The parasitic worm-derived immunomodulator, ES-62 and its drug-like small molecule analogues exhibit therapeutic potential in a model of chronic asthma

Scientific Reports
Jennifer C ColtherdMargaret M Harnett

Abstract

Chronic asthma is associated with persistent lung inflammation and long-term remodelling of the airways that have proved refractory to conventional treatments such as steroids, despite their efficacy in controlling acute airway contraction and bronchial inflammation. As its recent dramatic increase in industrialised countries has not been mirrored in developing regions, it has been suggested that helminth infection may protect humans against developing asthma. Consistent with this, ES-62, an immunomodulator secreted by the parasitic worm Acanthocheilonema viteae, can prevent pathology associated with chronic asthma (cellular infiltration of the lungs, particularly neutrophils and mast cells, mucus hyper-production and airway thickening) in an experimental mouse model. Importantly, ES-62 can act even after airway remodelling has been established, arresting pathogenesis and ameliorating the inflammatory flares resulting from repeated exposure to allergen that are a debilitating feature of severe chronic asthma. Moreover, two chemical analogues of ES-62, 11a and 12b mimic its therapeutic actions in restoring levels of regulatory B cells and suppressing neutrophil and mast cell responses. These studies therefore provide a platform ...Continue Reading

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Citations

Oct 20, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·James DoonanWilliam Harnett
Sep 29, 2020·Frontiers in Immunology·Sinéad RyanSinéad Weldon
Jan 27, 2021·Trends in Molecular Medicine·Katherine E Lothstein, William C Gause
Oct 30, 2020·Journal of Asthma and Allergy·Birhanu AyelignTewodros Shibabaw
Oct 27, 2020·Frontiers in Immunology·Francesca AlessandriniMelanie Albrecht

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Methods Mentioned

BETA
SMA
bronchoalveolar lavage
PMA
bronchoalveolar
lavage
SMAs

Software Mentioned

Applied
Zeiss LSM Image Browser
GraphPad Prism
Biosystems
TreeStar
FlowJo

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