though blinding doesn’t seem possible since the patients could probably mostly tell who got the drug).

Rituximab is not the only chemotherapeutic drug to result in temporary remission of CFS symptoms. The question is why and who might be helped by it enough to justify the risk. Given that it is possible to die from a trial of the drug, it isn’t an academic question, or mostly about money and politics, as with arv’s. If you want to look at the disease as an immune disorder of unknown etiology, rituximab, might help a subset of patients by depleting CD20 expressing B cells. However, even for rheumatoid arthritis patients, 40% or so don’t respond to B cell depletion, even though B cells are clearly involved in the pathogenesis of that disease. Rituximab also selectively depletes certain T cell and NK cell populations. Most cytokines/chemokines are made by T-cells, but under certain circumstances, B cells make proinflammatory cytokines also. Here are some hints:

And the argument against: The drug cripples immunologically on purpose and we may be more at risk than rheumatoid arthritis patients for the worst possible outcome:

Take a look at this paper, addressing the question of why some RA patients respond to B cell depletion and some don’t: New Insight in the Mechanism of Action of Rituximab: The Interferon Signature Towards Personalized Medicine. Verweij. It suggests that particular levels of gene expression, disease phenotype, low IFN signature, predicts response to treatment. This paper also talks about the effect of the drug on macrophages, shifting them to a more mature, less proinflammatory stage, possibly suggesting some mechanistic overlap with the positive clinical effect observed in some patients with GcMAF. Since a course of treatment, 2 infusions 2 weeks apart, costs $9000, generally needs to be repeated every 6 months, and includes significant risk of morbidity/mortality to the patient, it is important to predict response to treatment. There are over 8000 papers on PubMed about rituximab (a search for ‘chronic fatigue syndrome’ brings up 5430 papers). The arthritis literature seems to find the risk acceptable. The risk of hypotension, anaphylaxis from the infusion itself, can be ameliorated with skilled administration and/or concurrent treatment. The increased risk of infection, deemed mild to moderate, in the arthritis literature, is anecdotally significant, according to doctor friends of mine who have treated complications of the drug. There is a small risk of sepsis, fulminant hepatitis B reactivation and PML (progressive multifocal leukoencephalopathy). It does appear that the risks decrease for a particular patient with time, though the longest patients have only been followed for 5, to at most 10, years. Longterm Safety of Patients Receiving Rituximab in Rheumatoid Arthritis Clinical Trials. Vollenhoven.

Although I am enthusiastic that someone is talking about big guns for CFS, my initial reaction was, I’ll sit this one out until we know a lot more. It scares me. But when I answered Ali’s questions about why I’m not more interested, she said, “I’d take a small risk of death every 6 months for a complete remission.” So Russian Roulette. I have a patient with a high Rheumatoid Arthritis Factor, degenerative arthritic changes on MRI and clinical synovitis. She could probably get it covered, a problem for most CFS patients. Though I wouldn’t prescribe it at this time, this patient could seek treatment from any number of rheumatologists who have vast experience with the drug.

Dr. Michael Snyderman’s comments of this morning:

In my practice, rituximab at 375mg/m2 causes hypotension in most patients, about 60% need downward adjustment of their infusion rates and about 25% the hypotension is severe enough to be symptomatic. I would expect the hypotensive reactions to be more severe and frequent at the dose of 500mg/m2 used in the CFS protocol. If the patients signed a proper consent form they would have been warned that hypotension would be a risk, therefore most patients would be aware that they had received rituximab rather than placebo. The physicians who administered the rituximab would have to be adjusting the infusion rate in most patients and would also be aware that they had given the active drug rather than the placebo.

Therefore the statement that the study was double blinded is incorrect; it is not possible to double blind rituximab for the above reasons. Furthermore, the results are based on subjective, “how do I feel” criteria which could be influenced by the patients knowledge that they had received rituximab. We have not proven that there is an expansion or clonal component of B-lymphocytes in CFS. There may be but it has to be proved and we have just started looking on a small scale. I believe that the MLRVs (I know this is politically incorrect nomenclature) probably integrate into a number of cell types. I and other people with CFS and cancer have clonal gamma delta T-cell expansions. Gamma delta T-cells are a more likely source of the well-known and accepted elevation of cytokines/chemokines in CFS than B-cells. I could find very little about cytokine/chemokine production by B-cells, certainly with respect to those elevated in CFS. I did a search as to the origin of IL8 and could only find that neutrophils and “macrophages” which would be derived from monocytes could make IL8. I could not find any article saying that B- or T-lymphocytes made IL8 but maybe they do, the area needs more research.

With respect to the present preoccupation with B-cells in CFS all I have seen were nebulous references to autoantibodies. What are the autoantibodies that cause CFS? This is too much of a leap of faith for me. Finally, rituximab would have no activity against the T-cells that are responsible for elevated cytokines found in many patients with CFS.

It maybe that CFS patients have a veritable zoo of clonal cell lines that interact with each other. I would not be surprised at all if there was a clonal expansion of cells derived from monocytes in CFS. Monocytes are the source of macrophages and microglial cells. This would fit Dr. Sandra Ruscetti’s belief that microglial cells are part of the problem with CFS. So, MLRV would integrate into monocytes, increased levels of IL8 would be made and rogue microglial cells would cause problems in the CNS. Rituximab would have no activity against monocytes or microglial cells.

