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

Research output: Contribution to journalArticle

1 Citation (Scopus)

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

Fingerprint

worms
Phosphorylcholine
Helminths
Medical problems
Type 1 Diabetes Mellitus
Inflammatory Bowel Diseases
Multiple Sclerosis
mice
Respiratory Hypersensitivity
Acanthocheilonema
Anti-Inflammatory Agents
Molecules
Gerbillinae
products
Systemic Lupus Erythematosus
analogs
parasites
molecules
arthritis
Rheumatoid Arthritis

Keywords

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

Cite this

Doonan, James ; Thomas, David ; Wong, Michelle H. ; Ramage, Hazel J. ; Al-Riyami, Lamyaa ; Lumb, Felicity E. ; Bell, Kara S. ; Fairlie-Clarke, Karen J. ; Suckling, Colin J. ; Michelsen, Kathrin S. ; Jiang, Hui-Rong ; Cooke, Anne ; Harnett, Margaret M. ; Harnett, William. / 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. In: Molecules. 2018 ; Vol. 23, No. 10.
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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. / Doonan, James; Thomas, David ; Wong, Michelle H. ; Ramage, Hazel J.; Al-Riyami, Lamyaa; Lumb, Felicity E.; Bell, Kara S.; Fairlie-Clarke, Karen J.; Suckling, Colin J.; Michelsen, Kathrin S. ; Jiang, Hui-Rong; Cooke, Anne ; Harnett, Margaret M.; Harnett, William.

In: Molecules, Vol. 23, No. 10, 2669, 17.10.2018.

Research output: Contribution to journalArticle

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T1 - 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

AU - Doonan, James

AU - Thomas, David

AU - Wong, Michelle H.

AU - Ramage, Hazel J.

AU - Al-Riyami, Lamyaa

AU - Lumb, Felicity E.

AU - Bell, Kara S.

AU - Fairlie-Clarke, Karen J.

AU - Suckling, Colin J.

AU - Michelsen, Kathrin S.

AU - Jiang, Hui-Rong

AU - Cooke, Anne

AU - Harnett, Margaret M.

AU - Harnett, William

PY - 2018/10/17

Y1 - 2018/10/17

N2 - 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.

AB - 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.

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KW - inflammatory bowel disease

KW - multiple sclerosis

KW - nematode

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