A recent publication out of Germany (Hohn O. et al, Retrovirology, 2009 Oct 16;6(1):92. [Epub ahead of print] – PMID: 19835577) reports that prostate cancer patients with a known RNAse-L mutation, linked in the US to XMRV, had no evidence of XMRV infection. The same type of patient was shown to be associated with a high incidence of XMRV infection reported by the Cleveland Clinic in 2007.
I recently saw my longest follow-up stem cell patient at nine months out from stem cell treatment. This 57 yr old medically retired nurse was a KPS of 40 prior to stem cell therapy and an invalid with basic ADL assistance provided by her husband in the three months prior to stem cells given in early February 2009. She was essentially bed or couch bound and quite ill at times. Today, nine months later, I estimate her KPS at 65 as she notes she could now live alone and can engage in hobbies but could not at present work a regular part-time job.
It is my sense that infectious RV’s and possibly Herpes Group viruses are universal “test” agents for cells they infect to see if they can buffer their redox state in the case of either an externally induced redox shift to a more oxidizing environment or internally produced by the viruses themselves as they have the machinery to do it. If they can overwhelm the redox buffer, they replicate rapidly and kill the cells which lytically explode releasing virions to try again in other cells. If you cannot control the redox buffer systemically, you die because such loss of buffer threatens the DNA and the species with it. Therefore, these endogenous viruses are the wolves culling out the weak sheep in the flock of humans who in turn face external environmental challenges that threaten their redox balance. By this method, these endogenous viruses and especially RV’s direct human evolution to some unknown end but they only allow the subset of humans who can properly defend their redox state to survive or procreate.
As for other immune aberrations, they abound in CFS and the literature is full of them. CFS is an immune activation state involving both innate and cognate immunity and it is quite easy to show something immunologically abnormal in any of these patients. The problem is non-specificity of these immune aberrations and the fact that they come and go over time as these patients evolve and adapt immunologically. The co-infections and co-morbidities also make this a real immunologic nightmare for high-specificity correlations to XMRV. Perhaps someone will come up with an immune marker for XMRV that is both sensitive and specific now that it is in our sights. However, even low CD4 is not sensitive and specific to HIV infection. CD4 is more sensitive to HIV-AIDS evolution but even here there is not complete specificity as NIAID has a non-HIV AIDS clinic with low CD4 counts filled with CFS.
The possible presence of XMRV, especially if it resides in the brain which is very likely, could be activated by an immune activation state produced by immunotoxins such as VOC’s as well as influenza vaccines.
There are ways that retroviruses can impact the cell the I believe are especially important to CFS and data exists to support these assertions both in the literature (see below) and in such findings as low SOD and GPx in CFS and provides a mechanism to explain oxygen toxicity by ETM which is nearly universal in CFS.
As for overlap conditions in Dr. Mikovits’ cohort associated with CFS including FM and MCS and chronic Lyme and MS-like patients, I cannot speak to that. However, my clinic is filled with such overlap conditions. I suspect it will not matter very much. They are most likely infected with XMRV if they meet criteria for CFS with or without FM or MCS or chronic Lyme. Perhaps pure FM or pure MCS or pure Lyme will be different in degree of infection and maybe not. It will be very interesting to watch this data develop and expand to CFS-like conditions and the few pure FM and MCS cases that I have seen over the years. I have not really seen what I would call a pure Lyme case but many with CFS and a positive Igenex WB assay and antibiotic failure for chronic Lyme.
Proper buffering of the redox set point for the human body’s biological terrain is critical to control intracellular viral replication. Oxidative stess will potentially amplify XMRV replication. The biggest amplifier of oxidative stress due to any cause is NF Kappa B and one of the best inhibitors of NF-kB are the artemisins (Artesunate and Wormwood). Artemisins are also thought to be useful in cancer. We will be exploring the dose response curve for Artemisins to inhibit infectious XMRV in the near future to determine the best dose. We already know that activating NF-kB activates this virus and suppressing NF-kB inhibits XMRV. Artesunate is also known to inhibit HIV and all the associated herpes viruses that are co-factors in the evolution of AIDS and CFS as well.
The finding of antibody or active virus in 95% of CFS and 4% of controls is a result that argues for causality, in my opinion, especially with the associated RNAse-L corruption and NK functional impairment that might predict such an infection. This novel retrovirus could easily shift the redox state just like HIV as has been published in (2001) and (1995) and induce all manner of associated pathogens as seen in CFS. A redox shift could ultimately corrupt the gut ecology and create P450 decoupling based on NADPH depletion observed in CFS and lead to environmental illness as well. Time will tell but I think Dr. Mikovits is right to suspect causality. I also think this virus is infectious with at least ten million Americans infected who appear healthy and perhaps another four million Americans or more with CFS as recently estimated by the CDC (2007). However, disease expression may be more limited causing the illusion that it is not infectious. Furthermore, there may be other diseases that are similar and dissimilar to CFS that are associated with if not caused by XMRV.
The past week was chronic diarrhea week in my clinic which actually does not occur very often. Constipation is far more common than diarrhea in CFS. Below are details concerning two CFS patients with chronic diarrhea thoroughly worked up by the GI departments of two of the best institutions in our country which are getting almost nowhere, either with their diarrhea or their CFS. Both institutions are grasping at straws in both cases which is interesting.