Development of Bithionol against botulinum neurotoxins

SummaryShield Pharma and United States Department of Agriculture (USDA) scientists recentlydiscovered that bithionol, a compound with known antihelmintic properties, acts as a host-oriented inhibitor of botulinum neurotoxin serotype A (BoNT/A). Early studies showed thatbithionol inhibits BoNT/A-induced death in vivo. Based upon these promising studies, ShieldPharma is developing bithionol for the treatment of botulism. Currently, the only availablebotulism treatments are intravenous biological drugs. The development of an oral smallmolecule drug to treat botulism would address an unmet medical need, since the currentequine-produced therapy requires more expensive manufacturing, special storage andintravenous administration. The specific aims of this project are 1) to obtain literature that supports nonclinical andclinical safety and pharmacokinetics/toxicokinetics, 2) to evaluate the pharmacokinetics andtoxicity of bithionol in mice, and 3) to determine the therapeutic range and timing (interventive orprophylactic) of bithionol against the most deadly BoNT serotypes A, B, and E using an in vivoSwiss Webster mouse model of botulism intoxication.