BioCentury
ARTICLE | Distillery Therapeutics

Neurology

January 31, 2018 12:53 AM UTC

Mouse studies identified a prodrug of a TrkB agonist that could help treat AD. Chemical synthesis and testing in mouse-based PK assays of prodrugs of a 7,8-dihydroxyflavone-based TrkB agonist yielded a carbamate-functionalized analog that had a plasma half-life of 3.7 hours and whose active drug substance had a twofold higher bioavailability and greater area under the curve (AUC) for brain concentration-time than the free agonist. In a mouse model of AD, the prodrug increased synaptic density in the hippocampus and spatial memory and decreased levels of Aβ40 and phosphorylated tau in the brain and numbers of β amyloid plaques in the hippocampus and cortex compared with vehicle. Next steps by Shanghai Braegen Pharmaceuticals Co. Ltd. include clinical testing of the prodrug in AD...