New Avenue of Treatment for Malaria

A new anti-malarial drug that targets the host instead of the parasite nearly eradicated the disease in infected mice in less than 3 days, according to a new study.

“We showed for the first time that host-targeted therapeutics can be used as an effective treatment to cure malaria-infected patients,” says first study author Zenon Zenonos, PhD, a post-doctoral fellow at the Wellcome Trust Sanger Institute in the UK. “The latter means that instead of targeting the parasite itself, targeting host factors essential for parasite survival can be a robust anti-malarial approach.”
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This strategy has been successfully used to treat other infectious diseases, such as AIDS/HIV, but has never been trialed for malaria before. Caused by infection with the parasite Plasmodium falciparum, malaria is treatable but currently available drugs are harsh and resistance often develops.

In 2011, a group of scientists at the Sanger Institute discovered that all strains of Plasmodium falciparum need a human protein called basigin in order for the parasite to invade red blood cells and move on to the next stage of its life cycle. Based upon this previous research, the team developed a nontoxic anti-basigin drug called Ab-1 that renders the parasite unable to enter the red blood cells, and therefore clears the infection.

“In this case, because the pressure to the parasite is indirect, we believe that is less likely for the parasite to develop resistance to this drug,” Zenonos says. “Another advantage of our approach is that due to the mechanism of action of Ab-1, much lower doses are required than if we were to inactivate the same process by targeting a parasite factor.”

Ab-1 didn’t appear to have any obvious side effects in the mice studied, suggesting that the drug may also be safe and effective in humans.

“Ab-1 could possibly fill a valuable treatment niche for returning travelers infected with multi-drug-resistant parasites,” Zenonos says. “Nevertheless, in the future, we might see Ab-1 becoming a feasible response to malaria in malaria-endemic areas.”

He and his team find it very encouraging that similar antibodies targeting the same receptor as Ab-1 have been successfully used in the clinic to treat certain cancers and graft-versus-host disease in transplant patients.

Zenonos and colleagues would like to test Ab-1 in humans at some stage in the future. “There are some discussions now with some collaborators on how to proceed but nothing has been decided yet,” he says.

—Colleen Mullarkey

Reference

Zenonos ZA, Dummler SK, Müller-Sienerth N, Chen J, Preiser PR, Rayner JC, et al. Basigin is a druggable target for host-oriented antimalarial interventions. J Exp Med. 20 July 2015. [Epub ahead of print].