Failure of the anti-inflammatory parasitic worm product ES-62 to provide protection in mouse models of type I diabetes, multiple sclerosis, and inflammatory bowel disease

Doonan, J. et al. (2018) Failure of the anti-inflammatory parasitic worm product ES-62 to provide protection in mouse models of type I diabetes, multiple sclerosis, and inflammatory bowel disease. Molecules, 23(10), 2669. (doi: 10.3390/molecules23102669) (PMID:30336585) (PMCID:PMC6222842)

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Abstract

Parasitic helminths and their isolated secreted products show promise as novel treatments for allergic and autoimmune conditions in humans. Foremost amongst the secreted products is ES-62, a glycoprotein derived from Acanthocheilonema viteae, a filarial nematode parasite of gerbils, which is anti-inflammatory by virtue of covalently-attached phosphorylcholine (PC) moieties. ES-62 has been found to protect against disease in mouse models of rheumatoid arthritis, systemic lupus erythematosus, and airway hyper-responsiveness. Furthermore, novel PC-based synthetic small molecule analogues (SMAs) of ES-62 have recently been demonstrated to show similar anti-inflammatory properties to the parent molecule. In spite of these successes, we now show that ES-62 and its SMAs are unable to provide protection in mouse models of certain autoimmune conditions where other helminth species or their secreted products can prevent disease development, namely type I diabetes, multiple sclerosis and inflammatory bowel disease. We speculate on the reasons underlying ES-62's failures in these conditions and how the negative data generated may help us to further understand ES-62's mechanism of action.

Item Type:Articles
Keywords:Helminth, nematode, multiple sclerosis, type 1 diabetes, inflammatory bowel disease, Es-62.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Harnett, Professor Margaret and Lumb, Miss Felicity and Harnett, Professor William and Doonan, Dr James and Fairlie-Clarke, Dr Karen and Jiang, Dr Hui-Rong
Creator Roles:
Harnett, W.Conceptualization, Funding acquisition, Project administration, Writing – original draft
Harnett, M. H.Writing – original draft
Harnett, M. M.Conceptualization, Funding acquisition
Jiang, H.-R.Conceptualization, Investigation, Writing – review and editing
Doonan, J.Investigation, Writing – original draft
Lumb, F. E.Investigation, Writing – review and editing
Fairlie-Clarke, K. J.Investigation
Authors: Doonan, J., Thomas, D., Wong, M. H., Ramage, H. J., Al-Riyami, L., Lumb, F. E., Bell, K. S., Fairlie-Clarke, K. J., Suckling, C. J., Michelsen, K. S., Jiang, H.-R., Cooke, A., Harnett, M. M., and Harnett, W.
College/School:College of Medical Veterinary and Life Sciences > Institute of Biodiversity Animal Health and Comparative Medicine
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Molecules
Publisher:MDPI
ISSN:1420-3049
ISSN (Online):1420-3049
Published Online:17 October 2018
Copyright Holders:Copyright © 2018 The Authors
First Published:First published in Molecules 23(10): 2669
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
455802Small molecule analogues (SMAs) of an immunomodulatory helminth product provide a novel approach to dissecting macrophage signalsMargaret HarnettBiotechnology and Biological Sciences Research Council (BBSRC)BB/E013929/1III -IMMUNOLOGY
495342ES-62, TLR4, the Mast Cell and development of novel drugs for mast cell-mediated inflammationMargaret HarnettWellcome Trust (WELLCOTR)086852/Z/08/ZIII -IMMUNOLOGY