Rituximab is very immunosuppressive and patients who receive it are at risk for opportunistic infections including the dreaded progressive multifocal leukoencephalopathy which is caused by the JC polyoma virus. I hope to soon prove that I have a unique MLRV (not “XMRV”) and it therefore doesn’t make sense to me to take an immunosuppressive drug. In conclusion, we need new treatment for CFS but for many reasons I don’t think that rituximab will be useful. 

Occam’s Razor, as applied to medicine, advocates looking for diagnostic parsimony, though patients may of course have more than one disease; the subsets of patients I think related, e.g. treatment refractory Lyme Disease and ME/CFS, may in fact have different diseases. In any case, it is a big step up to have an immune disorder rather than a psych disorder. But with respect to an explanation for all the manifestations of the disease, plus the epidemiology, I still think a retroviral hypothesis fits best. Clonality contributing to pathogenesis fits. MLV’s replicate mitotically, by clonal expansion, in addition to conventionally (as does HTLV). This is a likely explanation for the incomplete response to arv’s in people with advanced disease. The little bit of information that we have about this in CFS suggests that clonal expansion can happen with various cell lines, so B cells might be implicated in some patients, but T cell clonality more important in others. LabCorp has testing to look at both T cell and B cell clonality (southern blot and PCR).

Epigenetic factors are clearly a very important piece of the clinical picture, likely impacting who gets sick and who doesn’t. Here is an excellent article to start the discussion, illustrating where the environmental piece comes into play. As I’ve said before, I think environmental and retroviral illness are two peas in a pod, not in any way mutually exclusive hypotheses. Why Your DNA Isn’t Your Destiny. Cloud.

Silverman found that XMRV induces 30 genes in vitro within 24-48 post infection. This is the kind of quality work that isn’t being done on our behalf, because XMRV is dead. For posterity, please reread Lee/Silverman. Journal or Urology. Vol 185, No. 4S, Supplement, May 15, 2011 :

EPIGENETIC REGULATION IN INHIBITION OF PROSTATE-DERIVED ETS FACTOR, A TUMOR METASTASIS SUPPRESSOR, IN ADVANCED PROSTATE CANCER A TUMOR METASTASIS SUPPRESSOR, IN ADVANCED PROSTATE CANCER Joshua Steffan, Sweaty Koul, Randall B. Meacham, Hari Koul*, Aurora, CO INTRODUCTION AND OBJECTIVES: There is, at present, no effective treatment for intervention in metastatic prostate cancer. In our recent studies we demonstrated that Prostate-derived Ets factor (PDEF) expression is decreased, and even lost in high grade prostate cancer. Using in vitro assays we show that reintroduction of PDEF results in phenotypic reversal from aggressive to a less morbid pheno- type in prostate cancer cells. Since a common mechanism of tumor suppressor inactivation is by promoter hyper-methylation, the objective of this study was to determine if and how PDEF is regulated epigeneti- cally through promoter methylation. METHODS: LNCaP cells (Androgen dependent), LNCaP C4-2B (Androgen un-responsive) and PC3 (Androgen independent) prostate cancer cell lines were maintained in their respective growth media supplemented with 10% Fetal Bovine Serum and antibiotics. PDEF was over-expressed using bicistronic vectors and delivered by retroviral transfection. Where indicated cells were pretreated with 5-aza cytidine (5-azaC) for various time points prior to measurement of PDEF expression by RTPCR method. Cellular RNA was isolated, reverse- transcribed into cDNA, and PCR was performed using PDEF-specific primers. Migration (scratch assays and Boyden chambers without Matrigel) and invasion (Boyden chambers with Matrigel) were per- formed on cells treated with or without 5-azza-2’-deoxycytidine. RESULTS: We observed decreased PDEF expression in pros- tate cancer cell lines correlated with increased aggressive phenotype, and complete loss of PDEF protein in metastatic prostate cancer cell lines. Treatment of prostate cancer cells (PC3 cells) that do not show any PDEF expression with DNA methyl transferase inhibitor, 5-azaC, led to expression of PDEF in a time dependent fashion, suggesting epigenetic mechanisms in suppression of PDEF in advanced prostate cancer. Our studies suggest that treatment with 5-azaC results in decreased cell migration and invasion, concordant with an increase in PDEF expression. CONCLUSIONS: These studies demonstrate for the first time that inhibition of PDEF expression in aggressive prostate cancer cells is modulated by epigenetic mechanisms. Based on these exciting results, we propose that epigenetic regulations are critical for progres- sion of prostate cancer to aggressive phenotype and that demethylating agents like 5-azaC may serve as effective agents to prevent prostate cancer progression. 

Since XMRV is dead as a human pathogen it makes no sense for the Lipkin study to use precious specimens collected at a cost to the taxpayers of $450,000 ($1500/specimen to the doctors for each patient and control, 150 of each) to allow WPI to try to prove that they can do what they already proved they couldn’t do, and now without a chief scientist. It seems to me that the patient community should object to that vociferously. Rather, the rest of the money should be spent on deep sequencing, looking for the actual cause of the disease. Why not allow Dr. Lipkin to look? He said in Reno that if someone gave him a million dollars he’d look. Let the virus hunter hunt look for it, not Unevx. What if they don’t find it? Then it’s really dead. It is most definitely not in our best interest to give them another shot. They should sink or swim on their own, not spending the very few tax dollars earmarked for investigating causation in our disease. We should certainly not be willing to have the WPI be our last best hope at this point.

I thought this article particularly interesting while we consider where our disease came from: Canadian researcher traces AIDS to single bush hunter from 1921. The scientific community is showing a stunning lack of concern with respect to live vaccines and other medical technology known to be contaminated with animal retroviruses. The case is growing. Too many clues. The burden of proof is on the folks selling the stuff. A little humility, in short supply in the past, is certainly in order now. The band is playing on again.

