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

James Doonan, David Thomas, Michelle H. Wong, Hazel J. Ramage, Lamyaa Al-Riyami, Felicity E. Lumb, Kara S. Bell, Karen J. Fairlie-Clarke, Colin J. Suckling, Kathrin S. Michelsen, Hui-Rong Jiang, Anne Cooke, Margaret M. Harnett, William Harnett

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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.
Original languageEnglish
Article number2669
Number of pages14
JournalMolecules
Volume23
Issue number10
DOIs
Publication statusPublished - 17 Oct 2018

Keywords

  • ES-62
  • helminth
  • inflammatory bowel disease
  • multiple sclerosis
  • nematode
  • type 1 diabetes

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    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., & Harnett, W. (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]. https://doi.org/10.3390/molecules23102669