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Inflammation and autoimmunity: risk assessment and predictive approaches through the analytical armamentarium

Marshall, T.G. (2011) Inflammation and autoimmunity: risk assessment and predictive approaches through the analytical armamentarium. The EPMA Journal, 2 (S1). pp. 167-171.

Link to Published Version: http://dx.doi.org/10.1007/s13167-011-0116-8
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Abstract

The absence of a clear understanding of human chronic-disease, especially the absence of a clear pathogenesis, has hindered implementation of targeted predictive and preventive medicine. But the emerging sciences of metagenomics and proteomics have now clarified a mechanism whereby not just one or two discrete pathogens can drive the disease process, but where a very large number of viral, fungal and bacterial species, accumulating in the human body over the course of a lifetime, progressively weaken the human innate immune system. Homo sapiens is not a sterile compartment, but a super-organism harboring thousands of species of microbes in its cells and tissues. Those microbes which have evolved to persist inside nucleated and phagocytic cells can engender both genomic and proteomic interference within the host cell metabolism, precipitating the disease processes. Key components of this microbiota persist by reducing expression of, and by, the VDR Nuclear Receptor, which is at the heart of the human innate immune system. Only in Homo sapiens is the VDR responsible for expression of Cathelicidin, TLR2, TACO and a number of other endogenous anti-microbials. Animals have different antimicrobial defenses, and thus cannot properly model human chronic disease. Pathogens already known to persist by dysregulating the human VDR include EBV, Mycobacteria, Borrelia, Aspergillus and HIV. Antimicrobial therapy is difficult, as the diseased VDR cannot be simply restored by endogenous metabolic processes, as it can in healthy individuals. Nor can antibiotics function in-vivo in the absence of a competent innate immune system. We have shown that the drug Olmesartan can be retargeted to function as a VDR agonist, allowing innate immunity to recognize the pathogens, and reverse the disease process. Recovery is very slow, as care must be exercised to ensure the resulting cytokine-storm does not become life-threatening. Over the last decade, we have implemented a worldwide clinical collaboration to demonstrate ‘proof of concept’ efficacy in hundreds of subjects with serious chronic disorders, ranging from schizophrenia and manic depression, through ALS and MS, to sarcoidosis and arthritis. It seems certain that the current epidemic of chronic disease can not only be controlled, it can be reversed by implementation of preventative measures aimed at minimizing the accumulation of pathogenic organisms into the human microbiome.

Publication Type: Journal Article
Murdoch Affiliation: School of Veterinary and Biomedical Sciences
Publisher: Springer
URI: http://researchrepository.murdoch.edu.au/id/eprint/10113
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