New drugs tackle difficult nematodes

Researchers have discovered what could be the first major new class of drugs in 25 years for treating animals infested with parasitic nematodes.

Three main classes of drugs have been used for decades, and nematode resistance is now widespread, says Ronald Kaminsky of the Novartis Animal Health Research Center in St. Aubin, Switzerland. A fourth drug class has so far been approved only for cats.

Nematodes, or roundworms, that infest the gut can weaken or kill their animal hosts. For example, the barber’s pole worm (Haemonchus contortus), named for its spiraling red intestine, sucks blood fiercely enough to cause severe anemia.

Compounds called AADs, or aminoacetonitrile derivatives, kill barber’s pole worms, even those resistant to current drugs, Kaminsky and an international team of colleagues report in the March 13 Nature.

While trying to figure out how the substances work, researchers found that Caenorhabditis elegans, or lab nematodes, reacted to the AADs as if dosed with a chemical known to interfere with acetylcholine receptors. Yet the reactions differed if nematodes got an old drug, which blasts a specific subset of the receptors. Therefore, the AADs might be attacking a different subset of receptors, possibly a new target for veterinary drugs.

To test this idea, researchers bred both lab nematodes and barber’s pole worms to resist the AADs. Analyzing the genes that allowed the mutants to survive, the researchers saw that AADs target a type of receptor that mammal acetylcholine systems don’t use. Thus an AAD drug would kill the parasitic nematodes but not the sheep, goats, or, perhaps one day, people.

“Elegant work,” comments Roger Prichard of McGill University in Montreal.