Compound kills off malaria by making infected cells appear as aging red blood cells
Though recent research has given hope to the anti-malaria cause, the deadly disease still claims more than half a million lives each year. A study led by researchers at St Jude Children's Research Hospital in Memphis suggests that a certain compound results in the body's immune system treating malaria-infected cells the same way it does aging red blood cells, leading to the parasite becoming undetectable in mice within 48 hours.
The researchers discovered that by targeting a specific protein in the malaria parasite known as ATP4, they could affect change in the infected red blood cells. The reason for this is ATP4 has the important function of regulating the parasite's sodium balance.
Using a compound called (+)-SJ733, which has been established as an anti-malarial drug candidate in previous research, the scientists were able to inhibit the activity of ATP4. This caused infected cells to shrink, become more rigid and change in shape, all characteristics of aging red blood cells.
These symptoms led the body's immune system to identify the cells for destruction, while leaving the healthy cells untouched. In mice, the (+)-SJ733 compound killed off 80 percent of malaria parasites within 24 hours, while after 48 hours it was undetectable.
"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," says R. Kiplin Guy, Ph.D. and chair of the St. Jude Department of Chemical Biology and Therapeutics.
The team's work also incorporated the study of another set of antimalarial 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.
The findings of the study also indicate that compounds such as these could hinder the development of drug-resistant malaria strains, a factor the researchers say has damaged previous efforts to tackle malaria.
Plans are now in place to test (+)-SJ733 in human trials.
The team's findings were published in the Proceedings of the National Academy of Sciences (PNAS).