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Stealth Adapted Viruses and the Alternative Cellular Energy (ACE) Pathway in Alzheimer’s Disease W. John Martin, M.D., PhD. Institute of Progressive Medicine, South Pasadena CA 91030 USA Abstract While some investigators have suggested a possible infectious origin of Alzheimer’s disease, it is usually argued that the actions of the virus must be indirect and quite possibly delayed. For example, common infections occurring in pregnancy can lead to elevated cytokine levels that may affect fetal brain development, with potential later life consequences. Certain infectious agents might trigger the production of antibodies that cross-react with neuronal components, thereby interfering with normal brain function. Such self-reacting antibodies may continue to form as part of an ongoing autoimmune process. None of these scenarios envisions viruses as the direct cause of ongoing cell damage. Still there are persisting hypotheses that viruses may be directly contributing to Alzheimer’s disease. Most attention has been paid to herpes simplex virus (HSV) and is based on the following observations: i) HSV infected fibroblasts secrete both β-amyloid and tau-proteins. These markers may be a consequence of virus damage to neuronal cells. Delayed elimination of these products from infected brains may be age-related. ii) Budding herpes viruses directly interact with amyloid precursor protein, affecting its normal transport and distribution iii) HSV DNA is detected in association with the amyloid plaques and also with the neurofibrillary tangles that mostly comprise phosphorylated tau proteins. iv) Alzheimer’s disease plaques and tangles also contain complement factors and HSV binding cellular proteins. v) The distribution of the Alzheimer’s disease markers progressively involves increasing areas of the brain; consistent with a spreading infectious process. vi) Many of the gene alleles shown to significantly enhance susceptibility to Alzheimer’s disease, e.g. ApoE-e4, also promote the infectivity of cells by HSV. vii) Anti-HSV antibody levels, including IgM, increase in conjunction with the onset of Alzheimer’s disease; yet the avidity (binding capacity) of anti-HSV antibody is lower in those with severe disease, consistent with reduced antibody protection. viii) Suggestive clinical improvements have occurred in Alzheimer’s disease patients receiving therapies that could potentially inhibit HSV. Examples include intravenous gamma globulin and statins. Data also exist for the active involvement of other herpes viruses in Alzheimer’s disease. Moreover, caregivers and family members of Alzheimer’s patients may become ill with “burnout” syndrome. Altogether, the findings are consistent with the presence of stealth adapted viruses. Background: A role for virus infection in the pathogenesis of Alzheimer’s disease has largely been dismissed due to the lack of an accompanying inflammatory reaction. Relatively few components in viruses are actually targeted by the cellular immune system. Deletion or mutation of these components can yield derivative viruses; which can cause cellular damage, yet are not effectively recognized by cytotoxic T lymphocytes. This generic immune evasion mechanism is termed “stealth adaptation” and can potentially occur with all human and animal viruses. As confirmed in animal inoculation studies, the brain is particularly susceptible to symptomatic illness cause by localized stealth adapted virus infection. Methods: Tissue culture evidence for stealth adapted virus infection was sought in patients with various neuropsychiatric illnesses. The basic technique involves co- culturing patients’ mononuclear cells with indicator human fibroblasts and observing for the formation of foamy, vacuolated cells with syncytia; the characteristic cytopathic effect (CPE) caused by stealth adapted viruses. Results: Positive cultures were consistently observed in patients with neuropsychiatric illnesses, including patients clinically diagnosed with Alzheimer’s dementia. Approximately, 10% of control cultures yield positive results. Both conventional and stealth adapted viruses can be suppressed by a non- immunological defense mechanism involving the alternative cellular energy (ACE) pathway. For example, local activation of the ACE pathway using neutral red dye plus ultraviolet light expedites the healing of HSV skin lesions (Martin WJ, Stoneburner S. Exp. Mol. Path. 78:131-134,2005). Promising results have also been