Malaria is a disease that develops when a mosquito infected with a Plasmodium parasite bites a person. Once it gets into the bloodstream, the parasite invades and lives in the new host’s red blood cells. This deadly disease still claims more than half a million lives each year. A new study suggests that a promising new anti-malarial compound tricks the immune system to rapidly destroy red blood cells infected with the parasite without damaging healthy cells.
The compound was developed from a molecule identified in a research from St. Jude Children’s Research Hospital. Laboratory evidence suggests that the compound’s speed and mode of action work together to slow and suppress development of drug resistant parasites. According to researchers, the compound called (+)-SJ733 employs a novel mechanism to kill the malaria parasite. In a mouse model of malaria, a single dose of (+) -SJ733 killed 80 percent of malaria parasites withing 24 hours. After 48 hours, the parasite was no longer detectable.
“The data suggests that compounds targeting ATP4 induce physical changes in the infected red blood cells that allow the immune system or erythrocyte quality control mechanisms to recognize and rapidly eliminate infected cells,” said co-author Joseph DeRisi, a Howard Hughes Medical Institute Investigator. “The rapid clearance response depends on the presence of both the parasite and the investigational drug. That is important because it leaves uninfected red blood cells, also known as erythrocytes, unharmed,” he added.
The team’s work also incorporated the study of another set of anti-malarial compounds called spiroindolones. The drugs include NITD246, a compound that has been tested for anti-malaria properties in clinical trials and also focuses on impacting activity of the ATP4 protein. The researchers observed that these drugs had the same effect as (+) –SJ733 on the infected red blood cells.
Planning is underway to move the compound from laboratory into the clinical trials in adults. Corresponding author Dr. R. Kiplin Guy, chairman of the St. Jude Department of Chemical Biology and Therapeutics, says, “Our goal is to develop an affordable, fast-acting combination therapy that cures malaria with a single dose.” Grants from the National Institute of Health, Medicines for Malaria Venture, Australian National Health and Medical Research Council, and the Howard Hughes Medical Institute helped fund the study.