Person:
Blanco Murcia, Francisco Javier

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First Name
Francisco Javier
Last Name
Blanco Murcia
URI
https://hdl.handle.net/20.500.14352/80497
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Veterinaria
Department
Medicina y Cirugía Animal
Area
Medicina y Cirugía Animal
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    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, 2023) Sánchez Sánchez, Roberto; Imhof, Dennis; Hecker, Yanina Paola; Ferré Pérez, Ignacio; Re, Michela Tatiana; Moreno Gonzalo, Javier; Blanco Murcia, Francisco Javier; Mejías López, Elena; Hulverson, Matthew A.; Choi, Ryan; Arnold, Samuel L. M.; Ojo, Kayode K.; Barrett, Lynn K.; Hemphill, Andrew; Van Voorhis, Wesley C.; Ortega Mora, Luis Miguel
    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.