obtained by enhancing the ACE pathway in children with autism (Martin WJ. J Alzheimers Dis. Parkinsonism 3:4,2013). Beyond its role in suppression of virus infections, an enhanced ACE pathway can potentially compensate for deficiencies in the supply of oxygen, blood and/or nutrients required for normal mitochondria mediated cellular metabolism. Current approaches to monitoring and enhancing the ACE pathway will be described, including the value of consuming energized fluids and ingestion of enerceutical™ foods. Conclusions: Studies are urgently needed to monitor the potential benefits of enhancing the ACE pathway in Alzheimer’s disease patients. If successful, these studies can be followed by efforts at preventing or at least delaying the onset of Alzheimer’s disease and other neuropsychiatric illnesses. Virus evasion of cellular immune recognition via deletion/mutation of relatively few antigens normally targeted by CD8 T lymphocytes Consequently, these derivative viruses do not evoke an inflammatory response Stealth adaptation can potentially occur with all human and animal viruses Additional deletions/mutations are common and can greatly expand the host range of stealth adapted viruses Heterogeneity limits the diagnostic value of molecular detection methods Foamy, vacuolated cells are inducible in tissue cultures using specialized virus culture techniques. Infected cells often show syncytia Examples include derivatives of African green monkey simian cytomegalovirus (SCMV). Polio vaccines are produced in cultures of SCMV infected monkeys The brain is particularly susceptible to symptomatic stealth adapted virus illnesses Positive cultures in vast majority of tested neuropsychiatric patients, compared to generally weaker positive cultures in ~ 10% controls blood samples Animal inoculation studies demonstrate acute illness followed by clinical recovery in the absence of inflammation Recovery also occurs in infrequently fed virus cultures; due to the production of pigmented, particulate materials with energy transducing properties Infected cells in cultures & brain biopsies survive in spite of disrupted mitochondria Particulate materials replace the need for metabolism of food and comprise an alternative cellular energy (ACE) pathway. ACE pigments can also have rather remarkable lipid synthesizing activity, as shown in long-held acellular cultures containing these pigments ACE pathway operates, at least in part, through an inducible dynamic (kinetic) property of fluids, including water Water activation occurs via absorption of an environmental force termed KELEA™ for kinetic energy limiting electrostatic attraction There are various therapeutic option of enhancing the ACE pathway 1. Ultraviolet (UV) light activation of ACE pigments produced in herpes simplex virus (HSV), herpes zoster virus (HZV) & human papillomavirus (HPV) lesions. Reaction is triggered by applying neutral red dye to the UV illuminated lesions. 2. Healing occurs in both treated lesions and in more distant lesions on which the dye is not necessarily applied. Recurrences reduced as shown with Dr. Jon Stoneburner. 3. This approach is also suitable for treating herpes infected patients between recurrences and also for alleviating post herpetic neuralgia. 4. Rather than relying upon initiating the phototherapy with the body's ACE pigments, the reaction can be triggered using solutions of neutral red dye in activated water and other fluids; placed in close proximity to active lesions or to sites of prior recurrences. 5. Protocol shown to successfully to activate the ACE pathway in autistic children 6. Injections of an activated water product, developed as a homeopathic formulation, was shown in collaborative studies to be effective in treating children with diarrhea and in more recent studies by others, to suppress tuberculosis and reduce HIV levels in AIDS patients. 7. There are multiple ways of activating water, resulting in varying degrees of kinetic activity being imparted to the water. 8. Certain foods, termed enerceuticals™, e.g. moringa oleifera, have low levels of water activating activities, as do some dietary supplements. 9. Various external energy delivering devices also have water activating activity. 10. In addition to human studies, multiple applications of activated water exists in agriculture and industry. 11. For information regarding clinical trials, contact [email protected] (626-616-2868) Herpes Viruses in Alzheimer’s Stealth Viruses & ACE Pathway Enhancing the ACE Pathway
