Effective Treatment using Bumped Kinase Inhibitor 1708 in a Calf Clinical Model of Cryptosporidiosis

Cryptosporidium parvum, an apicomplexan parasite and the causative agent of cryptosporidiosis, contributes to a high burden in mortality and morbidity for humans and livestock. Currently, there are no reliably successful parasite-specific treatments for the debilitating diarrhea associated with the infection. Bumped kinase inhibitors (BKIs), which selectively target parasite calcium-dependent protein kinases (CDPKs), have been shown to decrease infections caused by several medical and veterinary-relevant parasites, including Toxoplasma gondii, Plasmodium falciparum, and Cryptosporidium parvum. In the present study, various dosing regimens of BKI-1708 were evaluated for safety and clinical efficacy in the calf model for cryptosporidiosis, specifically with the aim of finding a minimum effective dose. The majority of the different BKI dosages produced notable improvements across nearly all clinical and parasitological measures, including diarrhea severity, oocyst shedding, and overall health status. These results provide strong evidence for advancing BKI-1708 as a preclinical candidate for treatment of cryptosporidiosis.