As expected, the XMRV virus research has stimulated interest in a host of studies to see if the initial study results can be replicated and to discover therapies for XMRV. Since our December 4, 2009 newsletter on XMRV testing, two interesting new studies have been reported.
The first study suggests that of the 10 most common antivirals used against retroviruses, the only one that showed any effectiveness against XMRV (in test tubes) was AZT. This will give researchers an important starting point in exploring therapy for XMRV. I would NOT recommend this therapy yet for CFS though, as it can be fairly toxic and we don’t know if it will have any benefit.
The second study was done in the UK, and screened 186 CFS patients for XMRV using PCR testing (looking for genetic material). None of these patients tested positive for XMRV. This finding should be tempered by the same issue being found for prostate cancer and XMRV. Where the American studies found XMRV to be more common in prostate cancer, this association was not found in other European studies. This suggests that either XMRV infection is more of an issue in the US or that the testing methodology used in the European study was inadequate (which is what the WPI is claiming).
As a medical reporter who has been closely involved in the CFS & fibromyalgia field as a patient, physician and researcher for over 30 years, I find both the science and politics to be fascinating. You will hear some hard hitting attacks (sometimes done subtly, sometimes not so subtly) coming from both sides. And I suspect the melee has just begun.
In the following we will present the two above studies in more depth. In addition, we’ll look at the rebuttal of the UK findings by the WPI (which did the initial study) and some background on a few of the new study authors — significant, as one of them seems determined to have CFS be addressed as a psychological problem!
What Do the Two New Studies Show?
The first study used test tube experiments to see which antivirals might be effective against XMRV. The researchers took the 10 most common AIDS drugs (AIDS and the XMRV virus are both retroviruses) and tested their effectiveness against XMRV. I found that I was holding my breath while waiting to get the answer to the question of what might work against XMRV. The results?
Of the 10 antivirals, the only one that showed any effectiveness against XMRV was an old antiviral called AZT ("Retrovir" being the brand name and the generic name being "zidovudine"). This medication has been around long enough that it is no longer under patent protection. This has the benefit of making the medication less expensive but also has the downside of making it less attractive for drug companies to spend research dollars on.
I would not recommend trying this medication at this time. Although it may become worth using if shown to be effective in chronic fatigue syndrome, without evidence of its effectiveness for this disease the medication is too toxic. To give you an idea of the concerns, here's the FDA-required black box warning in the Physician's Desk Reference under AZT (Retrovir/zidovudine):
Retrovir (zidovudine) has been associated with hematologic toxicity including neutropenia and severe anemia particularly in patients with advanced human immunodeficiency virus (HIV) disease.
Prolonged use of Retrovir has been associated with symptomatic myopathy.
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogues alone or in combination, including Retrovir and other antiretrovirals.
To put it in perspective though, AZT has been used safely in an enormous number of AIDS patients.
The bottom line? Although it may be helpful, and I consider this research study to be very important as a first step, I would not recommend being the first CFS patient on your block to try it. I would wait and let other people volunteer to be the guinea pigs. If we find that many people report it to be helpful, we will move this discussion to the next level.
What Does the Second Study Show?
Basically, as noted above, it performed PCR testing on 186 people in England suffering with CFS and found that none of them was positive for the XMRV virus. So how does one make sense of this conflicting information?
There are several probable answers to what is occurring:
It could simply be that the testing methods used in the second study were not reliable. This is the impression of the folks at the WPI, where the initial study was done, and in a press release the WPI comments on the new study.
This is not an unlikely scenario, as testing done at the WPI was much more complex and I suspect more likely to be accurate.
XMRV virus may simply be more common in humans in the United States and rare in Europe. This was supported by the four studies done on XMRV and prostate cancer.
Questions have been raised about the patients used in both studies.
One of the main researchers in the England study is Dr. Simon Wessely, a nice and very bright fellow who I suspect is so blinded by his determination to have CFS viewed as a psychological disease requiring only counseling that I find most of his research to have a decidedly unhealthy bias. I think if he applied his same bias to patients dying of lung cancer, he would also see them as being “not really sick” (i.e., he would see them as crazy). On the other hand, I have enjoyed the work of Anthony Cleare on HPA axis/adrenal issues in CFS over the years. I find it interesting that they have teamed up on a number of studies recently — including this one.
The source of the WPI study patients, based on the paper, is also not clear to me. My main concern is that they not come largely from a single epidemic of CFS, such as the Tahoe group, as this could largely skew the results. Again, we look forward to seeing the results of testing of patients from around the country (and indeed around the world) to see what percentage are positive. Interestingly, rumor has it that the WPI has already run over 300 mailed in samples, with about 1/3 of them being positive, including some from the UK.
For those setting up studies looking for XMRV in CFS patients, the above study suggests a simple way to answer these questions if they arise again. As a medical reviewer, it would be very helpful if the studies sent all or even 10-20% of their blood samples to the WPI for testing, while also doing the testing in their own labs. Half of the samples sent to the WPI should be from healthy patients, and the samples should be blinded (i.e., not labeled as to whether they are coming from CFS or healthy control patients). If the samples sent to the WPI clearly again come up positive for CFS and negative for healthy patients, as in the earlier study, it would immediately answer the question of whether there is a methodology problem and it would quickly answer many of our questions. So in real life, there is really a very simple approach that could answer these questions.
In the mean time, I suspect the debate will continue to heat up. Stay tuned!