Inhibitors for AutoPhagy and DCAR-1 as Novel Anthelmintic Drugs

Parasitic roundworms infect over a billion people every year and cause blindness, anemia, intestinal disease, respiratory disorders, disfigurement of limbs and organs, often leading to severe morbidity and death. Transmission to humans often occurs through ingestion of food or interaction with infected animals. Over a billion dollars is spent annually to prevent worms from infecting animals while the economic loss exceeds $100 billion worldwide. An increasing number of infections coupled with the rise in resistance of existing drug therapies for humans and animals are increasing the demand for novel therapeutics options.

Controlling parasitic nematodes can be accomplished by modifying food supply, temperature, and molecular signaling pathways within the organism. A high ratio of pheromones to food produces parasite formation and maintenance, while a low ratio enhances growth and stimulates recovery of larvae. Changes in temperature along with food/pheromone ratios have also been shown to modulate growth.

This invention is a therapeutic that modulates autophagy, a process in which an organism disassembles an unnecessary or dysfunctional cellular component, and a molecule called DCAR-1, as potential anti-parasitic drugs. Recent studies have demonstrated the importance of these molecules for the viability of deadly parasites. Initial in vivo studies demonstrate reduction of autophagy and DCAR-1 by these novel drugs inhibit larvae recovery and suppress growth in the laboratory. Additionally, evidence suggests the therapy can be used as a preventive measure to help stop the infection before it begins.