Monday, 26 August 2013

An anti-viral for chronic fatigue syndrome?

The recent publication of the trial results by Jose Montoya and colleagues* looking at the possibility that the anti-viral drug valganciclovir (see here for some description) might provide clinical benefit for some patients diagnosed with chronic fatigue syndrome (CFS) is the source material for today's post. The ClinicalTrial.gov entry for the study is here.
Virology Founder @ Wikipedia 

Indeed, when reading the Wikipedia entry for how the valganciclovir - lets call it VGCV to save my poor typing hands - trial was long awaited on the back of some rather more preliminary observations (see here** and here***), one gets the idea that the recent Montoya paper might eventually turn out to be something pretty important. That being said, I'm going to turn to my old caveat on this blog about not providing medical or clinical advice.

The value-added on the recent trial was that it was methodological, a lot more comprehensive that the previous trial by the author: now being double-blind and placebo-controlled and following participants over a period of 6 months. The authors also used a suite of measures to ascertain physical and mental fatigue: the "Multidimensional Fatigue Inventory (MFI-20) and Fatigue Severity Scale (FSS)" alongside "monocyte and neutrophil counts and cytokine levels".

They found a few differences between VGCV and placebo in their group, some of them significant and some of them not so. Importantly - long quote coming up - "statistically significant differences in trajectories between groups were observed in MFI-20 mental fatigue subscore (P=0.039), FSS score (P=0.006), and cognitive function (P=0.025). VGCV patients experienced these improvements within the first 3 months and maintained that benefit over the remaining 9 months." Interesting too that among the biological results there were signs of a shift in immune function towards Th1 in the VGCV group (see here for a description) among other things.

OK, a couple of steps back first. This was a study based on quite a well-defined group of people with CFS who also presented with signs of an immune response (IgG antibodies) against human herpesvirus 6 (HHV-6) and Epstein-Barr virus (EBV). I understand that these viruses or rather exposure to these viruses have been discussed with CFS in mind previously (see here**** and here***** for example) outside of the historical viral reference (PVFS) although there still remains some 'discussion' about their role and relationship to CFS if and when detected.

To add to that viral - immune link, I note also that similar anti-viral preparations have also been examined with CFS in mind as per this study by Lerner and colleagues****** who used valaciclovir and even earlier this study******* using ganciclovir. Whilst methodologically sound, one might also reasonably expect that further research be undertaken following on from the Montoya and other results with a larger patient cohort.

I appreciate that to some, viral infections and CFS is still a little bit of a thorny issue in light of the quite recent XMRV story (see here for the drama) and even earlier some chatter about the use of transfer factor********. There is, therefore, always the possibility that the latest Montoya research might unfortunately suffer a sort of death by association as a consequence of any perceived link, despite the fact that as far as I can see they steered clear of anything murine leukemia virus-related virus in their work. Indeed as an aside, I should also point out the very interesting work being done on HERVs and myalgic encephalomyelitis (ME) which may or may not be relevant to the Montoya investigation too.

That also there is still some historical debate about the nature of CFS and the use of things like graded exercise and CBT as front-line treatment options (of which I am providing no opinion) is also another potential stumbling block to moving work like that of the Montoya paper out of the research domain and into something a little more accessible to specific patient groups. My view, as I've indicated in quite a few other posts on the subject of CFS, is that we are probably talking about a heterogeneous condition (possibly even a spectrum of conditions manifesting common symptoms. Sound familiar?) which appears to be multi-factorial in nature and pathology (see here and here and here for example). It's therefore highly likely that as Montoya and colleagues indicated "VGCV may have clinical benefit in a subset of CFS patients" as might other intervention options. The trick like Montoya has done, is to search out potential markers for what will work for who.

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* Montoya JG. et al. Randomized clinical trial to evaluate the efficacy and safety of valganciclovir in a subset of patients with chronic fatigue syndrome. J Med Virol. 2013 Aug 19. doi: 10.1002/jmv.23713.

** Watt T. et al. Response to valganciclovir in chronic fatigue syndrome patients with human herpesvirus 6 and Epstein-Barr virus IgG antibody titers. J Med Virol. 2012 Dec;84(12):1967-74. doi: 10.1002/jmv.23411.

*** Kogelnik AM. et al. Use of valganciclovir in patients with elevated antibody titers against Human Herpesvirus-6 (HHV-6) and Epstein-Barr Virus (EBV) who were experiencing central nervous system dysfunction including long-standing fatigue. J Clin Virol. 2006 Dec;37 Suppl 1:S33-8.

**** Burbelo PD. et al. No serological evidence for a role of HHV-6 infection in chronic fatigue syndrome. Am J Transl Res. 2012;4(4):443-51.

***** Lerner AM. et al. IgM serum antibodies to Epstein-Barr virus are uniquely present in a subset of patients with the chronic fatigue syndrome. In Vivo. 2004 Mar-Apr;18(2):101-6.

****** Lerner AM. et al. Valacyclovir treatment in Epstein-Barr virus subset chronic fatigue syndrome: thirty-six months follow-up. In Vivo. 2007 Sep-Oct;21(5):707-13.

******* Lerner AM. et al. A small, randomized, placebo-controlled trial of the use of antiviral therapy for patients with chronic fatigue syndrome. Clin Infect Dis. 2001 Jun 1;32(11):1657-8.

******** Ablashi DV. et al. Use of anti HHV-6 transfer factor for the treatment of two patients with chronic fatigue syndrome (CFS). Two case reports. Biotherapy. 1996;9(1-3):81-6.

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ResearchBlogging.org Montoya JG (2013). Randomized clinical trial to evaluate the efficacy and safety of valganciclovir in a subset of patients with chronic fatigue syndrome J Med Virol DOI: 10.1002/jmv.23713