Therapeutic Efficacy of Bumped Kinase Inhibitor 1369 in a Pig Model of Acute Diarrhea Caused by Cryptosporidium hominis
June 26, 2018
Sangun Lee, Melanie Ginese, Gillian Beamer, Hillary R. Danz, Donald J. Girouard, Susan P. Chapman-Bonofiglio, Minhee Lee, Matthew A. Hulverson, Ryan Choi, Grant R. Whitman, Kayode K. Ojo, Samuel L. M. Arnold, Wesley C. Van Voorhis, Saul Tzipori
Antimicrobial Agents and Chemotherapy: 2018 Jun 26;62(7). pii: e00147-18. doi: 10.1128/AAC.00147-18. | PMID: 29661877
Abstract
Recent reports highlighting the global significance of cryptosporidiosis among children have renewed efforts to develop control measures. We evaluated the efficacy of bumped kinase inhibitor (BKI) 1369 in the gnotobiotic piglet model of acute diarrhea caused by Cryptosporidium hominis, the species responsible for most human cases. Five-day treatment with BKI 1369 reduced signs of disease early during treatment compared to those of untreated animals. Piglets treated with BKI 1369 exhibited significant reductions of oocyst excretion, mucosal colonization by C. hominis, and mucosal lesions, which resulted in considerable symptomatic improvement. BKI 1369 reduced the parasite burden and disease severity in the gnotobiotic pig model. Together these data suggest that a BKI-mediated therapeutic may be an effective treatment against cryptosporidiosis.