Today’s song: I Won’t Back Down
Did you like this? Share it:

94 thoughts on “Rituximab: The Big Guns For ME/CFS

  1. >The beneficial effects of rituximab seem to centre on its ability to reduce the production of Th17 cells and elevate T regs( foxP3) as well as inhibiting Nf-kappaB. The same end result could be achieved via the use of an ACE2 inhibitor bezafibrate and IV curcumin ( oral curcumin has almost zero bioavailability)

  2. >sorry I forgot to mention that much of the pathology caused by the gammaretrovirus that causes murine aids is caused by the integration of the virus lp-bm5 def into B cells and promoting clonal expansion. Deleting B cells would be expected to reduce viral titre. The autoimmune "arms" of ME could well result from the elevation of NF-kappaB and the induction of a Th17 profile which result from activation of microglia a typical MO of a MLV

  3. >As always, you convey important and complex issues with clarity; you are always a pleasure to read. Relative to the Norwegian study, I wonder if we are putting too much emphasis on one part of the tale. Maybe it's not the drug's efficacy or risks that are the story, but what it demonstrates. The immune thing is a decades old one, but who cares if it can realize traction now with the media and climb into mainstream conversations? I am all for fighting for what I believe to be the root of my disease, but I'd exchange that indulgence for the same status as an MS sufferer, certainly at least in the short term. This Norwegian study could provide that platform if we can position it, coax it forward. Not an easy proposition. But we also have a major government agency issuing us an apology. Now that is quite a tandem. Should we not be embracing this and running with it as if we don't have HGRV's on the stove simmering as the cause? Maybe we dont have to demand all or nothing; maybe we just manuever for it. Get our respective governments (I know you've an international following) to acknowledge the organic nature of our disease without forcing the cause hand until it is so strong, through deep sequencing data hopefully, that they cannot deny it.

    Just a thought. Regardless, thank you for representing me and my concerns on the front lines, and for taking the flak in my stead.

  4. >After decades of being sick with cfs/me my daughter is now begging to commit suicide. There is no doubt in my mind that my daughter would risk death every six months to have a chance to feel well. I know we don't like to talk about suicide but I have to struggle with her desire fairly often now like a fire that has to be put out. Waiting another 5 years till treatment is going to be an eternity. She used to be so happy before getting sick. Help has to come sooner than 5 years.

  5. >WPI need to relinquish the grant so NIH can give it to Dr. Mikovits. She can then finish the deep sequencing somewhere else. If they don't I will remove myself rather than have the WPI waste any taxpayers dollars. Also I wonder exactly what was the Chase and Vivent money used on? Patients expected it to go to Judy's research. Where is the accounting of the money as well as the private donations? What was all the contest money spent on? This is money that patients sent in, and contests that they voted on for Judy's research. WPI is still not giving any answers. And as far as the Rituximab studies goes. I guess any recognision that our illness is serious is probably better than being called crazy for 30 years or so. And we can thank Fauci, Wessely, the CDC, the CAA and a few others for that label. Also in knowing how HIV patients are more at risk for the JC polyoma virus complication while taking Rituximab, and given the fact I also carry an HGRV. I find trading the autoimmune label for a retroviral infection not a good consolation prize. And who is more happy about all this, but of course it's the CAA. Just think of the potential for income for them. Someone has to keep paying McKleary and Vernon's salary. To bad it's us.

  6. >Very good and thought-provoking post. You brought up so many issues I hadn't thought of, but some I am worried about.

    I think it's a good thing that the Norwegian oncologists made these connections. It does promote the autoimmune-disease point of view.
    (I'd give anything to see Wessley's face as he reads the news about the Norwegian studies.)

    This discovery should give ammunition with which to clobber the CFIDS-deniers.

    But I do want to know the cause of this anyway, as do others.

    I do have concerns about the drug companies' involvement in this situation, their basic money-making, rather than scientific interests.

    I am for watchful waiting to see what happens with this drug and also to see what Lipkin comes up with, and what happens with the other studies going on now.

    All of these discoveries can't help but bolster the cause for more research and funding — although this is a bad time for funding, as the Senate Super-Committee meets to come up with a way to cut $1.5 trillion from the budget, and where Medicare and Medicaid are going to be hit hard as well as research projects, I'm sure.

    Overall, I think it helps us with the physical cause argument. It's one more association that bolsters our case.

    I'll wait and see. The side effects bother me, as one of those who has had so many problems from medications, can't go near many or have to take small doses of anything.

    However, one thing I know: Your cognitive abilities are NOT affected by CFIDS, as shown in your very informative and well-thought-out post above.

  7. >You cannot assume a person has no cognitive difficulties based on an article. They manifest in numerous ways and patients learn to perform task so as to mask problems. You won't know for instance the time taken to write that, the help that may have been given or if it was proof read by another person.

  8. >Anon 6:30 PM,

    What an obnoxious comment! It took me 4 or 5 hours to write. Who do you think I have to ask for help:)? I wrote it and proof read it without assistance. As usual.


  9. >I don't think 6.30 was intending to be obnoxious – merely pointing out that the clarity of a person's written communication wasn't necessarily a fair measure of how cognitively affected they are by ME.

    Gerwyn…where and how does one obtain IV curcumin? Sounds intriguing.

  10. >Your post was excellent, and obviously written by you, a skilled, knowledgeable person.

    I am so glad you pointed out the worrisome things about Ritubimax.

