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Molecules. 2018 Oct 17;23(10). pii: E2669. doi: 10.3390/molecules23102669.

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.

Author information

1
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, UK. james.doonan@strath.ac.uk.
2
Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK. tdct2@cam.ac.uk.
3
F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. Michelle.Wong@cshs.org.
4
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, UK. hazeljramage@gmail.com.
5
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, UK. lamyaa.alriyami@gmail.com.
6
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, UK. felicity.lumb@strath.ac.uk.
7
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, UK. karabell@hotmail.co.uk.
8
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, UK. karenfairlieclarke@gmail.com.
9
Department of Pure & Applied Chemistry, University of Strathclyde, Glasgow G1 1XL, UK. c.j.suckling@strath.ac.uk.
10
F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. Kathrin.Michelsen@cshs.org.
11
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, UK. huirong.jiang@strath.ac.uk.
12
Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK. ac416@cam.ac.uk.
13
Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TA, UK. margaret.harnett@glasgow.ac.uk.
14
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, UK. w.harnett@strath.ac.uk.

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.

KEYWORDS:

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

PMID:
30336585
PMCID:
PMC6222842
DOI:
10.3390/molecules23102669
[Indexed for MEDLINE]
Free PMC Article

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