Drug-Related Brain Vacuolation as an Unusual Presentation of Neurotoxicity in Sprague Dawley Rats

Bhanu P. Singh, Megan R. Wilichinsky, Kathryn E. Bowenkamp, Mark T. Butt, Anne C. Carey, Sandra Chang, Anne E. Chester, Shelly N. Moores, Luke Muhumuza, Adrian S. Ray, Alok K. Sharma, Leigh Ann Burns-Naas, Gilead Sciences Inc, Foster City, Independent Toxicologic Pathology Consultant, Aligos Therapeutics, South San Francisco, Los Altos, Alnylam Pharmaceuticals, Mass General Brigham Ventures, Magnolia Toxicology Consulting LLC, Traverse City

International Journal of Toxicology

Published online on July 14, 2026

Abstract

International Journal of Toxicology, Ahead of Print.
In a 4-week rat study, a nucleotide prodrug antiviral agent containing a synthetic non-natural amino acid (C-331) induced a dose-related vacuolation in the brain’s white matter tracts without concurrent neuronal loss, gliosis, or neurological deficits. ...