Sunday, 26 June 2011

XMRV marks the spot?

In quite a few posts on this blog, the nature of the relationship between humans and the various smaller organisms which have populated our planet for many millions of years in one form or another, has been explored. Take for example the possible relationship between Toxoplasma gondii and schizophrenia covered in this post, and you can see that there is the potential for an interesting relationship between the human body, mind and various infective agents. The research of course does not say that we are all singularly at the mercy of such external organisms or that somehow free will is just an illusion; merely that our health and functioning might be influenced by lots of different factors, some of which we are only beginning to realise and understand.

My attention in this post is on an area of research which has been speculated to straddle quite a few conditions including autism and the various fatigue-related conditions. Readers might remember a post a few days back where I 'attempted' to look at some of the preliminary research commonalities between autism and chronic fatigue syndrome / myalgic encephalomyelitis (CFS/ME). If true, the focus of this post could be a very important commonality - if true.

Xenotropic Murine Leukemia Virus-Related Virus (XMRV) has had quite a bit of exposure in the research (and media) world of late. This retrovirus has been linked to quite a few different conditions, most notably prostate cancer, with some evidence presented for a possible association. I say linked, but be under no illusion that the evidence base is conclusive in this area. Indeed, with regards to prostate cancer, there have been several reports detailing no universal connection between XMRV and such cancer. One of the most recent studies from the CDC no less can be read here and details only a very low prevalence of XMRV in prostate cancer (1.9%). Of course that 1.9% is a reality for 1.9% of prostate cancers, but I think most people would admit that this is quite a small percentage of cases and is certainly not grounds for a universal relationship.

XMRV has perhaps found most controversy in its proposed relationship to CFS/ME. I don't really have the time or space to provide the full story linking the two conditions together so would perhaps refer you to this page for a summary. The paper which first suggested an association is this one published in Science, whereby XMRV was reported in PBMCs of people with CFS (67%) over and above controls (~4%).  The authors suggested that such a significant finding could either be indicative of an aetiological factor for CFS and/or could suggest potential 'treatment' options via the use of anti-retroviral drugs. CFS/ME is no stranger to a possible viral connection: ME has also been known as post-viral fatigue syndrome (PVFS) (not even mentioning the Royal Free incident of 1955). Indeed viral infections including glandular fever and even SARS have also been reported to be associated with symptoms. The subsequent research carried out on XMRV and CFS/ME has not however exactly provided a ringing endorsement for a possible connection between the two, despite some tentative confirmation of aspects related to the original findings. There are numerous papers suggesting no link between ME/CFS and XMRV including this one from the UK and this one from the USA. A good summary of the results so far is here. I am not going to say much more on the XMRV-CFS/ME relationship in this post aside from the fact that the controversy continues. There are various reasons to potentially account for the results obtained and there are many people better qualified than I to offer their informed opinion.

Autism spectrum conditions have also been discussed in connection with XMRV, at least preliminarily. I can't say for sure where and why XMRV was first related to autism but I seem to remember someone at the original study location, the Whittemore-Peterson Institute, suggesting that autism may also show some correlation based on other (unpublished) results. Viral infections accompanying autism have been the topic of some debate down the years with several suggestions put forward for a possible connection (see here and here). There have been some case reports detailing the diagnosis of XMRV infection in autism, but at this stage I cannot confirm whether the same issues potentially related to ME/CFS (i.e. cross-contamination) are applicable or not given the lack of information on testing protocols. The limited published group evidence on any connection between autism and XMRV is pretty categorical: no presence of XMRV in cases of autism (see here and here). As per the mantra of this blog, science is about probabilities not absolutes. In the case of XMRV and autism, I have to say that the data (so far) is quite explicit in the direction of its findings.

The initial interest in XMRV has perhaps abated slightly given the number of studies that have been completed. I think there are a few interesting points to note from this whole issue including the concept of universality (and what it means when potentially assigning a correlate to all or a large proportion of people with often nebulous symptoms), correlation and causation (one does not equal the other - even in those cases where XMRV has been detected, the various data do not yet provide any indication that treating XMRV actually impacts on presented symptoms outside of just reducing viral load) and population differences. Because of the small number of trials specifically looking at autism spectrum conditions, I would perhaps like to see some further data on XMRV and whether issues such as age, geographic population, sub-diagnosis and co-morbidity show any potential effects before drawing a line under the XMRV story and the question of whether XMRV really does mark the spot.