New Drug for Malaria?

A new antimalarial drug candidate has the potential to be a single-dose treatment, according to a new report from researchers at Columbia University Vagelos College of Physicians and Surgeons and colleagues at the nonprofit Medicines for Malaria Venture.

Though malaria infections and deaths declined sharply from 2000 to 2015, the disease still infects more than 2 million people and results in more than 400,000 deaths—mostly children under age 5—each year.

Columbia scientists James Murithi, PhD, and David Fidock, PhD

James Murithi (left) and David Fidock

Evidence shows that malarial parasites are becoming increasingly resistant to front-line drugs, threatening to erase hard-earned progress in fighting the disease.

“New drugs are needed to sustain the progress against malaria, and what’s particularly exciting about this compound is that a single dose may be enough for a cure,” says James M. Murithi, PhD, who conducted the research during graduate school at Columbia University in the laboratory of David Fidock, PhD, the C.S. Hamish Young Professor of Microbiology & Immunology and of Medical Sciences. Their findings were published in Science Translational Medicine.

“A single dose would tremendously help compliance,” Murithi says. “Existing first-line drugs must be taken several times a day for a number of days, and many people do not complete the full course of treatment.”

The new compound also has other promising features. Laboratory experiments suggest parasites cannot easily develop resistance to the drug, as has happened to current antimalarial agents. And the new compound also appears to be effective against all strains of the parasite. The compound is in clinical trials in Australia.

Though it’s not fully known how it works, the compound appears to clear P. falciparum parasites from infected blood cells by interfering with lipid-associated transport of essential intracellular molecules, a mode of action that has not been seen before. This mode of action enables the drug to escape existing mechanisms of resistance.

Finding new antimalarials is even more urgent as the climate changes, Murithi and Fidock say.

“Warmer and wetter weather is favorable to the mosquitoes that carry malarial parasites, so climate change will most assuredly increase transmission in tropical areas of the world,” Fidock says.

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The compound was originally discovered by Sanofi in screens against Plasmodium falciparum cultured asexual blood stage parasites. 

The study, titled “The antimalarial MMV688533 provides potential for single-dose cures with a high barrier to Plasmodium falciparum parasite resistance,” was published July 21 in Science Translational Medicine. 

Funding for this work was provided by the Medicines for Malaria Venture; an in-kind contribution from Sanofi; the U.S. National Institutes of Health (grants R01 AI124678 and R01 AI109023); the Bill & Melinda Gates Foundation (OPP1201387); the U.S. Department of Defense (W81XWH-19-1-0086); a Human Frontier Science Program Long-term Postdoctoral Fellowship (LT000976/2016-L); and a Wellcome Trust Senior Fellowship in Clinical Science (200909). 

All authors: James M. Murithi (Columbia), Cécile Pascal (Sanofi), Jade Bath (Columbia), Xavier Boulenc (Sanofi), Nina  F. Gnädig (Columbia), Charisse Flerida A. Pasaje (Massachusetts Institute of Technology), Kelly Rubiano (Columbia), Tomas Yeo (Columbia), Sachel Mok (Columbia), Sylvie Klieber (Sanofi), Paul Desert (Sanofi), María Belén Jiménez-Díaz (the Art of Discovery, Bizkaia, Spain), Jutta Marfurt (Charles Darwin University, Australia), Mélanie Rouillier (Medicines for Malaria Venture), Mohammed H. Cherkaoui-Rbati (Medicines for Malaria Venture), Nathalie Gobeau (Medicines for Malaria Venture), Sergio Wittlin (Swiss Tropical and Public Health Institute and Universität Basel), Anne-Catrin Uhlemann (Columbia), Ric N. Price (Charles Darwin University, University of Oxford, and Mahidol University, Thailand), Grennady Wirjanata (Charles Darwin University), Rintis Noviyanti (Eijkman Institute for Molecular Biology, Jakarta, Indonesia), Patrick Tumwebaze (Infectious Diseases Research Collaboration, Kampala, Uganda), Roland A. Cooper (Dominican University of California), Philip J. Rosenthal (University of California, San Francisco), Laura M. Sanz (GSK), Francisco Javier Gamo (GSK), Jayan Joseph (Syngene International, India), Shivendra Singh (Syngene International), Sridevi Bashyam (Syngene International), Jean Michel Augereau (Sanofi), Elie Giraud (Sanofi), Tanguy Bozec (Sanofi), Thierry Vermat (Sanofi), Gilles Tuffal (Sanofi), Jean-Michel Guillon (Sanofi), Jérôme Menegotto (Sanofi), Laurent Sallé (Sanofi), Guillaume Louit (Sanofi), Marie-José Cabanis (Sanofi), Marie Françoise Nicolas (Sanofi), Michel Doubovetzky (Sanofi), Rita Merino (Sanofi), Nadir Bessila (Sanofi), Iñigo Angulo-Barturen (the Art of Discovery), Delphine Baud (Medicines for Malaria Venture), Lidiya Bebrevska (Medicines for Malaria Venture), Fanny Escudié (Medicines for Malaria Venture), Jacquin C. Niles (Massachusetts Institute of Technology), Benjamin Blasco (Medicines for Malaria Venture), Simon Campbell (Medicines for Malaria Venture), Gilles Courtemanche (Bioaster, France), Laurent Fraisse (Sanofi), Alain Pellet (Sanofi), David A. Fidock (Columbia), Didier Leroy (Medicines for Malaria Venture). 

The Columbia authors declare no competing interests.