This is a review of the development of bumped-kinase inhibitors (BKIs) for the therapy of One Health parasitic apicomplexan diseases. Many apicomplexan infections are shared between humans and livestock, such as cryptosporidiosis and toxoplasmosis, as well as livestock only diseases such as neosporosis. We have demonstrated proof-of-concept for BKI therapy in livestock models of cryptosporidiosis (newborn calves infected with Cryptosporidium parvum), toxoplasmosis (pregnant sheep infected with Toxoplasma gondii), and neosporosis (pregnant sheep infected with Neospora caninum). We discuss the potential uses of BKIs for the treatment of diseases caused by apicomplexan parasites in animals and humans, and the improvements that need to be made to further develop BKIs.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8582285PMC
http://dx.doi.org/10.1016/j.vetpar.2020.109336DOI Listing

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Article Synopsis
  • Drug development for congenital toxoplasmosis is challenging due to high adverse effects and poor efficacy of first-line therapies; bumped kinase inhibitors (BKIs) like BKI-1748 may offer a new treatment option.
  • In a study involving 19 pregnant sheep, those treated with BKI-1748 after infection showed lower fever and immunological responses compared to untreated counterparts.
  • The treated group had a higher percentage of healthy lambs at delivery and showed no evidence of congenital transmission of the parasite, unlike the untreated group where parasite DNA was detectable.
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