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 -