    Even if it's an advance for general knowledge about CFIDS, and can be used to help researchers,and to help clarify this is a real physical disease, I really worry how many of us could actually use it.

    I have had so many bad scenarios from medications that it makes me nervous when these things come up.

    And I certainly do not think that words like "cause of mystery illness found," "successful treatment found for CFIDS," "cure-all for CFIDS," etc. I am concerned this will happen.

    Also, a general comment: We're off the XMRV discussion. Can everyone address the discussion here without this stuff?

    Some of us are ill and want to learn and discuss things like Ritubimax, which is now the "new topic for CFIDS." We're serious about the information, pros and cons — and all possible
    difficulties, pitfalls, etc.

    Not to mention cost. It's very costly to use, and with our health care cuts going on, who knows if it will even be available here for people who have certain types of health care coverage. But I'm putting the cart before the horse.

    A lot more needs to be learned first.

  11. >Thank you Jamie, for bringing up the Rituximab study. I looked the drug up and was certainly taken aback by the possible, some life threatening, side-effects. Since I suffer from pretty severe orthostatic intolerance, the mention of hypotension was particularly worrisome. I am also very sensitive to drugs in general and didn't think this was the one for me.

    However, it was heartening to hear that some physicians were willing to stick their necks out and mention the possibility of this or something like it helping ME patients. Let's hope someone will take this up and continue the research into finding something to help us. As the old saying goes, "I am sick and tired of being sick and tired!"

    Sharon D

  12. >Jamie,

    I think you own anon 6:30 an apology. He/she was trying to be supportive, saying that you could easily have cognitive difficulties despite writing a lucid blog. I know that I can often still write well despite having trouble with memory, concentration, and "brain fog" in general. It's sort of like the people who say "Well, you look well, so it's hard to believe you're really sick." In this case, "Well, you write well, so I can't believe you have any cognitive trouble." Anon 6:30 was stepping in to defend you, not to attack you. He/she wasn't assuming you have help with your writing, just saying we don't know what it's like for you to write it, so we shouldn't judge your mental or physical condition from your blog posts.

  13. >Well, Anon 9:28 PM, having been called stupid and insane here at one time or another, I did assume it was someone trying to discredit me, call me a liar. It is sometimes difficult to judge the intent with anonymous comments. I really wish people would identify themselves in some way. When I tried requiring commenters to sign in, it killed the conversation and I don't want that, but maybe a little extra consideration is in order. The unfortunate reality is that not everybody here is a friend.


  14. >Jamie, I very much appreciate where you are coming from ("having been called stupid in the past"). But when I read the comment by Anon 6:30, I really did feel him/her being supportive of you. I have moments of very frightening brain fog (where I can't even spell my name), but I also have moments where my cognitive function is somewhat ok and probably better than that of many healthy people. I really resent when people are trying to imply that I can't be all that sick just because they read something that was fairly cohesive, but took a very long time to write or was written during one of the rare better moments. Often, I do have somebody look over what I write before I put it out there just to make sure it makes any sense.

    I think it all depends on where our specific sensitivities lie: Mine are being perceived as being less limited than I am. Yours may be being perceived as less smart than you are–although I can assure that nobody who has been reading your blog would conclude anything other than that you are exceptionally smart.

    I just don't want you to push away somebody who is actually a supporter. We have enough enemies. We need all the genuine friends we can get.

    With much respect and gratitude,

  15. >Thank you, Jeannette. I'm sorry if I was touchy. I certainly know what you mean about the illness being minimized because it doesn't show. I guess right now, I'm sensitive for other reasons. I don't have brain fog. Other issues, but thankfully not that. I'm working, so I want that to be clear.


  16. >I also think it is important to note that many people who have a lot of brain fog can still work (mentally) quite well. I wouldn't hesitate to go to a professional with ME/CFS just because they might have brain fog. There was one study some time back of mental function in people with ME/CFS showing that they could do as well as "normals" on mental tasks, but that brain scans showed that their brains were working much harder than "normals'" brains to do the same tasks. I have sometimes joked that my brain gets such a work-out, plowing through the brain fog, that if I were ever suddenly to be well, I would be extra super brilliant!

    I have a lot of brain fog, trouble with memory, etc., but I still do many cognitive tasks as well as ever. I have to build in certain supports sometimes; for example, before my illness I never forgot anything, but now I forget a lot unless I write things down and keep lists. I still don't drop too many stitches in my life, but I have to use a different process than I used to.

    The one time my cognitive capacities fail me in a major way is when I am overdoing it. Then I can barely finish a sentence. But that's a useful sign that I should stop whatever I'm doing and get horizontal and quiet and recharge my batteries. Of course, by the time I'm feeling that "stupid," I might be too out of it to notice that I'm becoming incoherent. That's why it's helpful to me when a close friend or my husband is with me when I'm out and about–they know to watch for signs that I'm past my limit: facial flush, dazed look, speaking slowly or incoherently. Other people probably just think I've been drinking!!!

  17. >I agree with Anonymous statement,well said :

    "This Norwegian study could provide that platform if we can position it, coax it forward. Not an easy proposition. But we also have a major government agency issuing us an apology. Now that is quite a tandem. Should we not be embracing this and running with it as if we don't have HGRV's on the stove simmering as the cause? Maybe we dont have to demand all or nothing; maybe we just manuever for it. Get our respective governments (I know you've an international following) to acknowledge the organic nature of our disease without forcing the cause hand until it is so strong…"

    If this Rituximab study gives ME validation as a serious neuro-immune disease and it will give pharma an incentive to pump research money in to it, it will force health institutions (who are closely associated to the industry) to change their policies, than I think we "should take the deal" and ask the tough questions after.

