Thursday, March 13, 2014
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cynomolgi-infected primary hepatocyte culture to screen for malaria
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
Published online March 13, 2014
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,
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