![A metabolic enzyme crucial for malarial parasite survival at each stage of infection in humans has been identified. As reported in Nature, an international team […]](/wp-content/uploads/2013/02/NEWSICON2-620x300.png "Enzyme Target to Kill Malaria Parasite")
A metabolic enzyme crucial for malarial parasite survival at each stage of infection in humans has been identified. As reported in Nature, an international team of scientists, including researchers at Columbia University Medical Centre (CUMC), have proposed that drugs targeting this enzyme could provide a novel approach to curing malaria.
Certain strains of the malarial parasite can persist in the liver only to re-trigger the blood-stage infection years later. Although the drug Primaquine can be used to kill the parasite in the liver, it tends to be poor at targeting the blood-stage of infection. Therefore the discovery of the parasitic enzyme, PI(4)K, which is crucial for all life-stages of the parasite, has provided a dramatic advance for the potential treatment and prophylaxis of malaria, a major global killer.
Researchers found PI(4)K by screening over one million drugs against the most lethal form of the malarial parasite. From this screen, they identified a new class of antimalarial compounds, imidazoprazines, capable of killing the parasite at several life-cycle stages. To identify the target of the imidazoprazine compounds, the research group generated imidazoprazine-resistant strains of the parasite and then searched for the genetic changes underlying resistance induction. The gene encoding the PI(4)K enzyme was illuminated, rendering the enzyme the target of the drug compounds.
Importantly, Imidazoprazines have no effect on human cells, thus provide a mechanism for killing malarial parasites without damaging the human host cell. Despite the discovery of this key enzyme in the survival of malarial parasites, we are a way off from developing a clinical drug that targets this pathway. Imidazopyrazines are a good starting point, but require further optimization for a desirable clinical drug. Furthermore, when developed, the drug will likely be used in combination with other antimalarials in order to mitigate potential for drug resistance.
Read more at: http://www.nature.com/nature/journal/vaop/ncurrent/full/nature12782.html#
