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Disease models

Long-term, Plasmodium cynomolgi-infected primary hepatocyte culture to screen for malaria therapeutics

Long-term, P. cynomolgi-infected primary hepatocyte cultures could be used to identify therapeutics that prevent malaria relapse. Screening of compounds to eliminate quiescent Plasmodium hypnozoites currently relies on macaque models. Macaca fascicularis primary hepatocytes and a human hepatoma cell line were cocultured on a collagen layer and covered with a matrigel layer, resulting in long-term primary hepatocyte cultures that could support P. cynomolgi infection for about 40 days. In the
P. cynomolgi-infected cocultures, the generic antimalarial atovaquone eliminated the parasitic hypnozoite-derived schizont form but spared the quiescent hypnozoite form, which could be activated at an increased rate by histone methyltransferase inhibitors. Next steps include using the assay to evaluate the efficacy of different drug combinations to both activate and kill the parasite.

SciBX 7(10); doi:10.1038/scibx.2014.295
Published online March 13, 2014

Culturing system unpatented; licensing status not applicable; human hepatoma cell line used in study, HepaRG, patented by Institut National de la Santé et de la Recherche Médicale (INSERM); licensed by Biopredic International

Dembélé, L. et al. Nat. Med.; published online Feb. 9, 2014;
Contact: Georges Snounou, Pierre and Marie Curie University, Paris, France