    Tactically it would be a great mistake to try and undermine this study – because of the reason stated above ….

  18. >"Rather, the rest of the money should be spent on deep sequencing, looking for the actual cause of the disease."

    Sorry, but I'm going to quote Jason…


    Jamie, do you actually think there is only ONE cause of ME/CFS?

    Serious question.

  19. >I read the Chronic Fatigue Syndrome Advocate's blog post on Rituximab. He was talking about different research that's now going on. He said that there is probably a viral cause.

    Why don't we all wait and see what happens with the research that various people are doing?

    I think it's a good sign that the two Norwegian oncologists found that this drug helps to alleviate CFS symptoms, although not in everyone in the study nor for eternity; the effect petered out.

    However, it bolsters our arguments (and our own experiences and knowledge) that it's a physically caused disease. It could help the push for more research and funding. (And it might quell some of the CFIDS-deniers.)

    On brain fog, it's very curious. Sometimes I can write and am not forgetful (although I do write everything down). And then in the last few days I couldn't remember to get what I had to bring room to room, or find the right words for a few things while speaking. (And, of course, I'm not sleeping, which contributes to this.)

    I suggest we all follow the articles on Rituximab and keep discussing it. Dr. Jamie Deckoff-Jones' points are all very well-taken.

    I now have new worries about this drug after reading it, but it's all good … keeps the gray matter working and the thought process going about this topic and adds new insights.

    I really want to see what happens with a larger study which Norway is doing, and also what happens with very sick people, which they are going to study, too. (What I read is that it helps more with younger people and those who've more recently gotten sick.)

  20. >@Mark

    "Jamie, do you actually think there is only ONE cause of ME/CFS?"

    There were people like yourself that said the same about AIDS. However, doctors didn't get the opportunity to really mess with definitions in relation to that disease. There is ME, where some patients are put into the CFS bin, and then there is all the other reasons for fatigue, not that ME is fatigue. When using certain diagnostic tools, like CCC, the rates of Lymphoma jump dramatically from 0.05% to 5%. You don't have a reason to assume that ME is therefore NOT a disease with only one cause. It is a question to be answered through robust science.


  21. >I see all the time ME/CFS or CFS/ME. I think it's the same disease, just named differently in other countries, like Britain, perhaps others.

    And I have read that people with CFS have a higher rate than normal of a certain type of lymphoma.

    And the word "fatigue" is a mischaracterization. That is what one gets if one works too many hours or stays up with children and doesn't get enough sleep, a healthy person.

    This is bone-weary, painful deep exhaustion, where one cannot lift up one's arms to wash one's hair or walk to the grocery store or mail a letter, where one's muscles hurt horribly. It's where one can't walk up or down one's stairs or just barely, resting afterwards. It's so much more than even exhaustion. That doesn't even say it.

    If one doesn't have it or live with someone who does, it's very hard to understand it. My long-time friends don't even get it. Some think they do but they don't. One of them, a retired health care professional, doesn't get it at all, and I think it's because it wasn't in her textbooks years ago, and it doesn't fit anything she knows.

    This is so frustrating.

  22. >Hi Jamie

    Sorry, I unintentionally upset you. As Ann said I was I "merely pointing out that the clarity of a person's written communication wasn't necessarily a fair measure of how cognitively affected they are by ME." I was talking generally about how some of us will get by. ay if you are younger and you have parents who understand its helpful to have anything more than a comment proof read, if only because you are uncomfortable. First trips onto the internet can be a bit daunting. It's hard to get over the pain of doctors and various people saying "but you look fine".

    @Anon 9:28 PM

    Jamie doesn't owe anyone an apology. She has put up with so much unjustified abuse lately, and it is only a little misunderstanding.


  23. >Is there only one cause of multiple sclerosis Aids diabetes types 1 and 2

    yes there is

    why would anyone assume that there was more than one cause of the neuroimmune disease called ME

    The differing symptom presentation has a number of different explanation.The most esoteric being that the precise points of nucleotide insertions determine the symptom complex.The amount of mirochondrial damage determines the number of systems effected just like in any other mitochondrial disease.Thesymptom spectrum is not difficult to explain if one moves away from the fukuda fatigue and 4 minor symptoms BS

  24. >So the WPI has gone from "Thou shall worship the church!" to "They are damned heretics!". (That was fast)

    You religiously believe your model of an XMRV ("HGRV") infection is actually the reality. (Hint: No, it is just a model).

    Meanwhile Pope Mikovits preaches in lectures to the converted about mystical secret labs and mystical secret rituals to conjure up XMRV. Science is whatever Pope Mikovits says it is. Pope Mikovits is infallible. (For comparision, read what DeFreitas has said in "Osler's Web" looking back at her contribution to CFS research)

    And you accuse others of following a religion (which translates to "Godless infidel. Does not believe in XMRV"). Nice. Real nice.

  25. >@Tony Mach

    I think you will find that it is you who is religiously believing the opions of some researchers and not bothering to look at the data. VP62/XMRV has never once been found in nature, and the Lombardi viruses have been proven to not be VP62/XMRV, so why are you worshipping at the church of Coffin as if it ever was?

    If you understood PCR you would be aware that like any chemcial reaction, if you change the variables, you alter the outcome. It would be nice if you would start to acknowldge this fundamental scientific principle.

