Novel Therapeutics for Multiple Sclerosis Designed by Parasitic Worms

Dixit, Aakanksha; Tanaka, Akane; Greer, J. M.; Donnelly, Sheila

doi:10.3390/ijms18102141

Cited by 24 publications

(25 citation statements)

References 93 publications

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“…Further evidence supporting this theory comes from studies of other pathogens that are normally acquired in childhood in poor hygiene environments such as Helicobacter pylori [134] and parasites such as Toxoplasma gondii [135] and Trichuris trichuria exposure, which also displays a negative association with MS. Though in the case of helminth parasites, there may also be direct immunosuppressive effects of excretory proteins from the worms that are being explored as potential MS therapies [136].…”

Section: Environmental Risk Factors For Msmentioning

confidence: 99%

The Interaction between Viral and Environmental Risk Factors in the Pathogenesis of Multiple Sclerosis

Tarlinton

Хайбуллин²,

Гранатов³

et al. 2019

IJMS

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Multiple sclerosis (MS) is a chronic debilitating inflammatory disease of unknown ethology targeting the central nervous system (CNS). MS has a polysymptomatic onset and is usually first diagnosed between the ages of 20–40 years. The pathology of the disease is characterized by immune mediated demyelination in the CNS. Although there is no clinical finding unique to MS, characteristic symptoms include sensory symptoms visual and motor impairment. No definitive trigger for the development of MS has been identified but large-scale population studies have described several epidemiological risk factors for the disease. This list is a confusing one including latitude, vitamin D (vitD) levels, genetics, infection with Epstein Barr Virus (EBV) and endogenous retrovirus (ERV) reactivation. This review will look at the evidence for each of these and the potential links between these disparate risk factors and the known molecular disease pathogenesis to describe potential hypotheses for the triggering of MS pathology.

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Section: Environmental Risk Factors For Msmentioning

confidence: 99%

The Interaction between Viral and Environmental Risk Factors in the Pathogenesis of Multiple Sclerosis

Tarlinton

Хайбуллин²,

Гранатов³

et al. 2019

IJMS

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“…TLRs 3 and 6 activate TRIF and therefore cellular (Th1) immunity; TLRs 1,2,4,5,7,8,9 and 11 activate MyD88 and therefore antibody-mediated (Th2) immunity (Mohammad Hosseini, et al, 2015). The essential role of innate immunity in the development and ongoing support of AD pathogenesis is further demonstrated by the effectiveness of anti-TLR ligands as AD treatments (Barrat & Coffman, 2008;Peón, et al, 2017;Dixit, et al, 2017).…”

Section: Act Explains How Innate Activation Is Required For Ad Initiamentioning

confidence: 99%

<strong>A General Theory of Autoimmune Disease Causation: Integrating Innate and Adaptive Immunity, Altered Antigen Processing, Sex and Genetic Predispositions, and Microbiome Effects</strong>

Root‐Bernstein¹

2019

Preprint

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Current theories of autoimmunity are diverse, sometimes contradictory, and suffer from incompleteness. Although substantial evidence exists that adaptive and innate immunity, sex, genetic predisposition, and the microbiome all play essential roles in autoimmune disease etiologies and pathogenesis, and that antigen processing is altered during disease induction, no existing theory integrates all of these factors through a single, coherent mechanism. In an attempt to focus the field on the need to elucidate such an integrative mechanism, I propose one possibility here that, if nothing else, helps to identify the nature of the problems that need to be addressed. My theory is that autoimmune diseases are induced by normal immunological responses to unique pairs of complementary antigens, at least one of which is a molecular mimic of a host target.  Each antigen in the complementary pair induces a complementary immune response (T or B cell); although each immune response is idiotypic in origin, the antigenic complementarity results in what appears to be an idiotype-anti-idiotype relationship between the responses. Additionally, because of the antigenic complementarity, each immune response mimics one of antigens, abrogating the distinction between self and non-self. If at least one of the antigens mimics a host antigen, then the resulting immunological civil war spreads to a host tissue. Complementary antigens also alter antigen processing so that antigens that would normally be proteolytically digested are presented by the major histocompatibility complex (MHC) to T and B cell receptors inducing a cross-reactive immune response. The resulting civil war is supported by the innate immune system due to the complementarity of the initiating antigens.. Complementary antigens stimulate synergistic toll-like receptors (TLR) and/or nucleotide-binding oligomerization receptors (NOD) resulting in up-regulation of cytokine production and further stimulation of the adaptive immune response. Because the immune responses (e.g., antibodies) mimic the initiating antigens, this synergistic activation of innate immunity becomes chronic. Additionally, TLR and NOD function are highly sensitive to sex hormones, some becoming up-regulated and some down-regulated in the presence of either testosterone or estrogens. This sensitivity explains how sex modifies susceptibility to autoimmune diseases. Genetic mutations in TLR, NOD and MHC further alter antigen presentation and the degree to which antigens stimulate an immune response explaining how genetics also modifies susceptibility. Finally, sex hormones also alter the host microbiome, which in turn modulates autoimmune disease risk by shaping the immunological nature of self and by mediating susceptibility to microbial infection.  Moreover, it appears that the microbiome camouflages itself from the immune system by mimicking the host antigenic repertoire; the mimicry between the antigens of the microbiome and the host results in selective attacks on microbiome constituents concomitant with any autoimmune attack on host tissues. This antigenic complementarity theory thereby integrates all major elements known to affect, or be affected by, autoimmune diseases and provides a set of testable implications.

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“…For example, there are ongoing trials with fecal microbial transplantation (FMT) [133][134][135]. Therapeutical infestation with helminths has been also explored, because parasites are been known to skew immune response towards Th2 subtype, thus in effect ameliorating neuroinflammation [136][137][138].…”

Section: Gut Microbiome Modificationmentioning

confidence: 99%

Multiple sclerosis - new therapeutic directions

Łowiec¹,

Trzonkowski²,

Chwojnicki³

2017

Eur J Trans Clin Med

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Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative disease which affects the central nervous system. Currently, there are numerous disease-modifying therapies for this condition. Most of them address the inflammatory aspects of the disease and are most effective in the relapsing-remitting stages of multiple sclerosis. However, none of them can completely stop the progression of MS and they are usually associated with adverse effects. There is an ongoing search for novel approaches that involve different modes of action. Here, we discuss examples of new immunomodulating agents such as antigen-specific therapies, neuroprotectants, regenerative strategies and gut microbiota modification.

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Novel Therapeutics for Multiple Sclerosis Designed by Parasitic Worms

Cited by 24 publications

References 93 publications

The Interaction between Viral and Environmental Risk Factors in the Pathogenesis of Multiple Sclerosis

The Interaction between Viral and Environmental Risk Factors in the Pathogenesis of Multiple Sclerosis

<strong>A General Theory of Autoimmune Disease Causation: Integrating Innate and Adaptive Immunity, Altered Antigen Processing, Sex and Genetic Predispositions, and Microbiome Effects</strong>

Multiple sclerosis - new therapeutic directions

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