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Gates Foundation Grant to Study Malaria Drug Resistance


Professor Jean Chmielewski
Purdue University Alice Watson Kramer Distinguished Professor Organic Chemistry/Chemical Biology

Purdue University researchers may have a way to renew once successful malaria treatments and have them work against drug-resistant strains.

The Bill & Melinda Gates Foundation has selected the Purdue project, led by chemistry professors Christine Hrycyna and Jean Chmielewski, for a Grand Challenges Explorations grant. The project was one of 78 selected from almost 2,700 proposals.

Almost half of the world's population is at risk of malaria, and every 30 seconds a child dies from the disease, according to the World Health Organization.

"We hope to create a technique that could lead to inexpensive and readily available antimalarial drugs to battle this devastating disease," Hrycyna said. "By finding a new way to use previously successful drugs that are known to be safe and effective, we have a head start that reduces the cost and lets us get the treatment to people faster."

Malaria is an often-fatal disease caused by plasmodium parasites that

multiply in red blood cells and are spread from person to person through the bites of infected mosquitoes. In the past century the parasite has developed widespread resistance to the drugs available to treat the disease.

Professor Christine Hrycyna
Purdue University Professor Biochemistry

This resistance is due to reduced accumulation of the drugs in the digestive system of the parasite through an adaptation that allows the parasite to push the drugs out of its system, Chmielewski said.

"We've developed a way to block the main mechanism that pushes drugs out of the digestive vacuole of the parasite before they have a chance to work," Chmielewski said. "It's actually a fairly simple redesign of existing drugs that shows promise in increasing the accumulation of drugs within the parasite."

The team designed a way to link pairs of molecules of traditional antimalarial drugs that enable them to effectively block theP. falciparumresistance transporters. Once this back door out of the digestive system is blocked, the drugs build up in the system and have time to do their work. The molecular pairs are linked with a "traceless tether" that breaks down in the digestive vacuole, reverting the compound back into the original antimalarial drug, she said.

The team has had early success using the technique on the antimalarial drug quinine, and the experimental results suggest that the redesigned molecules may be more potent and effective than the original drugs against drug-resistant malaria, Hrycyna said.

The $100,000 grant from the Bill & Melinda Gates Foundation supports further evaluation with different antimalarial drugs and work to improve understanding of the role of transporters in resistance.

Hrycyna and Chmielewski 's project was selected by the Gates Foundation in the fourth funding round of Grand Challenges Explorations, an initiative to foster creative projects that show great promise to improve the health of people in the developing world. The grants were provided to scientists in 18 countries on six continents.

"The winners of these grants show the bold thinking we need to tackle some of the world's greatest health challenges," said Dr. Tachi Yamada, president of the Gates Foundation's Global Health Program. "I'm excited about their ideas and look forward to seeing some of these exploratory projects turn into life-saving breakthroughs."

Grand Challenges Explorations is a five-year, $100 million initiative of the Gates Foundation to promote innovation in global health research. The receipt of this initial grant makes Hrycyna and Chmielewski eligible for additional funding of up to $1 million from the Bill & Melinda Gates Foundation.

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