Bibliographic
The goal of the study is to test DP-155, a phospholipid derivative of NSAID indomethacin, safety and effects on brain Aβ levels in Tg2576 mice. Past studies have shown indomethacin inhibits Aβ formation via gamma-secretase inhibition through a COX-independent process in addition to its COX dependent anti-inflammatory and neuroprotective effects. However, long-term indomethacin use is limited by significant gastrointestinal and renal toxicities. In this study, DP-155, which is a lipid-modified indomethacin comprised of indomethacin linked to lecithin, had reduced toxicity as compared to indomethacin, and was equally efficacious in reducing brain Aβ. DP-155 had 3.5 times higher brain to serum ratio, which explains why DP-155 is efficacious in reducing brain Aβ with significantly lower toxicity in the gut and kidney, making this compound a potential therapeutic for Alzheimer's disease.