Researchers demonstrated that a compound can trick the immune system into killing red blood cells containing the malaria parasite without damaging healthy cells.
The compound, (+)-SJ733, was developed from a previously-identified molecule that has led to number of malaria therapy breakthroughs, St. Jude Children's Research Hospital reported. In this study, researchers found that (+)-SJ733 kills malaria parasites by eliminating infected blood cells. A single dose of the molecule proved to be able to eradicate 80 percent of the malaria parasites in a mouse model within 24 hours; after 48 hours the parasites were undetectable in the subjects.
"Our goal is to develop an affordable, fast-acting combination therapy that cures malaria with a single dose," said corresponding author R. Kiplin Guy, chair of the St. Jude Department of Chemical Biology and Therapeutics. "These results indicate that SJ733 and other compounds that act in a similar fashion are highly attractive additions to the global malaria eradication campaign, which would mean so much for the world's children, who are central to the mission of St. Jude."
Using genome sequencing of Plasmodium falciparum (the deadliest malaria parasite), researchers found that (+)-SJ733 disrupted activity of the ATP4 protein, which ensures an adequate balance of sodium. Researchers also found that inhibiting ATP4 triggered changes in the malaria-infected red blood cells that made them easier for the immune system to identify. Another class of antimalarial compounds were found to trigger the same changes in red blood cells infected with the malaria parasite, according to Science Daily.
"The data suggest 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 and chair of the University of California, San Francisco Department of Biochemistry and Biophysics.
"This 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."
The findings were published in a recent edition of the Proceedings of the National Academy of Sciences (PNAS).
