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
Affiliations
James Doonan
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, UK
David Thomas
Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK
Michelle H. Wong
F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
Hazel J. Ramage
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, UK
Lamyaa Al-Riyami
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, UK
Felicity E. Lumb
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, UK
Kara S. Bell
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, UK
Karen J. Fairlie-Clarke
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, UK
Colin J. Suckling
Department of Pure & Applied Chemistry, University of Strathclyde, Glasgow G1 1XL, UK
Kathrin S. Michelsen
F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
Hui-Rong Jiang
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, UK
Anne Cooke
Department of Pathology, University of Cambridge, Cambridge CB2 1QP, UK
Margaret M. Harnett
Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TA, UK
William Harnett
Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow G4 0RE, UK
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.
