Federal Grant Award Summary

The National Institute of Allergy and Infectious Diseases (NIAID) awarded Scripps Research Institute a $518,450 Project Grant under the Allergy and Infectious Diseases Research program (CFDA 93.855) effective June 10, 2026, with completion targeted for May 31, 2028. This research initiative focuses on developing a Proteolysis Targeting Chimera (PROTAC) strategy to combat botulinum neurotoxicity, specifically targeting botulinum neurotoxin serotype A (BONT/A). The project aims to integrate previously identified small-molecule inhibitors of the zinc metalloprotease light chain with targeted protein degradation technology to achieve sustained toxin elimination in intoxicated neurons, addressing a significant gap in current therapeutic options where existing antitoxin treatments can only slow disease progression rather than rescue affected cells.

The deliverables from this research will include structural optimization of BONT/A light chain inhibitors, development of bifunctional therapeutic compounds incorporating targeted protein degradation capabilities, and preclinical validation through cellular and animal model testing. This research represents a direct response to the CDC classification of botulinum neurotoxins as Category A bioterrorism threats and addresses the critical clinical need for an approved therapeutic to treat botulism, which currently lacks effective post-intoxication rescue treatments despite the extreme lethality and weaponization potential of these toxins.