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Helminth Therapy: Advances in the use of Parasitic Worms Against Inflammatory Bowel Diseases and its Challenges.

ABSTRACT: Development of modern medicine and better living conditions in the 20th century helped in reducing a number of cases of infectious diseases. During the same time, expansion of autoimmunological disorders was noticed. Among other are Inflammatory Bowel Diseases (IBD) including ulcerative colitis and Crohn's disease which are chronic and relapsing inflammation of the gastrointestinal tract. Absence of effective treatment in standard therapies effects the search for alternative opportunities. As per hygienic hypothesis increasing number of cases of autoimmune diseases is as a result of reduced exposure to pathogens, especially parasites. Thus, one of the promising remedial acts against IBD and other allergic and autoimmune disorders is "helminth therapy". Cure with helminths seems to be the most effective therapy of IBD currently proposed. Helminth therapy focuses on advantageous results that have been obtained from the clinical trials, but its mechanisms are still unclear. Explanation of this phenomenon would help to develop new drugs against IBD based on helminth immunomodulatory molecules.

SUBMITTER: Maruszewska-Cheruiyot M

PROVIDER: S-EPMC6799527 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Helminth Therapy: Advances in the use of Parasitic Worms Against Inflammatory Bowel Diseases and its Challenges.

Maruszewska-Cheruiyot M M Donskow-Łysoniewska K K Doligalska M M

Helminthologia 20180127 1

Development of modern medicine and better living conditions in the 20th century helped in reducing a number of cases of infectious diseases. During the same time, expansion of autoimmunological disorders was noticed. Among other are Inflammatory Bowel Diseases (IBD) including ulcerative colitis and Crohn's disease which are chronic and relapsing inflammation of the gastrointestinal tract. Absence of effective treatment in standard therapies effects the search for alternative opportunities. As pe ...[more]

PMID: 31662622

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Project description:To improve quality of life and prevent long-term risks in patients with inflammatory bowel diseases (IBDs: Crohn's disease, ulcerative colitis), it is essential to suppress inflammatory activity adequately. However, corticosteroids are only suitable for therapy of acute flares and the evidence for positive effects of immunosuppressive substances like azathioprine or 6-mercapropurine is mainly limited to maintenance of remission. In addition, only subgroups of patients benefit from biologicals targeting tumour necrosis factor α or α4β7 integrins. In summary, until now the disease activity is not sufficiently controlled in a relevant fraction of the patients with IBD. Thus, there is an urge for the development of new substances in the therapy of ulcerative colitis and Crohn's disease. Fortunately, new oral and parenteral substances are in the pipeline. This review will focus on oral substances, which have already passed phase II studies successfully at this stage. In this article, we summarize data regarding AJM300, phosphatidylcholine (LT-02), mongersen, ozanimod, filgotinib and tofacitinib. AJM300 and ozanimod were tested in patients with ulcerative colitis and target lymphocyte trafficking through inhibition of the α subunit of integrin, respectively binding to the sphingosine-1-phosphate receptor (subtypes 1 and 5) on lymphocytes. Mongersen was utilized in patients with Crohn's disease and accelerates the degradation of SMAD7 mRNA, which consequently strengthens the mainly anti-inflammatory signalling pathway of transforming growth factor β1. Various Janus kinase (JAK) inhibitors were developed, which inhibit the intracellular signalling pathway of cytokines. For example, the JAK1 blocker filgotinib was tested in Crohn's disease, whereas the JAK1/3 inhibitor tofacitinib was tested in clinical trials for both Crohn's disease and ulcerative colitis. A different therapeutic approach is the substitution of phosphatidylcholine (LT-02), which might recover the colonic mucus. Taken together, clinical trials with these new agents have opened avenues for further clinical studies and it can be expected that at least some of these agents will be finally approved for clinical therapy.

Project description:BackgroundThe novel coronavirus SARS-CoV-2 causing COVID-19 disease is yielding a global outbreak with severe threats to public health. In this paper, we aimed at reviewing the current knowledge about COVID-19 infectious risk status in inflammatory bowel disease (IBD) patients requiring immunosuppressive medication. We also focused on several molecular insights that could explain why IBD patients appear not to have higher risks of infection and worse outcomes in COVID-19 than the general population in an attempt to provide scientific support for safer decisions in IBD patient care.MethodsPubMed electronic database was interrogated for relevant articles involving data about common molecular pathways and shared treatment strategies between SARS-CoV-2, SARS-CoV-1, MERS-CoV, and inflammatory bowel diseases. Besides, Neural Covidex, an artificial intelligence tool, was used to answer queries about pathogenic coronaviruses and possible IBD interactions using the COVID-19 Open Research Dataset (CORD-19). Discussions. Few molecular and therapeutic interactions between IBD and pathogenic coronaviruses were explored. First, we showed how the activity of soluble angiotensin-converting enzyme 2, CD209L other receptors, and phosphorylated ? subunit of eukaryotic translation initiation factor 2 might exert protective impact in IBD in case of coronavirus infection. Second, IBD medication was discussed in the context of possible beneficial effects on COVID-19 pathogeny, including "cytokine storm" prevention and treatment, immunomodulation, interferon signaling blocking, and viral endocytosis inhibition.ConclusionsUsing the current understanding of SARS-CoV-2 as well as other pathogenic coronaviruses immunopathology, we showed why IBD patients should not be considered at an increased risk of infection or more severe outcomes. Whether our findings are entirely applicable to the pathogenesis, disease susceptibility, and treatment management of SARS-CoV-2 infection in IBD must be further explored.

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Helminth Therapy: Advances in the use of Parasitic Worms Against Inflammatory Bowel Diseases and its Challenges.

Publications

Helminth Therapy: Advances in the use of Parasitic Worms Against Inflammatory Bowel Diseases and its Challenges.

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