RT Journal Article
T1 An Early Treatment With BKI-1748 Exhibits Full Protection Against Abortion and Congenital Infection in Sheep Experimentally Infected With Toxoplasma gondii
A1 Sánchez Sánchez, Roberto
A1 Imhof, Dennis
A1 Hecker, Yanina Paola
A1 Ferré Pérez, Ignacio
A1 Re, Michela Tatiana
A1 Moreno Gonzalo, Javier
A1 Blanco Murcia, Francisco Javier
A1 Mejías López, Elena
A1 Hulverson, Matthew A.
A1 Choi, Ryan
A1 Arnold, Samuel L. M.
A1 Ojo, Kayode K.
A1 Barrett, Lynn K.
A1 Hemphill, Andrew
A1 Van Voorhis, Wesley C.
A1 Ortega Mora, Luis Miguel
AB Congenital toxoplasmosis in humans and in other mammalian species, such as small ruminants, is a well-known cause of abortion and fetal malformations. The calcium-dependent protein kinase 1 (CDPK1) inhibitor BKI-1748 has shown a promising safety profile for its use in humans and a good efficacy against Toxoplasma gondii infection in vitro and in mouse models. Ten doses of BKI-1748 given every other day orally in sheep at 15 mg/kg did not show systemic or pregnancy-related toxicity. In sheep experimentally infected at 90 days of pregnancy with 1000 TgShSp1 oocysts, the BKI-1748 treatment administered from 48 hours after infection led to complete protection against abortion and congenital infection. In addition, compared to infected/untreated sheep, treated sheep showed a drastically lower rectal temperature increase and none showed IgG seroconversion throughout the study. In conclusion, BKI-1748 treatment in pregnant sheep starting at 48 hours after infection was fully effective against congenital toxoplasmosis.
PB Oxford University Press
SN 0022-1899
YR 2023
FD 2023-10-27
LK https://hdl.handle.net/20.500.14352/104468
UL https://hdl.handle.net/20.500.14352/104468
LA eng
NO Roberto Sánchez-Sánchez, Dennis Imhof, Yanina P Hecker, Ignacio Ferre, Michela Re, Javier Moreno-Gonzalo, Javier Blanco-Murcia, Elena Mejías-López, Matthew A Hulverson, Ryan Choi, Samuel L M Arnold, Kayode K Ojo, Lynn K Barrett, Andrew Hemphill, Wesley C Van Voorhis, Luis Miguel Ortega-Mora, An Early Treatment With BKI-1748 Exhibits Full Protection Against Abortion and Congenital Infection in Sheep Experimentally Infected With Toxoplasma gondii, The Journal of Infectious Diseases, Volume 229, Issue 2, 15 February 2024, Pages 558–566, https://doi.org/10.1093/infdis/jiad470
NO Comunidad de Madrid
NO Department of Agriculture (US)
NO National Institutes of Health (US)
NO Swiss National Science Foundation
DS Docta Complutense
RD 5 abr 2025