Discovery and Development of New Antifilarial Drugs

Discovery and Development of New Antifilarial Drugs (In Vitro Assays)

The worldwide threat represente d by filarial species has imposed challenging research initiatives among academic and private contributors toward identifying novel or complementary antiparasitic treatments.

As a result, past decades have seen the emergence of a variety of nematode-applied drug screening methods.

Some of them consisted in revisiting classical assays directly inherited from model organisms such as the free-living nematode Caenorhabditis elegans or the strongyle parasite Haemonchus contortus . Such methods often imply phenotypic observation of hit compound effect on the motility/locomotion or the development of different nematode instars. Applied to filarial species, the use of the dog heartworm model Dirofilaria immitis has highlighted supplementary challenges imposed by the species life cycle and maintenance requirements, which imposes a reflection on alternative assays to ease screening processes and further in vivo testing.

The era of microfluidic technologies represents a source of powerful tools, which would enable fine characterization of phenotypic effects induced by any active ingredient in development.

The motility trap assay, currently adapted to strongyle species, is one of the most recent accomplishments in combining motility observation and automated recording in a nematode-applied fluidic device. As a result, the MTA enables fine anthelmintic sensitivity assessment and fills the gaps of classical methods as it dramatically reduces the duration of the assay, the number of required animals, and enable the detection of relevant and more representative effective concentrations.

In summary, the preliminary data presented in this chapter reflect a novel standardized approach that has the potential to be applied to filariid species, a prospective that is hoped to stimulate a new dynamic in anthelmintic research.

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