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P2‐302: GSI‐953 is a potent APP‐selective gamma‐secretase inhibitor for the treatment of Alzheimer's disease
Author(s) -
Jacobsen Steven,
Comery Thomas,
Aschmies Suzan,
Zhou Hua,
Jin Mei,
Atchison Kevin,
Xu Jane,
Wagner Erik,
Sonnenberg-Reines June,
Kreft Anthony,
Sun Roy,
Liu Peimin,
Gong Xiaohai,
Zaleska Margaret,
Adkins Karissa,
Oganesian Aram,
Folletti Maximillian,
Wan Hong,
Mayer Scott,
Hoke Molly,
Reinhart Peter,
Harrison Boyd,
Magolda Ron,
Pangalos Menelas,
Martone Robert
Publication year - 2008
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2008.05.1379
Subject(s) - gamma secretase , amyloid precursor protein secretase , amyloid precursor protein , notch signaling pathway , chemistry , presenilin , in vitro , pharmacology , genetically modified mouse , alzheimer's disease , transgene , microbiology and biotechnology , biochemistry , receptor , biology , medicine , disease , gene
meters, p 0.007). Transgenic animals of the CHF5074-treated group performed significantly better than transgenic controls on the distance moved (2.12 0.33 meters, p 0.025). Ibuprofen-treated animals did not perform significantly better than transgenic controls. Long-term treatment with CHF5074 was well tolerated as mortality and body weight gain did not differ from transgenic controls. Conclusions: Chronic CHF5074 treatment significantly reduced brain -amyloid burden and associated microglia inflammation and attenuated spatial memory deficit in hAPP mice. This novel gamma-secretase modulator has the potential to be an effective and safe therapeutic agent for AD.