The Harnett Labs


Protection Against Arthritis by the Parasitic Worm Product ES-62, and Its Drug-Like Small Molecule Analogues, Is Associated With Inhibition of Osteoclastogenesis. Doonan J, Lumb FE, Pineda MA, Tarafdar A, Crowe J, Khan AM, Suckling CJ, Harnett MM, Harnett W. Front Immunol. 2018 May 14;9:1016. doi: 10.3389/fimmu.2018.01016. eCollection 2018. PMID: 29867986

Synthetic analogues of the parasitic worm product ES-62 reduce disease development in in vivo models of lung fibrosis. Suckling CJ, Mukherjee S, Khalaf AI, Narayan A, Scott FJ, Khare S, Dhakshinamoorthy S, Harnett MM, Harnett W. Acta Trop. 2018 May 23;185:212-218. doi: 10.1016/j.actatropica.2018.05.015. PMID: 29802846

IL-33/ST2 signalling and crosstalk with FcεRI and TLR4 is targeted by the parasitic worm product, ES-62. Ball DH, Al-Riyami L, Harnett W, Harnett MM. Sci Rep. 2018 Mar 14;8(1):4497. doi: 10.1038/s41598-018-22716-9. PMID:29540770

Small Molecule Analogues of the parasitic worm product ES-62 interact with the TIR domain of MyD88 to inhibit pro-inflammatory signalling. Suckling CJ, Alam S, Olson MA, Saikh KU, Harnett MM, Harnett W. Sci Rep. 2018 Feb 1;8(1):2123. doi: 10.1038/s41598-018-20388-z. PMID:29391452 Dendritic cells provide a therapeutic target for synthetic small molecule analogues of the parasitic worm product, ES-62. Lumb FE, Doonan J, Bell KS, Pineda MA, Corbet M, Suckling CJ, Harnett MM, Harnett W. Sci Rep. 2017 May 10;7(1):1704. doi: 10.1038/s41598-017-01651-1. PMID: 28490801


Dendritic cells provide a therapeutic target for synthetic small molecule analogues of the parasitic worm product, ES-62. Lumb FE, Doonan J, Bell KS, Pineda MA, Corbet M, Suckling CJ, Harnett MM, Harnett W. Sci Rep. 2017 May 10;7(1):1704. doi: 10.1038/s41598-017-01651-1.PMID:28490801


The helminth product, ES-62 modulates dendritic cell responses by inducing the selective autophagolysosomal degradation of TLR-transducers, as exemplified by PKCδ. Eason RJ, Bell KS, Marshall FA, Rodgers DT, Pineda MA, Steiger CN, Al-Riyami L, Harnett W, Harnett MM. Sci Rep. 2016 Nov 21;6:37276. doi: 10.1038/srep37276. PMID: 27869138

Janicova L, Rzepecka J, Rodgers DT, Doonan J, Bell KS, Lumb FE, Suckling CJ, Harnett MM, Harnett W. Testing small molecule analogues of the Acanthocheilonema viteae immunomodulator ES-62 against clinically relevant allergens. Parasite Immunology, 2016 Apr 1; 28, 340-351. doi: 10.1111/pim.12322

Ahmed UK, Maller NC, Iqbal AJ, Al-Riyami L, Harnett W, Raynes JG. The Carbohydrate-linked Phosphorylcholine of the Parasitic Nematode product ES-62 modulates Complement activation. J Biol Chem. 2016 Apr 4. pii: jbc.M115.702746.
[Epub ahead of print] PubMed PMID: 27044740.

Mouser EE, Pollakis G, Yazdanbakhsh M, Harnett W, de Jong EC, Paxton WA. Brugia malayi Antigen (BmA) Inhibits HIV-1 Trans-Infection but Neither BmA nor ES-62 Alter HIV-1 Infectivity of DC Induced CD4+ Th-Cells. PLoS One. 2016 Jan 25;11(1):e0146527. doi: 10.1371/journal.pone.0146527. eCollection 2016. PubMed PMID: 26808476; PubMed Central PMCID: PMC4726616.

Coltherd JC, Rodgers DT, Lawrie RE, Al-Riyami L, Suckling CJ, Harnett W, Harnett MM. The parasitic worm-derived immunomodulator, ES-62 and its drug-like small molecule analogues exhibit therapeutic potential in a model of chronic asthma. Sci Rep. 2016 Jan 14;6:19224. doi: 10.1038/srep19224. PubMed PMID: 26763929; PubMed Central PMCID: PMC4725896.


Bell KS, Al-Riyami L, Lumb FE, Britton GJ, Poole AW, Williams CM, Braun U, Leitges M, Harnett MM, Harnett W. The role of individual protein kinase C isoforms in mouse mast cell function and their targeting by the immunomodulatory  parasitic worm product, ES-62. Immunol Lett. 2015 Nov;168(1):31-40. doi: 10.1016/j.imlet.2015.09.001. Epub 2015 Sep 3. PubMed PMID: 26343793; PubMed Central PMCID: PMC4643489.

