Drug Flags Malaria-Infected Cells For Destruction

The drug, still in its early development stages, could be especially difficult for malaria to evolve defenses against

Malaria, that tricky beast, has become resistant to the medicines that people use to kill it. In decades past, malaria microbes have been seen to evolve resistance to chloroquine and sulfadoxine-pyrimethamine, two popular anti-malaria drugs. This year, doctors in Southeast Asia reported they’re seeing malaria that’s resistant to artemisinin, once considered effective on every strain of malaria everywhere. So the race is on to find the next anti-malarial drug—or drugs.

One experimental drug posted some good news recently. At the end of November, a team reported some good results from testing a chemical called (+)-SJ733 in cells grown in lab and in lab animals, such as rats, mice, and dogs. What makes the study interesting is that the scientists tested one possible way malaria might evolve against (+)-SJ733. They found resistance will likely arise slowly. The team included researchers from the pharmaceutical company GlaxoSmithKline, as well as biologists from universities and research institutes all over the world.

Of course, (+)-SJ733 is at least several years away from an approved drug people can take. It still needs to prove itself safe and effective in people. Meanwhile, to combat drug-resistant malaria infections, doctors are combining existing drugs and instructing their patients to take the drugs for a few days longer, NPR reports.

(+)-SJ733 makes malaria-infected cells look like they’re ready to die.

(+)-SJ733 kills malaria-infected red blood cells in an interesting way. It forces malaria-infected cells to look like they’re ready to die. Cells often naturally prepare to die when they’re old or injured. When it’s time, they undergo a process called apoptosis, breaking down in an orderly fashion that doesn’t harm neighboring cells and that makes their proteins available for re-use by others. So nice, right?

(+)-SJ733 changes malaria-infected cells’ shape and forces them to push to their surfaces special molecules. The molecules flag them as ready for destruction. In lab animals, the immune system recognizes the flags and zooms in to help.

In addition, by conducting a sort of mini-evolution experiment, the researchers determined that malaria microbes could evolve to resist (+)-SJ733 by mutating a gene they have called pfatp4. (I’m not sure how you say that. Pee-fat-pee-four?) However, pfatp4-mutated malaria are not as healthy as normal malaria and don’t reproduce as quickly. That might mean that malaria would have a hard time adapting to any future drug based on (+)-SJ733.

The team published their work in the Proceedings of the National Academy of Sciences.