Researchers at MIT have discovered the means of growing their own dormant malaria parasites, granting them the ability to study how it operates, its vulnerabilities, and how it seemingly resurrects itself.
All of this is housed in engineered human liver tissue. With the malaria parasite so housed, scientists are now able to develop and test new drugs to counter it–a traditionally difficult task, as this form of the malaria parasite is resistant to most antimalarial drugs. It essentially hides in the liver after infection and can reawaken months or even years after initial infection, quickly bringing the seemingly recovered back to a malaria decimated state.
As Sangeeta Bhatia, the John and Dorothy Wilson Professor of Health Sciences and Technology and Electrical Engineering and Computer Science, as well as senior author of the study notes, this has been a critical barrier to elimination of malaria. One could kill all the parasites in the blood, and yet it could still bounce back–and once it bounces back, any wandering mosquito could take it and pass it along.
“After 10 years of hard work, we were able to grow the organism, show it had all the functional hallmarks, perform a drug screen against it, and report the first transcriptome of this elusive form. I’m really excited because I believe it will open the door to both the basic biology of dormancy as well as the possibility of better medicines,” Bhatia said.
He was joined in the study by MIT graduate student Nil Gural, who serves as first author.
Currently, only one drug on the market can kill the hypnozoites necessary to eradicate the dormant form of malaria. It’s called primaquine, but unfortunately, it cannot be used on a large scale due to one serious problem: it causes blood cells to rupture in people with an enzyme deficiency.
The findings were published in the Feb. 22 issue of Cell Host and Microbe. In future studies, researchers intend to use single cell RNA-sequencing to determine gene signatures and reveal the pathways that actually lead to hypnozoite activation and deactivation.