Abstract
Chronic fatigue syndrome (CFS)/myalgic encephalomyelitis (ME) has long been associated with the presence of infectious agents, but no single pathogen has been reliably identified in all patients with the disease.
Recent studies using metagenomic techniques have demonstrated the presence of thousands of microbes in the human body that were previously undetected and unknown to science. More importantly, such species interact together by sharing genes and genetic function within communities.
It follows that searching for a singular pathogen may greatly underestimate the microbial complexity potentially driving a complex disease like CFS/ME. Intracellular microbes alter the expression of human genes in order to facilitate their survival.
We have put forth a model describing how multiple species-bacterial, viral, and fungal- can cumulatively dysregulate expression by the VDR nuclear receptor in order to survive and thus drive a disease process.
Based on this model, we have developed an immunostimulatory therapy that is showing promise inducing both subjective and objective improvement in patients suffering from CFS/ME.
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Paradoxically, immunosuppressive therapies often result in short-term symptom improvement or resolution by decreasing the cytokine, antibody and endotoxin release associated with an inflammatory response towards acquired pathogens. This temporary symptom improvement should not be mistaken for actual reversal of the disease process. The monoclonal antibody rituximab, which has recently been used to deplete the B cells of patients with CFS/ME[4], may be an example of a therapy that elicits “improvement” in this fashion. It’s instructive to note that the apparent
progress noted among CFS/ME patients taking the medication is almost always followed by profound relapse. Furthermore, the use of rituximab has been linked to the resurgence of latent infections including hepatitis B reactivation, multifocal leukoencephalopathy, and Pneumocystis pneumonia [93].
Subsequently, over the last decade, our group has developed a novel therapy that seeks to stimulate rather than suppress the innate immune system [94]. Instead of slowing the immune response, we aim to directly target microbes by stimulating immune defenses. Central to the treatment is the use of olmesartan medoxomil. While this drug was approved as an angiotensin II receptor agonist (ARB), we showed that it also has a high affinity for the VDR nuclear receptor,for which it is most likely a partial agonist [95].
In a VDR- compromised individual, olmesar tan medoxomil stimulates the expression of the many endogenous antimicrobials under VDR control, and helps to gradually restore the activity of other nuclear receptors, which may have been impacted by VDR dysregulation.
Immunostimulation in the treatment for chronic fatigue syndrome/myalgic encephalomyelitis by AD Proal et al in Immunologic Research, 11 April 2013
