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NIAID Grantees Add New Candidates to Malaria Drug Pipeline

Photo of P. falciparum
A team of NIAID-supported researchers have identified 172 chemical candidates effective against the malaria parasite P. falciparum.
Credit: CDC / Dr. Mae Melvin

Malaria has been eradicated in the United States since the 1950s, but worldwide, it continues to affect 200-300 million people every year. Recently, NIAID-supported researchers, coordinated by a group at St. Jude Children’s Research Hospital, identified 172 candidate chemicals that can be used to develop new antimalarial drugs. Their results were published in the May 20, 2010 issue of the journal Nature.

Plasmodium falciparum, one of the four parasites that cause malaria, is responsible for 880,000 deaths every year. Although treatments already exist, malaria-causing parasites have evolved to become resistant to most of these drugs and are now able to fight them off, making them ineffective.

This growing problem of antimicrobial resistance has driven researchers to look for new chemical treatments. In recent years, scientists’ understanding of P. falciparum and its genetics has grown, but the current pipeline of antimalarial compounds does not fully exploit this knowledge. “This project is an impressive collaboration between many academic and industry researchers and has led to an explosion in the number of potential drugs against malaria, which offers an arsenal of potential drugs to combat the threat of drug-resistant malaria,” says Martin John Rogers, a program officer in NIAID’s Parasitology and International Programs Branch.

In this study, the group used a chemical genetic approach to test the effectiveness of 309,474 chemicals against P. falciparum. The chemicals, chosen to represent a chemically diverse library, went through multiple tests to measure their antimalarial activity. After the series of tests, 172 candidates were found to be promising starting points for drug development.

Most of the 172 candidates were effective specifically against P. falciparum, but some also showed activity against other malaria-causing parasites. Many worked in different ways than existing treatments. An example of a compound with suitable drug-like properties was selected and also found to be effective in a murine mouse malaria model, showing that that these are starting points for further drug development.

In conclusion, say the study authors, “Drug therapy remains a key component in controlling malaria...We expect that these findings will provide novel paths for drug development and hope that making this set of well characterized, non-proprietary lead antimalarials publicly available to the global research community will help to reinvigorate drug discovery for malaria.”

Citation:

Guiguemde WA et alChemical genetics of Plasmodium falciparum. Nature. (465):311-315 (2010).

Additional reference:

Centers for Disease Control and Prevention. Malaria Facts. (February 2010).

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Last Updated August 05, 2010

Last Reviewed July 28, 2010