Making a Good Drug Even Better

Artemisinin-combination therapy (ACT) is the first choice for countries experiencing resistance to traditional antimalarials.

But recent reports that artemisinin resistance might be appearing along the Thai-Cambodia border are worrying public health experts.

Gary Posner, however, who began synthesizing artemisinin derivatives in the early 1990s, declines to use the term “resistance” quite yet. Posner, PhD, a Chemistry professor in the Johns Hopkins School of Arts and Sciences and a faculty member of the Johns Hopkins Malaria Research Institute, suspects that the Cambodian cases indicate delayed drug “clearance.” The parasite still succumbs to the drug but is acquiring the capacity to survive in its presence for longer, perhaps by entering a dormancy stage.

That’s still a problem: The longer parasites linger in the bloodstream, the more chance they have of spreading the infection. So Posner is designing new artemisinin derivatives. Instead of the six-dose regimen required in current ACT, his new artemisinin derivatives involve just a single dose. For malaria-stricken people in developing countries, “adherence is a big problem,” explains Posner. Patients often take a first dose of a drug but may not take the following doses—ripe conditions for drug resistance.

A single-dose treatment would reduce that risk, and possibly at a fraction of the current cost for ACT.

Last year, Posner, along with Theresa Shapiro, professor of Pharmacology and Molecular Sciences at the Johns Hopkins School of Medicine, and their colleagues reported that a single oral dose of an artemisinin derivative, given in combination with the malaria drug mefloquine, cured malaria-infected mice.

If further funding becomes available, says Posner, he plans to test some of his compounds in monkeys, the next step prior to human testing.