Federal Grant Award Summary

The National Institute of Allergy and Infectious Diseases (NIAID) awarded University of Wisconsin–Madison a $791,200 Project Grant (CFDA 93.855: Allergy and Infectious Diseases Research) effective July 1, 2026, through June 30, 2031, to develop optimized pharmaceutical inhibitors targeting Naegleria fowleri, a parasitic amoeba responsible for primary amebic meningoencephalitis with a mortality rate exceeding 97 percent. The research team will design and synthesize novel heterocyclic compounds, conduct in vitro potency and cytotoxicity assays, evaluate pharmacokinetic (PK) properties in rodent models, and assess maximum tolerated dosing and efficacy with and without co-therapy using existing drug cocktails (amphotericin B, posaconazole, miltefosine). Deliverables include optimized preclinical lead compounds suitable for advancement toward clinical development, characterized by demonstrated rodent efficacy, acceptable safety profiles, and balanced absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties.

The research program incorporates parallel mechanistic studies to identify and validate biological targets through genetic analysis, RNA sequencing, and biochemical pull-down analyses. Three research teams led by Drs. Golden, Morris, and Meibom will collaborate on compound optimization, in vitro screening, pharmacokinetic assessment, and target validation. The ultimate objective addresses an unmet clinical need, as no FDA-approved therapies currently exist for N. fowleri infection; successful compounds emerging from this research would provide evidence-based treatment options to improve survival outcomes in patients diagnosed with this rapidly fatal parasitic infection.