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

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Doonan, James and Thomas, David and Wong, Michelle H. and Ramage, Hazel J. and Al-Riyami, Lamyaa and Lumb, Felicity E. and Bell, Kara S. and Fairlie-Clarke, Karen J. and Suckling, Colin J. and Michelsen, Kathrin S. and Jiang, Hui-Rong and Cooke, Anne and Harnett, Margaret M. and Harnett, William (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. ISSN 1420-3049 (https://doi.org/10.3390/molecules23102669)

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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.

ORCID iDs

Doonan, James ORCID logoORCID: https://orcid.org/0000-0001-6933-4840, Thomas, David, Wong, Michelle H., Ramage, Hazel J. ORCID logoORCID: https://orcid.org/0000-0002-1110-1769, Al-Riyami, Lamyaa, Lumb, Felicity E. ORCID logoORCID: https://orcid.org/0000-0001-9742-5125, Bell, Kara S., Fairlie-Clarke, Karen J., Suckling, Colin J., Michelsen, Kathrin S., Jiang, Hui-Rong, Cooke, Anne, Harnett, Margaret M. and Harnett, William ORCID logoORCID: https://orcid.org/0000-0001-9545-9401;
CORE (COnnecting REpositories)