Rodgers DT, Pineda MA, Suckling CJ, Harnett W, Harnett MM. Drug-like analogues of the parasitic worm-derived immunomodulator ES-62 are therapeutic in the MRL/Lpr model of systemic lupus erythematosus. Lupus. 2015 Nov;24(13):1437-42. doi: 10.1177/0961203315591031. Epub 2015 Jun 17. PubMed PMID: 26085597; PubMed Central PMCID: PMC4616909.

Rzepecka J, Pineda MA, Al-Riyami L, Rodgers DT, Huggan JK, Lumb FE, Khalaf AI, Meakin PJ, Corbet M, Ashford ML, Suckling CJ, Harnett MM, Harnett W. Prophylactic and therapeutic treatment with a synthetic analogue of a parasitic worm product prevents experimental arthritis and inhibits IL-1b production via NRF2-mediated counter-regulation of the inflammasome. J Autoimmun. 2015 Jun;60:59-73. doi: 10.1016/j.jaut.2015.04.005. Epub 2015 May 11. PubMed PMID: 25975491; PubMed Central PMCID: PMC4459730.

Al-Riyami L, Rodgers DT, Rzepecka J, Pineda MA, Suckling CJ, Harnett MM, Harnett W. Protective effect of small molecule analogues of the Acanthocheilonema viteae secreted product ES-62 on oxazolone-induced ear inflammation. Exp Parasitol. 2015 Nov;158:18-22. doi: 10.1016/j.exppara.2015.03.025. Epub 2015 Mar 30. PubMed PMID: 25836375; PubMed Central PMCID: PMC4659540.

Pineda MA, Eason RJ, Harnett MM, Harnett W. From the worm to the pill, the parasitic worm product ES-62 raises new horizons in the treatment of rheumatoid arthritis. Lupus. 2015 Apr;24(4-5):400-11. doi: 10.1177/0961203314560004. Review.
PubMed PMID: 25801883.

Aprahamian TR, Zhong X, Amir S, Binder CJ, Chiang LK, Al-Riyami L, Gharakhanian R, Harnett MM, Harnett W, Rifkin IR. The immunomodulatory parasitic  worm product ES-62 reduces lupus-associated accelerated atherosclerosis in a mouse model. Int J Parasitol. 2015 Mar;45(4):203-7. doi: 10.1016/j.ijpara.2014.12.006. Epub 2015 Feb 7. PubMed PMID: 25666929; PubMed Central PMCID: PMC4355381.

Rodgers DT, McGrath MA, Pineda MA, Al-Riyami L, Rzepecka J, Lumb F, Harnett W, Harnett MM. The parasitic worm product ES-62 targets myeloid differentiation factor 88-dependent effector mechanisms to suppress antinuclear antibody production and proteinuria in MRL/lpr mice. Arthritis Rheumatol. 2015 Apr;67(4):1023-35. doi: 10.1002/art.39004. PubMed PMID: 25546822; PubMed Central  PMCID: PMC4409857.


Rzepecka J, Coates ML, Saggar M, Al-Riyami L, Coltherd J, Tay HK, Huggan JK,  Janicova L, Khalaf AI, Siebeke I, Suckling CJ, Harnett MM, Harnett W. Small molecule analogues of the immunomodulatory parasitic helminth product ES-62 have anti-allergy properties. Int J Parasitol. 2014 Aug;44(9):669-74. doi: 10.1016/j.ijpara.2014.05.001. Epub 2014 Jun 12. PubMed PMID: 24929132; PubMed Central PMCID: PMC4119935.

Rodgers DT, Pineda MA, McGrath MA, Al-Riyami L, Harnett W, Harnett MM. Protection against collagen-induced arthritis in mice afforded by the parasitic worm product, ES-62, is associated with restoration of the levels of interleukin-10-producing B cells and reduced plasma cell infiltration of the joints. Immunology. 2014 Mar;141(3):457-66. doi: 10.1111/imm.12208. PubMed PMID: 24708419; PubMed Central PMCID: PMC3930382.

Harnett W. Secretory products of helminth parasites as immunomodulators. Mol  Biochem Parasitol. 2014 Jul;195(2):130-6. doi: 10.1016/j.molbiopara.2014.03.007.  Epub 2014 Apr 3. Review. PubMed PMID: 24704440.

Pineda MA, Lumb F, Harnett MM, Harnett W. ES-62, a therapeutic anti-inflammatory agent evolved by the filarial nematode Acanthocheilonema viteae. Mol Biochem Parasitol. 2014 Mar-Apr;194(1-2):1-8. doi: 10.1016/j.molbiopara.2014.03.003. Epub 2014 Mar 23. Review. PubMed PMID: 24671112.

