The study showed that blocking a protein the malaria parasite needs to invade blood cells wiped out the disease in infected mice in 3 days.
For example, in Southeast Asia, one of the current front-line antimalaria drugs - artemisinin - is now largely ineffective.
Researchers are in a race against time to find a solution before the resistant strains spread to other malaria-endemic areas, including Africa - a region that accounts for 90% of global malaria deaths.
Now, a research team shows that finding targets in the host as opposed to the parasite could be a new way to slow down, if not overcome, the problem of drug resistance in malaria.
To survive in the host body, the malaria parasite needs oxygen and nutrients. Such a plentiful environment is supplied by red blood cells. However, the parasite cannot enter the cells without help from a protein that "opens the door" for them. This protein is a receptor called basigin.
In The Journal of Experimental Medicine, Dr. Zenon Zenonos, of the Wellcome Trust Sanger Institute in the UK, and colleagues describe how blocking basigin prevents the most deadly malaria parasite, Plasmodium falciparum, from completing its life cycle.
In their study, they show how a treatment that disables the blood protein wipes out malaria in infected humanized mice in under 3 days.
Blocking host protein interaction prevents malaria parasite from completing life cycle
Dr. Zenonos, who is first author of the study, explains how their "counter-intuitive approach" leaves the malaria parasite powerless:
"If the parasite can't bind to the surface of our red blood cells and invade, it can't reach the next stage in its life cycle, so it dies. There's nothing the parasite can do to get round it, as the interaction is absolutely essential for infection to occur."
In order to bind to basigin and enter red blood cells, the malaria parasite needs another protein called PfRH5 (think of PfRH5 as the "key" and basigin as the "lock"). In their study, the team blocked the interaction between PfRH5 and basigin.
Corresponding author Dr. Gavin Wright, also of the Wellcome Trust Sanger Institute, explains that when they discovered the PfRH5-basigin interaction in 2011, they had an idea it might be a weak spot in the malaria parasite's armour. The question that then remained was how to exploit it. He explains:
"Using PfRH5 in a vaccine is one approach, but we were also interested to see if we could disrupt the interaction in the opposite direction rather than by conventionally targeting the parasite. This has significant advantages in preventing the ability of the parasite to develop resistance."
The team developed an antibody to target basigin and tested it in humanized mice that have had most of their immune cells and blood cells replaced by human equivalents.
They found that within 72 hours of administering low doses of the basigin-targeting antibody to mice infected with malaria, the infection was no longer detectable. Also, they saw no toxic side effects in the treated mice.
Currently, the cost of producing and administering such antibodies is high, but the researchers hope advances in technology will bring the costs down.
In the meantime, the study may well spur others to look at host-side targets as a way to tackle the growing problem of drug resistance in malaria.
Medical News Today recently reported another study that shows how attacking the malaria parasite in a different way could also address the problem of drug resistance. The researchers found a compound that prevents the malaria parasite from making the building blocks it needs to generate its genetic material during replication.