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Body + BrainBody & Brain

One-Dose Malaria Cure Shows Promise in Animal Trials

ByTim De ChantNOVA NextNOVA Next

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This drug is one-in-100,000.

On a quest to find a new malaria treatment, an international team of dozens of researchers sifted through around 100,000 compounds. They ended up finding one truly novel drug, and it has a lot of promise. In fact, it was so novel that they had to devise a clever experiment to determine exactly how it worked.

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Called BRD7929, the drug is radically different from other treatments for which P. falciparum is evolving resistance, giving it potentially added potency. In trials, it cleared the parasite from specially bred mice with just one dose.

late-stages-malaria

Should such a powerful drug work safely in humans, it could drastically reduce malaria rates. As with any new drug candidate, there are many more tests needed before it can be widely prescribed. But given that this was tested in mice grafted with human liver cells, the drug’s activity should more closely mimic that seen in humans than a typical mouse model.

Initially, the researchers’ fishing expedition turned up four different compounds. John Timmer, writing for Ars Technica, explains how they whittled the list down to one:

Each of the drugs was tested for its ability to slow down parasite growth in cultured red blood cells. Four different sets of related chemicals came out of the screen. Three of them bound to proteins that are already targets of known drugs. So, while they could end up being useful, they’re not anything new.

The fourth chemical, however, was something entirely new, and nobody knew what it was sticking to. The structure of the chemical doesn’t provide many clues, given it’s got a large series of rings, some of them with unusual numbers of carbon atoms. So to figure out how it worked, the team intentionally used low doses of the drug for a few months to allow Plasmodium to evolve resistance to it. Once the parasite survived the drug, they sequenced its genome, looking for changes that could be associated with the resistance.

The new drug disrupts the malaria parasite’s ability to produce certain proteins it needs to live. After tweaking the originally isolated compound, the researchers were able to produce a pill that they could give to malaria-infected mice, an important development given that pill forms of drugs are far easier to distribute and administer than injections, for example.

That the drug only needs one dose to clear P. falciparum from a patient’s body is also key. Malaria resistance can evolve when patients don’t take the full dose of their medication.

Photo credit: G.H. Nicholson/U.S. Department of Health, Education, and Welfare