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Indeed, any doubt in the value of nematode neuromuscular function as
a resource for anthelmintic targets is dispelled by the fact that the three
most recent additions to this drug arsenal (derquantel, emodepside, and
monepantel) are embedded within it.
While recent additions to the anthelmintic portfolio are extremely
welcome, this cannot be allowed to encourage complacency in efforts to
diversify the parasiticide arsenal. In addition to remaining gaps in avail-
able anthelmintic therapies, an inevitable consequence of the repeated use
of drugs of this kind is resistance. Drug resistance in nematodes of live-
stock is well established and continues to undermine animal health and
food security. Further, the expanding mass distribution and treatment
approaches to the control of human helminthiases heighten the threat of
resistance in nematode parasites of medical importance (see Chapter 15).
While vaccines fail to meet nematode parasite control needs, anthelmintics
will continue to shoulder the control burden and drug resistance will
ensure the relentless erosion of these control options. Therefore, sustaining
effective control of nematode parasites demands the continual addition of
newmechanism of action anthelmintics to the pharmaceutical arsenal. The
potential of LGCCs and of diverse elements of neuropeptide signaling in
nematode parasites as targets for future anthelmintics is particularly
compelling and has been reviewed recently. 27,49
As the leading model for research on nematode neuromuscular phys-
iology, A. suum is well placed to continue to inform research on anthel-
mintics. The recent completion of its genome 28 and published reports of its
amenability to RNAi 100,101 provide clear opportunities to expand the
utility of Ascaris beyond that of a model to inform basic neuroscience to
a platform for the discovery and validation of new anthelmintic targets.
RNAi-based reverse genetic approaches in animal parasitic nematodes
have proven unreliable 102 e 106 , undermining the exploitation of this tech-
nology to inform gene function and target validation. Several studies
report successful RNAi in larval stage A. suum indicating that the gene
silencing effectors are functional in Ascaris, at least in the larval
stages. 100,101 Recent work has demonstrated robust RNAi of gene targets in
neuronal and non-neuronal tissues of adult female A. suum (unpublished
observations, Neil Warnock, Ciaran McCoy, Nikki Marks, and Angela
Mousley, Queen's University Belfast), providing much hope that Ascaris
can become a powerful tool for the functional genomics of animal parasitic
nematodes.
It seems highly likely that the key advantages offered to neurobiology
research by Ascaris will ensure that it remains at the forefront of neuro-
biology research for some considerable time. Among parasites, Ascaris
provides a totally unique platform for the interrogation of new compo-
nents of neuromuscular signaling, informing the mechanisms of action of
new anthelmintics, facilitating the discovery of novel signaling molecules
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