  26. >@ Tony Mach. Your lack of understanding of science and its methodology is truly astonishing

    all the negative studies have used assays which have not been optimised.Their clinical sensitivities were not established. There are two stages to optimising a new PCR assay.the first is to determine the theoretical limit of detection called the analytical sensitivity.Detecting a synthetic clone in a spiked sample is childs play.Expecting the same assay optimised to detect a artificial clone to detect a methylated provirus integrated into G-C rich DNA with complex secondary structures is simply childish

  27. >Emily,
    Yes, a misunderstanding. E communication lacks affect, so is easy to misinterpret. Thank you for identifying yourself.

    Thank you so much for the smile. I will try to remember…

    Tony Mach,
    Have you even read my stuff?

    Warm regards,

  28. >@ Tony Mach yes I have that is why its obvious that you don't know what you are talking about

  29. >A letter from Dr. Judy Mikovits to all ME/CFS patients, families and advocates

    Many of you have asked, "where is Dr. Judy Mikovits and what is she doing? Is she still doing research? Where can we go for testing?"

    Dr Judy Mikovits remains passionately committed to the patients and to a search for treatment and a better life for all of them.

    She refuses to compromise her integrity or the truth in a search for causes and treatment of disease. It is unfortunate, yet a sign of the society we live in, that politics and personal gain have interfered with science and the attempts of committed researchers to pursue the goal of scientific research.

    Dr Mikovits is pursuing opportunities with a variety of new research institutions and collaborations which show promise to continue in her research and to provide patients with new resources for diagnosis and treatment.

    She will make this information available on public sites for all patients to access and participate as they choose.

    Dr. Mikovits is no longer with the Whittemore Peterson Institute and has no role or responsibility for any of the activities of the Institute and never had any role in the clinical laboratory (VIPdx or Unevx)

    All patients or other individuals who wish to contact Dr. Mikovits may email via:

    Lilly Meehan at:


  30. >Dr DJ,

    I find your attempts to talk down and undermine the Rituximab data to be utterly bizarre. As a fellow patient, I've been giving you the benefit of the doubt despite some very irrational behaviour towards Jason in particular. Now I simply have no idea what your motives and agendas can possibly be. Same for your friend, Dr Snyderman. Talking down what is probably the best piece of treatment news ever published about this illness is frankly incredible behaviour. I will not be posting in future and leave you in the capable hands of Gerwyn, the non-virologist, who, on a daily basis, makes as much sense as this blog entry.
    Goodnight and good luck.

  31. >One theory I've been hearing is that the reason that Rituximab can work in CFS/ME is that herpes family viruses (e.g. EBV, HHV6) infect the B cells.

    Thus, it's posited, insofar as people have really active infections of these viruses, using a nuclear strike to wipe out the B cells can greatly reduce the infection and make people feel better temporarily.

    The idea that the herpes viruses can be responsible for a high percentage of the symptoms seems to be borne out by the reports by Stanford's Jose Montoya (and others) of occasional patients who have gotten to "mostly well" status as a result of Valcyte and other herpes antivirals. The problem with those drugs is that the die-off/IRIS is usually so severe that most people cannot take them without getting much sicker, in some cases permanently. The drugs also are quite toxic.

    Of course, no one has ever posited that the herpes viruses "cause" the illness. They're obviously downstream from the disastrously low NKC function, which itself is obviously downstream from something else. The only reasonable explanations that I've heard for this are a toxin or a retrovirus. (Not necessarily an MLV, based on the current state of the literature. Perhaps much more likely an endogenous retrovirus — which itself would be downstream from something else, with as far as I can tell the only reasonable suspect being toxicity.)

    I'm interested in this because my own core health improvements seem to have been far and away due to Valcyte and detox (including methylation support). The extreme avoidance now seems far less important to me as a short-term relief of symptoms (though that is welcome too) than as a leverage point to allow people to detox and kill pathogens. (Most CFS/ME patients are wholly unable to do either effectively, in an even slightly bad place.)

    The idea that the herpes viruses are (indirectly or directly) downstream from the toxicity component seems borne out by the fact that it's now been 10 months since I stopped the herpes antivirals and that I have experienced sharp gains during that time. (Everyone else with severe long-term CFS/ME appears to relapse quickly.)

    I'm now at the point where all my symptoms (except some mild morning tiredness and a little bit of irritability) are entirely gone, with very minimal avoidance of any sort (meaning just avoiding blatantly bad buildings and places like Incline Village).

    Thus, in my current conception of the illness, the Rituximab study is an intriguing clue that has the potential of allowing better understanding of the illness, rather than any sort of solution. (Wiping out B cells when we already have NKC problems does not seem to me optimal.)

    If I'm right and ALL of this is downstream from toxin (not just biotoxin) accumulations in our systems, then the real solution to the problem seems to be to get pharmaceutical companies to develop drugs to help us to detoxify more easily. The techniques available now are from the stone age, and what I've had to do to get the unexpectedly massive amounts of stored toxins in my systems out (it turned out to be unbelievable amounts!) is wholly impractical for most people. And had it not been for the two detox drugs that are available now (cholestyramine and Metafolin), I'd never have gotten anywhere.

    Thus, I am finding it increasingly frustrating that people studying this disease look at one little chunk (like the Rituximab improvements) without considering how it fits into the overall dynamic of the illness.

    I'd like to hear thoughts on whether my conceptions of why Rituximab worked for those few people seem to make sense.

    (P.S. Note that I am using "CFS/ME" here because Dan Peterson is currently doing so. I've never interacted with him, but I think he's gotten a really bad rap over the past months. I thus feel it a good thing to show my support for him.)


