New antimalarial drug with novel mechanism of action

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Malaria is a devastating disease that causes significant morbidity and mortality in temperate and tropical regions around the world. Because of the increased prevalence of multidrug-resistant malaria strains, new drugs are urgently required to combat this problem.

In early December, a significant new development was reported by a multidisciplinary team including investigators from the University of South Florida. In a report published in the Proceedings of the National Academy of Sciences, the team describes the efforts to optimize a hit with antimalarial activity into a drug candidate with all the required properties for clinical use to treat malaria. The team is led by Prof. Kip Guy at St. Jude’s Children’s Medical Research Hospital, Dr. David Floyd at Rutgers University, Dr. Joe DeRisi at the University of California-San Francisco and Dr. Dennis Kyle, Distinguished University Health Professor in the College of Public Health at USF.

Dennis Kyle Lab 2

Dennis E. Kyle, PhD

One of the most exciting developments about the new drug candidate is its ability to rapidly kill the malaria parasite. The studies demonstrated an immediate effect of the drug and death of the parasite within the first seven hours after exposure. Importantly, this drug works by a novel mechanism that interrupts the transport of sodium ions into the parasite.

Remarkably, the drug produced even faster clearance of parasites in blood of infected animals, and the team elucidated the mechanism as a selective induction of red cell death that occurs only in red blood cells infected with the malaria parasite. The rapid action and lack of cross-resistance with the existing antimalarial drugs make this an outstanding new drug candidate, and SJ-733 was recently approved by Medicines for Malaria Venture as a clinical candidate for development.

A large multidisciplinary team was involved in the discovery, development and optimization of the drug candidate, including the Medicines for Malaria Venture, as well as representatives from Columbia University, Australian National University and GSK. The University of South Florida’s efforts on this project were led by postdoctoral research associate Anupam Pradhan, PhD, in the Kyle laboratory. Dr. Pradhan conducted essential studies on in vivo, ex vivo and in vitro efficacy of the drug and helped elucidate the rapid mechanism of clearance of the parasite in the infected animals.

Anupam Pradhan, PhD

Anupam Pradhan, PhD