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

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

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 journal › Article

4 Citations (Scopus)

9 Downloads (Pure)

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 language	English
Article number	2669
Number of pages	14
Journal	Molecules
Volume	23
Issue number	10
DOIs	https://doi.org/10.3390/molecules23102669
Publication status	Published - 17 Oct 2018

Keywords

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

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10.3390/molecules23102669Licence: CC BY 4.0

Doonan-etal-Molecules-2018-Failure-of-the-anti-inflammatory-parasitic-worm-product-ES-62-to-provide-protectionFinal published version, 3.64 MBLicence: CC BY 4.0

https://www.mdpi.com/journal/molecules

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Projects

2 Finished

The Filarial Nematode Immunomodulator Es-62 As A Tool In Novel Drug Development For Mast Cell-Dependent Inflammatory Diseases

Harnett, W.

Wellcome Trust

1/05/09 → 31/08/15

Project: Research

SMALL MOLECULE ANALOGUES (SMA'S) OF AN IMMUNOMDULATORY HELMINTH PRODUCT PROVIDE A NOVEL APPROACH TO DISSECTING MACROPHAGE SIGNAL TRANDUCTION PATHWAYS

Harnett, W. & Suckling, C.

BBSRC (Biotech & Biological Sciences Research Council)

1/05/07 → 31/12/10

Project: Research

Cite this

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

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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title = "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",

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{\textquoteright}s failures in these conditions and how the negative data generated may help us to further understand ES-62{\textquoteright}s mechanism of action.",

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

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Doonan, J, Thomas, D, Wong, MH, Ramage, HJ, Al-Riyami, L, Lumb, FE, Bell, KS, Fairlie-Clarke, KJ, Suckling, CJ, Michelsen, KS, Jiang, H-R, Cooke, A, Harnett, MM & 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, vol. 23, no. 10, 2669. https://doi.org/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. / 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 journal › Article

TY - JOUR

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.

KW - ES-62

KW - helminth

KW - inflammatory bowel disease

KW - multiple sclerosis

KW - nematode

KW - type 1 diabetes

UR - https://www.mdpi.com/journal/molecules

U2 - 10.3390/molecules23102669

DO - 10.3390/molecules23102669

M3 - Article

VL - 23

JO - Molecules

JF - Molecules

SN - 1420-3049

IS - 10

M1 - 2669

ER -