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O3–07–02: G‐protein signalling associated with membrane APP‐CTF accumulation
Author(s) -
Parent Angele,
Deyts Carole
Publication year - 2013
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.2013.04.274
Subject(s) - neurite , amyloid precursor protein , alpha secretase , ectodomain , microbiology and biotechnology , intracellular , p3 peptide , senile plaques , chemistry , amyloid beta , nicastrin , amyloid precursor protein secretase , adam10 , biology , alzheimer's disease , receptor , biochemistry , medicine , peptide , in vitro , disintegrin , disease , metalloproteinase , matrix metalloproteinase
statistically significantly, favored T-817MA on the ADCS-CGIC (52.4% vs. 38.3% worsened; P 1⁄4.077) and ADCS-ADL (1.9, 95%CI: -1.1, 4.9; P1⁄4.215); NPI differences favored placebo (2.8, 95%CI: 0.0, 5.6, P 1⁄4.048); mITT outcomes were similar. AEs occurred in 66.1% and 73.7% of placebo and T-817MA participants, respectively; 6.6% and 10.5%, respectively, discontinued because of AEs. Most frequent AEs, 5% for T-817MA, included diarrhea (7.1% vs. 18.9%), nausea (0.5% vs. 5.3%), dizziness (3.3% vs. 5.3%) and headache (4.4% vs. 5.3%). SAEs were reported for 22 (12.0%) and 31 (16.3%) with 1 and 2 judged possibly related. Total brain and bilateral hippocampal volumes changes for the 10 placebo and 7 T-817MA participants were -0.7% vs. -0.4% and -5.3% vs. -4.1%, respectively, and non-significant between treatments. Conclusions: T-817MA appeared safe, tolerable, and showed potential for attenuating cognitive, functional and global decline, compatiblewith an approximate 50% reduction inclinical progression over 52weeks.Unexpectedly, highdropout rates inboth placebo and drug groups limit inferences. Confirmatory trials are needed.