Shield Pharma and United States Department of Agriculture (USDA) scientists recently discovered that bithionol, a compound with known antihelmintic properties, acts as a host- oriented inhibitor of botulinum neurotoxin serotype A (BoNT/A). Early studies showed that bithionol inhibits BoNT/A-induced death in vivo. Based upon these promising studies, Shield Pharma is developing bithionol for the treatment of botulism. Currently, the only available botulism treatments are intravenous biological drugs. The development of an oral small molecule drug to treat botulism would address an unmet medical need, since the current equine-produced therapy requires more expensive manufacturing, special storage and intravenous administration.
The specific aims of this project are 1) to obtain literature that supports nonclinical and clinical safety and pharmacokinetics/toxicokinetics, 2) to evaluate the pharmacokinetics and toxicity of bithionol in mice, and 3) to determine the therapeutic range and timing (interventive or prophylactic) of bithionol against the most deadly BoNT serotypes A, B, and E using an in vivo Swiss Webster mouse model of botulism intoxication.
We discovered that a previously approved small molecule, acts as a host-oriented inhibitor of botulinum neurotoxin serotype A (BoNT/A). This project will expand our work by testing this compound in vivo against the three most common serotypes (A,B,E), across a range of pre- and post-exposure timing. Overall, these efforts are intended to support a subsequent Phase II application to support a nonclinical program, en route to commercializing an oral therapy against botulinum neurotoxin that is more easily manufactured, stored, and administered than existing treatments.