    Lisa Petrison, Ph.D.

    lisapetrison at yahoo

  32. >Anon 10:20 AM,

    My 'agenda' is to share my perspective as a patient and the mother of a patient, since many people have indicated that they find it helpful. Since I am also a doctor, and other doctors communicate freely with me, it should be all the more useful to you. In this case, doctor friends who have treated the complications of the drug, are pretty rabidly opposed. I do admit a definite bias against using drugs that can kill you for non-lethal conditions, especially before all gentle treatments have been explored, but evaluating risk is a personal decision, made in the context of one's own suffering. I'm sure some will try Rituxan, and we will learn from their trail blazing. Life is too short for each of us to try everything. We have members of our community trying arv's, GcMAF, Ampligen, antibiotics, stem cells, etc. Now some will try Rituxan. It is important that everyone communicate their experiences.


  33. >"I do think things will calm down a bit now naturally, since I don't foresee a great deal of retrovirology forthcoming on our behalf in the near future."

    Are you saying Mikovits has stopped doing RV research on CFS?

  34. >Anon 11:17 AM,

    Dr. Mikovits is trying to get situated to continue her work. If she started tomorrow, results would not be forthcoming any time soon, depending upon your definition of soon.


  35. >@Anon 10:20 AM

    That is what you are told to say. Try and focus on the scientific evidence and lets see why your interpretation is deviating from what is logical.


  36. >I see Rituximab as a brilliant and unexpected study that shows that CFS/ME is due to the body's continued inadequate response to ongoing infection. When the body cannot handle or eliminate infection, it often reacts with excess inflammation, cytokines, antibodies. It is aware the infection is there, but is not able to get it under control sufficiently (or because of genetics/molecular mimicry/HLA subtyptes, has a very loud inflammatory reaction to the infection from the get-go). The symptoms of the illness themselves are in large part due to the excess inflammatory chemicals, antibodies and toxins generated by the immune system in its inadequate response. This is true of much autoimmune disease.

    Aplastic anemia has been cured–yes, cured–with chemo. By wiping out and allowing the immune system to reboot, a deadly autoimmune disease where the body destroys its own red blood cells can be cured. What started the aberrant response? It could have been an infection. Sometimes the information loop that gets going has no ability to stop, and the body can't stop it on its own.

    It points the way to future "doorways" into treatment. Both GcMAF and Rituximab are geared toward the immune system itself, not to a specific pathogen. That should be noted.

    There may not be a specific pathogen. Probably not. That's what Peterson said in his interview. And it really does seem borne out by the varying epidemiology–the few notable outbreaks (Incline Village, Lynbrook) as well as lots of other stories–slow decline, vaccine-induced, tickbite-induced.

    Re: toxins, I'd rather we change our environment than develop drugs to deal with an environment we continue to poison. Reminds me of geoengineering to combat climate change, instead of shifting to clean power…no doubt toxins play a major role. Just saw studies in the last week on asthma ER visits tracking perfectly with pollution levels, even moderate pollution days…and diabetes, too…too much toxic assault impairs the immune response.

    Jill Neimark

  37. >I respect Dr. Snyderman's experience, and especially his willingness to put his life on the line for his opinions. I agree that Rituximab is unlikely to be a panacea, and B-cells are unlikely to be the only immune component affected by this disease. Still, I disagree with the negative evaluation he presents.

    We don't generally call something actual cancer until it begins the exponential growth which threatens life. Much of his experience in fighting cancer is like trying to stop a runaway freight train. ME/CFS is different.

    We have had far too much experience with medical professionals and diagnostic tests which fail to show any abnormality. (I'm not arguing that other criteria should not have been used, only that it was possible for even trained professionals to seize on measures which convinced them it was "all in our head".)

    We have immune impairment, but it seldom lands one of us in a hospital isolation unit. We have defects in aerobic metabolism, but these seldom prevent us from pushing ourselves, only punishing us with aftereffects. We have neurological problems, but even those of us who have had a seizure, as I have, do not regularly go on to develop epilepsy.

    Available evidence is that our bodies are putting up a struggle with this disease. At times the disease may even remit to such an extent we believe it gone.

    Considering the current state of ignorance about this specific pathology, the apparent success in two patients out of 15 experiencing long-term benefits with a very new treatment protocol is astounding, considering all the past failures.

    For those newly infected, this may offer the best hope we could ask for under current conditions. With experience, it should improve. What this work does not do is offer a "one size fits all" cure for ME/CFS. Patients, like Dr. Snyderman and myself, who have a long history of illness behind us, with complications, are less likely to respond as well. Treating physicians will need to be especially careful to "first, do no harm" in dealing with late-stage disease, and probably superinfections. You can't simply run treatment protocols like a "fire-and-forget" missile. It is appropriate to be cautious.

    However, I do feel like we have passed a subtle tipping point. We will all be learning for some time to come.

    Those who have seen my avatar will understand the special significance of my rule of thumb: "Hang On! This ride isn't over!"


  38. >Latest installment on origins of XMRV:

    "Characterization, Mapping and Distribution of the Two XMRV Parental Proviruses"

    Oya Cingöz, Tobias Paprotka, Krista A. Delviks-Frankenberry, Sheryl Wildt, Wei-Shau Hu, Vinay K. Pathak, and John M. Coffin

    JVI Accepts, published online ahead of print on 26 October 2011
    J. Virol. doi:10.1128/JVI.06022-11

    Follow-on to Paprotka et al. Science article. Better written (with primer combinations shown next to the gel bands this time, much easier to decipher).