Pineda MA, Al-Riyami L, Harnett W, Harnett MM. Lessons from helminth infections: ES-62 highlights new interventional approaches in rheumatoid arthritis. Clin Exp Immunol. 2014 Jul;177(1):13-23. doi: 10.1111/cei.12252. Review. PubMed PMID: 24666108; PubMed Central PMCID: PMC4089150.

Pineda MA, Rodgers DT, Al-Riyami L, Harnett W, Harnett MM. ES-62 protects against collagen-induced arthritis by resetting interleukin-22 toward resolution  of inflammation in the joints. Arthritis Rheumatol. 2014 Jun;66(6):1492-503. doi: 10.1002/art.38392. PubMed PMID: 24497523; PubMed Central PMCID: PMC4737104.

Harnett MM, Harnett W, Pineda MA. The parasitic worm product ES-62 up-regulates IL-22 production by yd T cells in the murine model of Collagen-Induced Arthritis. Inflamm Cell Signal. 2014;1(5). pii: 308. PubMed PMID: 26594650; PubMed Central PMCID: PMC4650209.

Key Older Papers

Al-Riyami L, Pineda MA, Rzepecka J, Huggan JK, Khalaf AI, Suckling CJ, Scott FJ, Rodgers DT, Harnett MM, Harnett W. Designing anti-inflammatory drugs from parasitic worms: a synthetic small molecule analogue of the Acanthocheilonema viteae product ES-62 prevents development of collagen-induced arthritis. J Med Chem. 2013 Dec 27;56(24):9982-10002. doi: 10.1021/jm401251p. Epub 2013 Nov 25. PubMed PMID: 24228757; PubMed Central PMCID: PMC4125414.

Paunovic V, Harnett MM. Mitogen-activated protein kinases as therapeutic targets for rheumatoid arthritis. Drugs. 2013 Feb;73(2):101-15. doi: 10.1007/s40265-013-0014-6. Review. PubMed PMID: 23371304.

Rzepecka J, Siebeke I, Coltherd JC, Kean DE, Steiger CN, Al-Riyami L, McSharry C, Harnett MM, Harnett W. The helminth product, ES-62, protects against airway inflammation by resetting the Th cell phenotype. Int J Parasitol. 2013 Mar;43(3-4):211-23. doi: 10.1016/j.ijpara.2012.12.001. Epub 2013 Jan 3. PubMed PMID: 23291461; PubMed Central PMCID: PMC3584281.

Pineda MA, McGrath MA, Smith PC, Al-Riyami L, Rzepecka J, Gracie JA, Harnett W, Harnett MM. The parasitic helminth product ES-62 suppresses pathogenesis in collagen-induced arthritis by targeting the interleukin-17-producing cellular network at multiple sites. Arthritis Rheum. 2012 Oct;64(10):3168-78. doi: 10.1002/art.34581. PubMed PMID: 22729944.Harnett W, Harnett MM. Helminth-derived immunomodulators: can understanding the worm produce the pill? Nat Rev Immunol. 2010 Apr;10(4):278-84. doi: 10.1038/nri2730. Epub 2010 Mar 12. Review. PubMed PMID: 20224568.

Melendez AJ, Harnett MM, Pushparaj PN, Wong WS, Tay HK, McSharry CP, Harnett  W. Inhibition of Fc epsilon RI-mediated mast cell responses by ES-62, a product of parasitic filarial nematodes. Nat Med. 2007 Nov;13(11):1375-81. Epub 2007 Oct  21. PubMed PMID: 17952092.

Harnett MM, Kean DE, Boitelle A, McGuiness S, Thalhamer T, Steiger CN, Egan C, Al-Riyami L, Alcocer MJ, Houston KM, Gracie JA, McInnes IB, Harnett W. The phosphorycholine moiety of the filarial nematode immunomodulator ES-62 is responsible for its anti-inflammatory action in arthritis. Ann Rheum Dis. 2008 Apr;67(4):518-23. Epub 2007 Aug 17. PubMed PMID: 17704067.

Goodridge HS, McGuiness S, Houston KM, Egan CA, Al-Riyami L, Alcocer MJ, Harnett MM, Harnett W. Phosphorylcholine mimics the effects of ES-62 on macrophages and dendritic cells. Parasite Immunol. 2007 Mar;29(3):127-37. PubMed
PMID: 17266740.

Goodridge HS, Marshall FA, Else KJ, Houston KM, Egan C, Al-Riyami L, Liew FY, Harnett W, Harnett MM. Immunomodulation via novel use of TLR4 by the filarial nematode phosphorylcholine-containing secreted product, ES-62. J Immunol. 2005 Jan 1;174(1):284-93. PubMed PMID: 15611251.

McInnes IB, Leung BP, Harnett M, Gracie JA, Liew FY, Harnett W. A novel therapeutic approach targeting articular inflammation using the filarial nematode-derived phosphorylcholine-containing glycoprotein ES-62. J Immunol. 2003 Aug 15;171(4):2127-33. PubMed PMID: 12902519.