A team of scientists from UC Riverside, UC Irvine, and Yale School of Medicine have developed a new drug called MED6-189 to combat Plasmodium falciparum, the most deadly human malaria parasite responsible for nearly 619,000 global deaths in 2022. MED6-189 has shown effectiveness against both drug-sensitive and drug-resistant strains of the parasite in vitro and in a humanized mouse model. The drug targets and disrupts the apicoplast, an organelle found in P. falciparum cells, as well as the vesicular trafficking pathways, preventing the parasite from developing resistance and eliminating infection in red blood cells.
This breakthrough in malaria research was published in the journal Science, where the researchers detailed how MED6-189 works by disrupting the apicoplast and vesicular trafficking to block the parasite’s development. The compound was found to be potent against other zoonotic Plasmodium parasites, such as P. knowlesi and P. cynomolgi, making it a promising lead in the fight against malaria. MED6-189, inspired by a compound extracted from marine sponges, was synthesized by the lab of Christopher Vanderwal at UC Irvine. The compound’s ability to target multiple pathways in P. falciparum is crucial in preventing the parasite from developing resistance quickly.
When tested on mice infected with P. falciparum, researchers at GSK in Spain found that MED6-189 successfully cleared the mice of the parasite. Collaborating with Choukri Ben Mamoun at Yale School of Medicine, the team also tested the compound on P. knowlesi, a parasite that infects monkeys, and saw similar promising results. The next steps for the team involve optimizing MED6-189 and further confirming its mechanisms of action using a systems biology approach, which allows researchers to understand how different organisms and cells interact on a larger scale.
The research was a collaborative effort involving scientists from various institutions, including the Stowers Institute for Medical Research, GSK, and the University of Georgia. Funding for the research was provided by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health, supporting the work of lead researchers Karine Le Roch, Christopher Vanderwal, and Choukri Ben Mamoun. Le Roch, who directs the Center for Infectious Disease and Vector Research at UCR, highlighted the importance of developing new antimalarial compounds like MED6-189 to combat the growing resistance of malaria parasites to existing drugs.
Overall, the development of MED6-189 represents a significant advancement in the fight against malaria, a disease that continues to claim hundreds of thousands of lives each year. The compound’s ability to target multiple pathways in P. falciparum, while preventing the development of resistance, makes it a valuable asset in the quest to eradicate malaria worldwide. Continued research and optimization of MED6-189, along with further understanding of its mechanisms of action through a systems biology approach, will be crucial in developing effective treatments for malaria and saving lives in the future.
