Salt pumps: A chink in the malaria parasite’s armour

Link to mechanism of action of new antimalarial compound
21 February 2013

© iStockphoto.com/David Pinn

Australian National University (ANU) researchers Natalie Spillman and Professor Kiaran Kirk have found that tiny sodium pumps are critical to the survival of the deadly malaria parasite, Plasmodium falciparum. Spillman found that the parasite controls its salt balance by using the pump, called Plasmodium falciparum ATP4, to expel salt from its “body”.

Spillman and Kirk were informed of NITD 609, a highly promising new antimalarial compound of the spiroindolone class. NITD 609 is being developed by Novartis Institute of Tropical Diseases and Medicines for Malaria Venture with significant support from the Wellcome Trust, the Bill and Melinda Gates Foundation, UK DFID, the President’s Malaria Initiative, USAID, the Swiss Agency for Development and Cooperation, and other donors committed to the elimination and eradication of malaria.

The ANU scientists investigated the effect of this potential drug and discovered that the spiroindolones killed parasites by effectively blocking the salt pump, thus allowing sodium levels in the parasite to rise to toxic levels. Their findings have been recently published in Cell Host & Microbe.

The identification of the spiroindolone’s mechanism of action on the malaria parasite has important implications on the R&D of new antimalarial medicines. The hunt will now be on for other medicines that act in the same way.

The compound NITD 609, meanwhile, will have to go through rigorous testing in humans to prove that it is well-tolerated and efficacious before it can be registered in a combination medicine for P.falciparum malaria.