12:56am Monday 25 September 2017

NIH-Funded Scientists Identify Potential Target for Malaria Drugs

Researchers have identified the protein in malaria-causing Plasmodium parasites that is inhibited by a newly discovered class of anti-malarial compounds known as imidazopyrazines. The protein, phosphatidylinositol 4-kinase (PI4K), is the first

Malaria is transmitted to humans via the bite of a Plasmodium-carrying mosquito.
Credit: CDC/Jim Gathany
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potential malaria drug target shown to be essential to all stages of the Plasmodium life cycle; imidazopyrazines impede its activity throughout this process. Led by Elizabeth Winzeler, Ph.D., of the University of California, San Diego and Novartis Research Foundation, the research was published online today in Nature. The work was supported by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, and other organizations.

When a Plasmodium-carrying mosquito bites a human, it transmits infectious parasites that travel to the liver, where they multiply and mature, and then spread throughout the bloodstream, causing malaria symptoms to develop. Dr. Winzeler and her colleagues administered imidazopyrazines to mice and nonhuman primates infected with Plasmodium and found that the compounds blocked the parasites’ development both in the liver and in the bloodstream stages of infection. They also exposed Plasmodium parasites directly to imidazopyrazines and searched for genetic differences between parasites susceptible to the compounds and those that were resistant. They found that the imidazopyrazine-resistant parasites had mutated versions of the gene that codes for PI4K.

Currently, only one drug, primaquine, has been approved for elimination of liver-stage parasites for the treatment of relapsing malaria. Knowing that PI4K makes Plasmodium parasites susceptible to imidazopyrazines during the liver and bloodstream stages should help researchers optimize these compounds for future clinical testing in humans, the study authors write.

McNamara CW et al. Targeting Plasmodium PI(4)K to eliminate malaria. Nature. DOI: 10.1038/nature12782 (2013).

Martin John Rogers, Ph.D., Program Officer, Parasite Drug Development, in NIAID’s Parasitology and International Programs Branch, is available to discuss the findings.

To schedule interviews, please contact Nalini Padmanabhan, (301) 402-1663, niaidnews@niaid.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 Web site at www.niaid.nih.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.

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