Screening effort turns up multiple potential anti-malaria compounds

National Institute of Allergy and Infectious Diseases
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Screening effort turns up multiple potential anti-malaria compounds

Possible resistance-proof drug pairs found by NIH scientists

 

Bethesda, Md., Thurs, Aug. 4, 2011 - Numerous potential anti-malarial candidate drugs have been uncovered by investigators from the National Human Genome Research Institute (NHGRI) and the National Institute of Allergy and Infectious Diseases (NIAID), both parts of the National Institutes of Health (NIH). The study was published in the August 4 online issue of the journal Science.

Researchers at the NIH Chemical Genomics Center, administered by NHGRI, used robotic, ultra-high-throughput screening technology to test more than 2,800 chemical compounds for activity against 61 genetically diverse strains of lab-grown malaria parasites. They found 32 compounds that were highly effective at killing at least 45 of the 61 strains. Ten of these compounds had not previously been reported to have anti-malarial action, and seven were more active at lower concentrations than artemisinin, a widely used malaria drug. All the screened compounds are already registered as safe or approved for use in humans or animals, although not necessarily for use against malaria. The most promising compounds revealed in the new screen may thus face a shorter path than usual to development into anti-malarial drugs.

Scientists from NIAID's Laboratory of Malaria and Vector Research also determined that just three parasite genes - the same three genes that confer resistance to currently used malaria drugs - were associated with resistance to many of the screened compounds. This suggests that the malaria parasite has a limited number of ways to develop resistance following exposure to drugs. In theory, if drug combinations could be devised to target activity of all three resistance genes simultaneously, the parasite could be disarmed.

The research provides a wealth of leads for scientists seeking to combine new or existing compounds into better multi-drug regimens against malaria. For example, the team identified dozens of compounds that act in a manner similar to artemisinin. Combining drugs that act similarly could yield treatment strategies that work better or require fewer doses.

Because malaria parasites can have a single genetic mutation that confers resistance to one drug while simultaneously increasing sensitivity to another drug, the investigators also looked for pairs of compounds with complementary activities. If used together, such complementary drug pairs could slow the emergence of drug resistance in parasites, because the parasite with the mutation - which does not respond well to one compound - would be killed by the other compound to which it has enhanced susceptibility conferred by the mutation. In this regard, the team found many compounds that killed strains of parasites resistant to a standard malaria drug, chloroquine. Since chloroquine-resistant parasites are widespread in many parts of the world, further studies of compounds with complementary activity could lead to new combination treatments for these drug-resistant parasites, the scientists write.

Article

Yuan J, et al. Chemical genomic profiling for antimalarial therapies, response signatures and molecular targets. Science, Aug.4, 2011. [PubMed]

Contact

To schedule interviews with Dr. Su or Dr. Wellems, contact the NIAID Office of Communications, (301) 402-1663 or niaidnews@niaid.nih.gov

To schedule interviews with Dr. Austin, contact Raymond MacDougall at 301-402-0911 or macdougallr@mail.nih.gov

NIAID conducts and supports research-at NIH, throughout the United States, and worldwide-to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID website at www.niaid.nih.gov.

NHGRI is one of the 27 institutes and centers at the NIH, an agency of the Department of Health and Human Services. The NHGRI Division of Intramural Research develops and implements technology to understand, diagnose and treat genomic and genetic diseases. Additional information about NHGRI can be found at its website, www.genome.gov.

About the National Institutes of Health (NIH): NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov