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)
|
Text
173622.pdf - Published Version Available under License Creative Commons Attribution. 3MB |
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: | Jiang, Dr Hui-Rong and Fairlie-Clarke, Dr Karen and Harnett, Professor Margaret and Lumb, Miss Felicity and Harnett, Professor William and Doonan, Dr James |
| 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 > School of Infection & Immunity College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine |
| 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 |
University Staff: Request a correction | Enlighten Editors: Update this record
Funder and Project Information
Funder and Project Information