SBIR Phase I: A Platform for Anthelmintic Drug Discovery using DAF-12 as a Novel Target

This Small Business Innovation Research (SBIR) Phase I project creates a drug-screening platform for discovery of new antiparasitic drugs. Resistance to current drug treatments is on the rise. New antiparasitic drugs under development are mostly focused on neurotransmission targets, yet a new target has recently emerged, the daf-12 gene. Knudra uses a core expertise in nematode bioengineering to insert parasite genes into the C. elegans roundworm. Drug candidates are found against the parasite gene by the use of biosensor backgrounds, which use fluorescent gene-expression reporters that turn red upon detection of antiparasitic activity. Phase I feasibility is demonstrated when known agonist and antagonist of DAF-12 elicit expected activity on the parasite gene. The platform may then be used to screen compound libraries to find candidates for anthelmintic use. The broader impact/commercial potential of this project, if successful, will be the creation of a screening platform for finding antiparasitics to help in the battle against important diseases such as elephantiasis, river blindness, trichinosis, Enterobiasis (pinworm), and parasitic infections in livestock and crops. Parasitic infection in livestock and humans currently are treated with more than 20 drugs on the market, but some are toxic and carry black box warnings. Food and health security throughout the world would be enhanced with the development of new antiparasites that are safer and more effective. In addition, the technology will help to bring clarity of understanding to the biology of infective-state formation in parasite lifecycle.