UIC researchers develop new drug to attack an enduring killer

Malaria is an ancient disease, dating back to 3000-4000 B.C., according to genetic evidence. Two hundred and fifty million people are infected each year, and 610,000 of those cases are fatal.

UIC researchers have developed a new antimalarial drug designed to thwart even the most drug-resistant forms of the infection. Early testing in mice killed malaria parasites in just one dose.

"Malaria is one of the biggest killers worldwide, and most of its victims are children in sub-Saharan Africa aged 5 years or less," said lead investigator Paul Carlier, the Hans W. Vahlteich Chair in Medicinal Chemistry in the Retzky College of Pharmacy. "This infection limits human flourishing in a very important part of the world. It's a health equity issue."

"Because malaria is an ancient disease, people have been using different substances to treat it. But the problem is, parasites become resistant to existing medicines. So there's a constant arms race taking place where we're constantly developing new drugs to tackle resistance," Carlier said.

Some malaria drugs make the disease dormant: Surface-level symptoms dissipate but the parasite remains. Others require multiple rounds to work well.

"Imagine your child is sick and you need to walk for days to get medicine," Carlier said. "The nurse prescribes multiple doses over three days. After two days, your child is feeling better, so you decide to share your remaining doses with your neighbor's sick child.

"This is a wonderful instinct, but if your child doesn't finish the full course, the infection will likely come back."

Thus far in testing, Carlier's new oral antimalarial is irresistible, meaning parasites cannot become resistant to it. It kills dormant parasites and works well in a single dose. In this study, the drug successfully cured mice infected with Plasmodium yoelii, a parasite that mirrors how malaria behaves in humans.

Carlier said drug discovery is the most direct, effective way to target the mosquito-borne illness.

"For many years, we worked on mosquito-directed interventions," he said, in other words, controlling the proliferation of mosquitos. "Those are great for prevention, but we are interested in treating people. Vaccines are increasingly important for malaria, but still not very widely used. And a vaccine can't help you if you've already got the disease."

Carlier has been developing drugs to target malaria for 20 years. Since 2022 he has directed UICentre, the university's campuswide drug discovery initiative. His team in the department of pharmaceutical sciences has filed a patent application for the new antimalaria drug and is seeking continued funding from the National Institutes of Health to begin the next phase of studies.

"Our goals are to improve potency, reduce side effects and reduce the necessary dosage," he said. "We are on the 10-yard line, but we're not in the end zone yet."

Bo Zhou, a PhD candidate in the department of pharmaceutical sciences of the Retzky College of Pharmacy, is the first author of this study. Collaborating institutions are the University of Georgia, Molsoft, Portland State University, the University of Dundee and Medicines for Malaria Venture in Geneva, Switzerland.

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Jenna Kurtzweil

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drug discovery, malaria