    Coffin driving more nails into XMRV's coffin.

  39. >Coffins paper Paprotka et al. and this subsequent paper are flawed and missing data that was crucial to understanding why the papers are flawed. Paprotka et al. will be retracted for deliberately leaving out the use of a 3rd assay.

  40. >Jill —

    Oddly, showing that drugs can treat (however suboptimally) a disease seems perhaps to be the best way to get people to take that disease seriously. We've seen that with fibro (Lyrica) and now CFS/ME (Rituximab).

    Even if there were drugs that allowed people, pets and farm animals to detoxify wholly effectively, that wouldn't do anything for the bees and the bats and the frogs and other wildlife that (it seems) also are being killed off by toxins. And if we lose the bees, we're all dead.

    So fixing the environment is crucial.

    But maybe if drugs were developed to address toxicity, people would start to believe that environmental toxicity indeed is a problem and work to fix it. It's not like anything else environmentalists have tried so far has made much of a difference. :(

  41. >they still cant demonstrate that those assays could detect even synthetic XMRV if present and they still cant clone a whole erv( quaintly called pre xmrv1) in nu nu and hsd mice. They have still not screened any wild mice

    They still dont address the fact that the vp-62 sequence is synthetic and in no way connected to the real gammaretroviruses detected in people with ME

    VP-62 is joking xmrv and not the real version or versions

  42. >The heat is clearly on re the rituximab study people are being threatened with being banned by the administrators of ME/CFS forums if they dont toe the party line and think that the drug is the best thing since sliced bread

  43. >ok so an exogenous retrovirus found in cell lines and wild mice combines with an endogenous retrovirus which may exist in mice that might have been used to create the cell line 22rv1 which in itself contains an artificial retrovirus

    This artificial retroviral DNA sequence is then used as a positive control in assays looking for real retroviruses. When the assays cant detect real retroviruses then it must be because the real retrovirus does not exist

    It is little wonder that this lot decided that retroviral infection of humans was not possible and endogenous retroviruses could not possibly make up 8% of the human genome. With science like that they could never be wrong could they

  44. >I think Lisa has put forward a very reasonable explanation for the Mella & Flug study, and the viruses in question, EBV and CMV, are gamma viruses (has anybody noted that yet?).

    The problem with so many CFS/ME studies is the ignoring of prior research, all ALL the data must fit together, given the consistency in ME/CFS. The old EBV hypothesis does account for a lot of the data. For example, the sore throats, the lymphatic problems, heart and liver and spleen issues (all known issues with acute EBV). Then there is the dehydration in EBV (leading to OI and hypovolemia if chronic?), the known immune problems with EBV, and depletion of various cells including platelets. Finally, EBV is ordinarily managed by the NK cells, so B cell and NK cell pathologies are likely to be co-morbid to some extent in a chronic EBV pathology.

    There are often multiple hypothesis that will fit the data, but some fit better than others. This EBV-B cell hypothesis has a LOT of explanatory power. Worth some serious consideration.


  45. >Re: toxins. Even the environmentalists are largely living and working within the very polluted grid. Thats why they themselves don't understand, either. We need to raise John Muir and Aldo Leopold and maybe Thoreau from the dead to walk this world today and tell us how wrong it is (for us, and the species we bring down with us. Earth will be fine and a sixth mass extinction will nonetheless lead to another flowering of new life forms.)


  46. >Gerwyn @October 27, 2011 4:39 PM said…
    "ok so an exogenous retrovirus found in cell lines and wild mice combines with an endogenous retrovirus which may exist in mice that might have been used to create the cell line 22rv1 which in itself contains an artificial retrovirus" According to Paprotka and Coffin et al., two endogenous retroviruses present in mice recombined during xenografting to form a replication-competent retrovirion, unbeknownst to the researchers building the cell lines. Essentially XMRV is the result of an unplanned, unintentional marker rescue assay. The cell lines were passed around, and the recombinant replication-competent retrovirion contaminated several labs, including Dr. Silverman's. When Silverman detected the contaminating retrovirus, he naturally assumed that it was associated with samples from prostate cancer patients genetically predisposed for viremic infections, samples which were being analyzed to test for just such a hypothesis. The contaminating recombinant replication-competent retrovirion genome was isolated, cloned and sequenced, and he christened it XMRV. And the rest, as they say, is history….

    "This artificial retroviral DNA sequence is then used as a positive control in assays looking for real retroviruses. When the assays cant detect real retroviruses then it must be because the real retrovirus does not exist" In retrospective hindsight, yes, but at the time XMRV was thought to be a genuine retrovirus in the wild. Lombardi et al. detected it in samples from CFS patients. They were collaborating with Silverman. He sequenced what they detected. It matched up perfectly with known XMRV sequences. They were predisposed to accept its presence as fact, not artifact.

    "It is little wonder that this lot decided that retroviral infection of humans was not possible and endogenous retroviruses could not possibly make up 8% of the human genome. With science like that they could never be wrong could they" Endogenous human retroviruses are not the same thing as retroviral infection of, and proviral insertion into, somatic cells. Retroviral infection in humans is not being questioned here. It is XMRV and only XMRV that is being held up to scrutiny and failing inspection. I do not understand on the unnecessary and counterproductive insistence on any linkage between XMRV and possible human gamma retroviruses. XMRV can, and probably did, arise as Paprotka and Coffin hypothesize. XMRV as a complex artifact of cell line construction has nothing to do with any as yet undiscovered human gamma retroviruses that may or may not be out there.

Comments are closed.