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NIH Investigators Discover New Targets for Anti-Malarial Drugs

Almost 430,000 individuals succumbed to malaria infection in 2015.

Investigators on a new study from the National Institutes of Health (NIH) have identified new targets for anti-malaria drugs, welcome news as the deadly infection continues to plague countries around the world.

Responsible for approximately 212 million cases in 2015, malaria causes fever, chills, and flu-like illness. If untreated, the mosquito-borne parasitic disease can lead to death. In fact, almost 430,000 individuals succumbed to the infection in 2015. Most of these individuals lived in sub-Saharan Africa or South Asia. As such, the World Health Organization issued the Global Vector Control Response 2017—2030 (GVCR) strategy to strengthen vector control worldwide and better enable response to the disease.

The situation is dire, though, as, according to the NIH, the parasite that causes most malaria deaths, Plasmodium falciparum, has developed resistance to drugs to treat the infection in 5 countries in Southeast Asia.

Therefore, researchers from the NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and the Washington University School of Medicine in Saint Louis, and led by Joshua Zimmerberg, MD, PhD, head of NICHD’s Section on Integrative Biophysics, sought to learn more about the proteins that malaria’s deadliest parasite needs for metabolic and other processes. Specifically, the investigators “sought to uncover the role of plasmepsins IX and X,” according to the NIH.

After creating malaria parasites that lacked these 2 plasmepsin proteins, the investigators compared the actions of the parasites with those that had the proteins. They found that one of the proteins, plasmepsin IX, was found inside rhoptries, which are “specialized cell structures inside the parasite [that] help it invade red blood cells,” according to the NIH. In the parasites that were lacking this protein, the rhoptries were defective.

Plasmepsin X proteins were found in exonemes, which are, “small vesicles (balloon-like structures) that help malaria parasites exit infected cells,” according to the NIH. In addition, the plasmepsin X proteins were found to process an important protein, SUB1. Those parasites that were lacking plasmepsin X were not able to process SUB1, nor were they able to infect red blood cells and leave those cells after they multiplied.

Armed with this new knowledge, the investigators were able to identify 3 experimental malaria drugs that may target plasmepsin X. The NIH mentioned one of these drugs, CWHM-117, which “has already been tested in a mouse model of malaria.” Knowing more about the role of plasmepsin X may help researchers to modify CWHM-117 to render it more effective. In addition, the NIH states that “parasites lacking the plasmepsins could potentially be used to screen candidate drugs to identify additional anti-malaria compounds.”

New antimalarial drugs can be a game-changer in the fight against this deadly disease. Recently, Jeremy Burrows, DPhil, MA, Vice President, Head of Discovery, Medicines for Malaria Venture, Switzerland, sat down with Contagion® to explain why.

The NIH study was conducted with funding provided by the National Institute of Allergy and Infectious Diseases, the National Heart, Lung, and Blood Institute, and the National Institute of General Medical Sciences.

The full study is published in the journal, Science.