Kinase Inhibitors Target Proliferative Mechanism of Malaria Parasite

A group of researchers from the Ecole Polytechnique Federale de Lausanne’s (EPFL) Global Health Institute (GHI) and Inserm (Institut National de la Santé et de la Recherche Médicale, the French government agency for biomedical research) has discovered that a class of chemotherapy drugs originally designed to inhibit key signaling pathways in cancer cells also kills the parasite that causes malaria. The discovery could quickly open up a whole new strategy for combating this deadly disease. The research, published online on March 4, 2011, in the journal Cellular Microbiology, shows that the malaria parasite depends upon a signaling pathway present in the host – initially in liver cells, and then in red blood cells – in order to proliferate. The enzymes active in the signaling pathway are not encoded by the parasite, but rather hijacked by the parasite to serve its own purposes. These same pathways are targeted by a new class of molecules developed for cancer chemotherapy known as kinase inhibitors. When the GHI/Inserm team treated red blood cells infected with malaria with the chemotherapy drug, the parasite was stopped in its tracks. Professor Christian Doerig and his colleagues tested red blood cells infected with Plasmodium falciparum parasites and showed that the specific PAK-MEK signaling pathway was more highly activated in infected cells than in uninfected cells. When they disabled the pathway pharmacologically, the parasite was unable to proliferate and died. Applied in vitro, the chemotherapy drug also killed a rodent version of malaria (P. berghei), in both liver cells and red blood cells.
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