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The newspaper of The Johns Hopkins University August 7, 2006 | Vol. 35 No. 41
Antihistamine Identified As Potential Antimalarial Drug

By Tim Parsons
School of Public Health

The allergy medication astemizole could have another life as a potential treatment for malaria, according to a study conducted by researchers from the Johns Hopkins Bloomberg School of Public Health and the Johns Hopkins School of Medicine. The study, largely funded by the Johns Hopkins Malaria Research Institute, determined that in a test tube the antihistamine killed the parasite Plasmodium falciparum, which causes malaria in humans, including strains that were resistant to traditional malaria therapies. The drug also was shown to be effective in mouse models. The findings are published in the July 2 advanced online edition of Nature Chemical Biology.

"Time and money are major roadblocks when it comes to developing new drugs for the treatment of neglected diseases like malaria," said senior study author David Sullivan, an associate professor with the Malaria Research Institute and the Bloomberg School's W. Harry Feinstone Department of Molecular Microbiology and Immunology. "Astemizole is promising as an antimalarial but still needs to be evaluated for effectiveness as an antimalarial in humans."

For the study, Sullivan and colleagues Curtis Chong and Jun Liu, both of the School of Medicine's Department of Pharmacology, first assembled the Johns Hopkins Clinical Compound Library, a collection of 2,687 drugs. Seventy percent of the compounds are approved by the U.S. Food and Drug Administration and the other 30 percent by regulatory agencies in other countries. Screening the drugs for their effectiveness in killing the malaria-causing parasite, the researchers found that astemizole was one of the more promising.

The researchers then gave astemizole, along with the drug's major human metabolite, desmethylastemizol, to mice infected with Plasmodium. They measured 80 percent reduction in parasite counts with moderate doses of the drug in chloroquine-sensitive mice and 40 percent reductions in chloroquine-resistant mice. Higher doses completely eliminated Plasmodium infection.

Astemizole was voluntarily withdrawn from the U.S. and European markets in 1999, after 15 years of use, when sales became sluggish following warnings about the drug's safety and the introduction of newer antihistamines. The drug was reported to cause rare but life-threatening heart arrhythmias when patients took an overdose or took it with drugs that affected its metabolism. However, arrhythmias are also reported with existing malaria drugs and with other antihistamines now sold over the counter. Astemizole is currently used in 30 countries, including Cambodia, Thailand and Vietnam, where malaria is endemic.

Human studies are planned to evaluate the effectiveness of astemizole directly in asymptomatic malaria patients, a process that will be accelerated by the fact that the medication has been through an approval process. The researchers hope next to validate this drug class for use in combination with existing malaria drugs, such as artemisinin or the quinolines.

The Johns Hopkins Clinical Compound Library will now be available to screen existing drugs for new uses for diseases affecting the developing world. "This line of research can be applied to many neglected diseases," said Chong, the lead author of the study.

The study was written by Chong, Xiaochun Chen, Lirong Shi, Liu and Sullivan.

In addition to the Johns Hopkins Malaria Research Institute, the research was supported by the Johns Hopkins University Fund for Medical Discovery and Department of Pharmacology, and the Keck Foundation.


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