Compounds that hit the target may be capable of curing, preventing and blocking the transmission of malaria
The discovery of Plasmodium falciparum phosphatidylinositol-4 kinase (PfPI4K) as the target of a novel experimental antimalarial compound class (the imidazopyrazines) is published online in the journal Nature1. PfPI4K is the first chemically validated target active in multiple malaria-causing species at multiple stages, raising hope for a treatment able to cure, prevent and block the transmission of malaria.
A research consortium comprising Novartis, Swiss Tropical and Public Health Institute, the Biomedical Primate Research Centre, The Netherlands and MMV initially identified the imidazopyrazines with funding from MMV and Wellcome Trust. An international team of scientists were able to identify PfPI4K as a target for the imidazopyrazine series by creating resistant parasite strains in the laboratory and using genetic sequencing to identify which genes had mutated to confer resistance. In all cases, the mutation occurred in the gene for PI4K, an enzyme involved in fatty acid metabolism across all stages in the parasite lifecycle.
"This new target for malaria provides an avenue to develop the next-generation antimalarial drugs that are capable of preventing, treating and blocking the spread of malaria, a key goal of Novartis," commented Thierry Diagana, Head of the Novartis Institute for Tropical Diseases.
Dr Richard Seabrook, Head of Business Development at the Wellcome Trust, said: “With growing resistance to existing therapies, we urgently need new malaria medicines to combat the spread of this deadly disease. This discovery is particularly exciting as it identifies a druggable target that is effective in multiple species of the malaria parasite and at all stages of the parasite lifecycle, features that are considered vital for a treatment capable of eliminating malaria.”
“Identifying the target for the imidazopyrazine chemical series is a huge scientific leap forward,” said Dr Timothy Wells, Chief Scientific Officer at MMV. “It’s exciting to see a new molecular target emerge with applications towards targeting the liver stages of the parasite. There is a real gap in the portfolio of new molecules in this area, and new medicines are urgently needed over the next decade to fully support malaria eradication efforts.”
Read the news story on the Novartis website.
1. McNamara CW et al. Targeting Plasmodium PI(4)K to eliminate malaria. Nature. 2013. doi: 10.1038/503186a.