MMV and partners have completed the first-ever comparative analysis of all currently available and in-development antimalarials in terms of the steps they target in the parasite's lifecycle. This information provides the missing pieces of the puzzle needed to develop future medicines able to block transmission of the parasite from person to person.
Current medicines mostly target the malaria parasite at the blood stage in its lifecycle because this is the step that leads to clinical symptoms. To be able to block transmission of the parasite, however, we need to be able to kill the parasite at multiple points in its lifecycle, namely the sexual and vector (mosquito) stages.
The research teams from Imperial College London, Genomics Institute of the Novartis Research Foundation, Swiss TPH, University of Basel, Scripps Research Institute and Medicines for Malaria Venture were able to reproduce the complex biology of the malaria parasite throughout its lifecycle, in the laboratory. This then allowed them to test the activity of 50 anti-infective molecules (the vast majority being available and in-development antimalarials) against each 'laboratory-produced step' to determine exactly where they act.
The research revealed a number of interesting findings. Specifically, some already available antimalarials, such as pyronaridine and atovaquone, can target the liver and sexual stages of the parasite in addition to the blood stage. The endoperoxide OZ439, currently in Phase II clinical trials, and a new 8-aminoquinoline, NPC-1161B, also demonstrated transmission-blocking potential.
"These specific findings will be critical in guiding the selection and combination of next-generation molecules to succeed artemisinin combination therapy and will support the drive to eradicate malaria," said Tim Wells, CSO of MMV, "while the complete data provides us with a benchmark against which to assess any newly discovered molecules."
The original research article entitled: 'The Activities of Current Antimalarial Drugs on the Life Cycle Stages of Plasmodium: A Comparative Study with Human and Rodent Parasites', can be accessed free of charge on the PLoS Medicine website.
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PLoS Medicine