Parasitic nematodes, also known as roundworms, are significant agricultural pests, causing economic losses in the hundreds of billions of dollars for food crops, and tens of billions for livestock. They also pose a significant problem for pet health in the industrialized world, and more important, human health in the developing world. In 2011, sales of the anti-nematode drug Ivermectin exceeded $1 billion. Unfortunately current solutions are becoming obsolete due to emerging resistance to existing drugs, and increasingly stringent environmental regulations. New pesticides and drugs are needed to prevent nematode damage to crops, animals and humans, and this represents a potentially significant economic opportunity we hope to address. This I-Corps team has developed a process that can be used to identify chemical compounds that kill nematode pests in a novel way. In addition, the proposed method can be selective, in that the compounds developed for commercial use can be active against nematodes, and be inactive against humans and other animals. This differentiation will allow users to reduce the environmental toxicity of anti-nematode compounds, a key obstacle to pesticide use today.
The overall goals of this project are to develop and commercialize new chemical compounds that can be used to combat parasitic nematodes in agricultural, veterinary, and human health applications. The team's approach is to screen chemical libraries for compounds that can activate parasite target proteins required for neuronal or muscular function. Exposure to the compound will cause lethal disruption of nematode physiology, which should prevent establishment and promote clearance of nematode infestations. Unfortunately, direct screening of parasitic nematodes is impractical because they are very difficult to culture and genetically manipulate in the lab. To meet this challenge the team has created an innovative method that involves screening genetically engineered laboratory nematodes (C. elegans) expressing parasite targets, such that target activation causes paralysis (an easy to score phenotype amenable to automated screening). ). In contrast to more traditional methods, which utilize cultured mammalian cells, the proposed screen ensures that compounds will be active within the nematode physiological context (i.e. the target is integrated into its normal signaling pathways, and the compound can penetrate the nematode protective cuticle, and is thus bio-available). Customer discovery interviews during the I-Corps program will help the team refine and focus these goals to fill existing market needs for new anti-nematode compounds. The potential contribution of this work will be to bring one new anti-nematode compound to the market, but perhaps more importantly, establish an ongoing pipeline for the discovery and commercialization of future anti-nematode compounds to optimally fit specific market needs in agriculture, veterinary medicine, and human medicine, and to keep ahead of resistance as it emerges.
