Janicova, L., Rzepecka, J., Rodgers, D.T., Doonan, J., Bell, K.S., Lumb, F.E., Suckling, C.J., Harnett, M.M. and Harnett, W. (2016) Testing small molecule analogues of theAcanthocheilonema viteaeimmunomodulator ES-62 against clinically relevant allergens. Parasite Immunology, 38(6), pp. 340-351. (doi: 10.1111/pim.12322) (PMID:27059010) (PMCID:PMC4913752)
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Abstract
ES-62 is a glycoprotein secreted by the filarial nematode Acanthocheilonema viteae that protects against ovalbumin (OVA)-induced airway hyper-responsiveness in mice by virtue of covalently attached anti-inflammatory phosphorylcholine (PC) residues. We have recently generated a library of small molecule analogues (SMAs) of ES-62 based around its active PC moiety as a starting point in novel drug development for asthma and identified two compounds – termed 11a and 12b – that mirror ES-62's protective effects. In this study, we have moved away from OVA, a model allergen, to test the SMAs against two clinically relevant allergens – house dust mite (HDM) and cockroach allergen (CR) extract. We show that both SMAs offer some protection against development of lung allergic responses to CR, in particular reducing eosinophil infiltration, whereas only SMA 12b is effective in protecting against eosinophil-dependent HDM-induced allergy. These data therefore suggest that helminth molecule-induced protection against model allergens may not necessarily translate to clinically relevant allergens. Nevertheless, in this study, we have managed to demonstrate that it is possible to produce synthetic drug-like molecules based on a parasitic worm product that show therapeutic potential with respect to asthma resulting from known triggers in humans.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Harnett, Professor Margaret and Lumb, Miss Felicity and Harnett, Professor William and Doonan, Dr James and Rodgers, Professor Dennis |
| Authors: | Janicova, L., Rzepecka, J., Rodgers, D.T., Doonan, J., Bell, K.S., Lumb, F.E., Suckling, C.J., Harnett, M.M., and Harnett, W. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity College of Social Sciences > School of Social and Political Sciences |
| Journal Name: | Parasite Immunology |
| Publisher: | Wiley |
| ISSN: | 0141-9838 |
| ISSN (Online): | 1365-3024 |
| Published Online: | 30 May 2016 |
| Copyright Holders: | Copyright © 2016 The Authors |
| First Published: | First published in Parasite Immunology 38(6): 340-351 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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