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 › peer-review

18 Citations (Scopus)

50 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

Access to Document

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

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), Article 2669. https://doi.org/10.3390/molecules23102669

@article{0ce559de7478408fa4d9f3a8e9bba5a8,

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.",

keywords = "ES-62, helminth, inflammatory bowel disease, multiple sclerosis, nematode, type 1 diabetes",

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",

year = "2018",

month = oct,

day = "17",

doi = "10.3390/molecules23102669",

language = "English",

volume = "23",

journal = "Molecules",

issn = "1420-3049",

publisher = "MDPI AG",

number = "10",

}

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

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

SN - 1420-3049

VL - 23

JO - Molecules

JF - Molecules

IS - 10

M1 - 2669

ER -

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

Keywords

Access to Document

Other files and links

Fingerprint

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

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

Cite this

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

Keywords

Access to Document

Other files and links

Fingerprint

Projects

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

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

Cite this