US scientists have discovered the process in which malaria parasites attack the human body, paving the way for a new oral medication – sotrastaurin – to treat the infection.
Researchers from the University of Pennsylvania and John Hopkins University have identified the cell signalling pathway used by Plasmodium falciparum and Toxoplasma gondii parasites to escape from and destroy their host cells and infect new cells.
They found that when these parasites enter the blood stream, they take up residence inside the membrane of a red blood cell and reproduce for about 48 hours before bursting out and infecting new host cells.
Leader of the study and assistant professor of Pharmacology at the University of Pennsylvania Doron Greenbaum explained, "We found an entire signalling pathway in the human host cell that the parasite engages, starting from a G-protein-coupled receptor that the parasite uses to dismantle the cytoskeleton of the host cell, causing it to collapse."
"There’s a complex series of proteins in this signalling cascade. One of the key proteins is protein kinase C [PKC]. We found a tremendous amount of biological validation for the existence and use of this pathway in both parasitic organisms."
The discovery of this protein pathway may lead to sotrastaurin, which is currently undergoing clinical trials for various indications including transplant rejection and treatment of psoriasis, being used to treat malaria.
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Sotrastaurin, a PKC inhibitor, was shown to block P. falciparum and T. gondii from interaction with PKC, an enzyme which contributes to the loss of protein adducin from the host cell, causing them to collapse.
In the study, involving mice, sotrastaurin administration also resulted in a significant decrease in parasitemia and increased survival rates against Plasmodium berghei ANKA, a deadly strain of malaria.
"We’ve piggybacked this line of research onto a drug class that’s already vetted," says Greenbaum. "We’re quite excited about that. We’ve found a compound that’s already been used in trials in humans and is deemed safe."
Image: Malaria parasites take residence in red blood cells and quickly reproduce. Photo courtesy of FreeDigitalPhotos.net.