Researchers at the University of California, Riverside are working to develop new treatments for malaria and babesiosis as parasites become increasingly resistant to existing drugs, according to a July 31 announcement. The National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, has awarded two collaborative grants totaling more than $8 million to researchers at UC Riverside, UC Irvine, and Yale University. Through these awards, UC Riverside will receive more than $2.5 million.
The projects focus on malaria—a disease that continues to kill hundreds of thousands worldwide each year—and babesiosis, a tick-borne illness that is becoming more common in the United States as tick populations expand. Both diseases are caused by closely related parasites that invade red blood cells. This similarity allows researchers to pursue treatments effective against both conditions.
The research builds on years of collaboration among Le Roch from UC Riverside, Christopher Vanderwal from UC Irvine, and Choukri Ben Mamoun from Yale University. The teams combine expertise in medicinal chemistry, genetics, parasite biology, systems biology, and animal models with the aim of transforming naturally occurring compounds into potential medicines.
“We already have promising lead compounds that are highly active against both Plasmodium and Babesia,” said Le Roch, director of UCR's Center for Infectious Disease and Vector Research. “Now the goal is to move those lead compounds toward preclinical development.” One project focuses on leelamine-derived isonitriles (LDIs), synthesized from pine bark; another investigates pyrroloiminoquinones (PIQs), isolated from marine sponges. Both compound classes have shown potent activity against drug-resistant strains.
Le Roch said natural products have provided foundations for many important medicines but can be difficult or expensive to manufacture due to their complexity: “These compounds are usually extremely effective, but they are also very complex molecules,” she said. “These two projects focus on compounds that are easier and much less expensive to synthesize.” Over five years, the team will optimize LDIs and PIQs for safety and effectiveness in laboratory settings while identifying their mechanisms against parasites.
“We hope to demonstrate that they target completely different pathways than the treatments currently being used,” Le Roch said. “That's likely because both classes of compounds are active against drug-resistant parasite strains.” She added: “We're aiming not only to kill the parasite but also to stop transmission... Ultimately, the goal would be to develop an oral treatment.”
Le Roch’s laboratory will use systems biology approaches while Vanderwal’s group synthesizes compounds; Ben Mamoun’s lab will evaluate them in animal models with a focus on babesiosis studies. The findings could impact other apicomplexan parasites beyond malaria and babesiosis—including Toxoplasma—and support undergraduate and graduate training at UCR.
“Funding projects like these is essential,” Le Roch said. “It allows us to train the next generation of scientists and develop treatments that could help people.” For her measure of success: "I really want these compounds to move to the next step in preclinical and clinical trials," she said.
