Federal Project Grant Award Summary

Wake Forest University Health Sciences received a $480,448 Project Grant from the National Institute of Allergy and Infectious Diseases (NIAID) under the Allergy and Infectious Diseases Research program (CFDA 93.855), awarded June 1, 2026, with a completion date of May 31, 2028. The grant supports the development of improved aminopyridine analogs as symptomatic treatments for botulism, building on prior Department of Defense-funded work demonstrating that 3,4-diaminopyridine (3,4-DAP), a voltage-gated potassium channel blocker, reverses botulism symptoms by increasing acetylcholine release at compromised neuromuscular junctions.

The project addresses critical limitations of current 3,4-DAP treatment to advance its development as a medical countermeasure for botulinum neurotoxin (BONT) exposure. Research activities will focus on designing and synthesizing next-generation aminopyridine analogs that reduce seizure liability from central nervous system penetration while improving pharmacokinetic consistency by minimizing variability caused by N-acetyltransferase-2 polymorphisms. These enhanced compounds are intended to support regulatory approval pathways and expand clinical utility for treating BONT-exposed patients who currently face prolonged mechanical ventilation and limited treatment options beyond post-exposure antitoxin administration, which cannot reverse toxin-induced paralysis once internalized into motor neurons.