Emory University has received a USD 1.87 million NIH U01 grant to advance an EP2 receptor antagonist toward IND-enabling studies for Alzheimer's disease, funded through the National Institute on Aging under award 5U01AG088113-03. The three-year award, running through mid-2029, supports Emory University researchers Thota Ganesh and Tage Honore in pushing a novel anti-neuroinflammatory candidate through toxicology and pharmacokinetic characterization required before first-in-human testing.
The program targets EP2, a prostaglandin-E2 receptor acting downstream of COX-2 that the investigators say drives a self-amplifying neuroinflammatory cycle in the Alzheimer's brain. Rather than blocking COX-2 broadly—an approach associated with cardiovascular toxicity during chronic dosing—the team's antagonists aim to selectively interrupt EP2 signaling. Preliminary data cited in the grant show the compounds reduced neuroinflammation and amyloid burden in 5xFAD mice and produced cognition-sparing effects in status epilepticus and sepsis models. The funded work will now define pharmacokinetic/pharmacodynamic relationships against AD pathology markers in blood, cerebrospinal fluid and brain tissue across two transgenic mouse models representing early- and late-onset disease, alongside NOAEL and therapeutic index studies required for an FDA investigational new drug filing.
The project sits apart from the amyloid- and tau-targeted antibodies that dominate the current AD pipeline, instead pursuing an oral small-molecule strategy aimed at neuroinflammation—a mechanism that has drawn NIH interest as amyloid-focused therapies have shown only modest effects on disease progression. No EP2-targeted compound has reached human testing for Alzheimer's disease to date.