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[P4–039]: PAN‐TAU ANTIBODY BIIB076 EXHIBITS PROMISING SAFETY AND BIOMARKER PROFILE IN CYNOMOLGUS MONKEY TOXICITY STUDY
Author(s) -
Czerkowicz Julie,
Chen Weiping,
Wang Qin,
Shen Chase,
Wager Carrie,
Stone Ivan,
Stebbins Chris,
Lamb Martin,
Setser John,
Cantone Gina,
Graham Danielle
Publication year - 2017
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.2017.06.1903
Subject(s) - toxicity , adverse effect , pharmacology , antibody , biomarker , medicine , histopathology , monoclonal antibody , drug , immunology , chemistry , pathology , biochemistry
phosphorylated tau. In experiment 2, PS19 mice were fed chow containing 0.4% UDCA or vehicle beginning at age 3 months and continuing until behavioral testing and sacrifice at age 9 months. Results: Experiment 1: UDCA was well tolerated, with no significant effects on body weight or survival. UDCA treatment was associated with improved Morris Water Maze performance in male h-tau mice (on Probe Test at 72 hours after training, wt mice spent 37% of time in target quadrant, vehicle treated h-tau mice 25%, UDCA treated htau mice 34%). Plasma UDCA 1⁄4 7206794 ng/ml in UDCA treated mice (n1⁄412) and 33648 (p1⁄40.006) in vehicle treated mice (n1⁄412). Brain UDCA 1⁄4 41650 pg/mg tissue in UDCA treated mice vs 661 (p1⁄40.02) for vehicle. Plasma TUDCA 1⁄4 3846130 ng/ml in UDCA treated mice vs 20637 (p<0.00001) in vehicle, and brain TUDCA1⁄4 766 pg/mg tissue in UDCA treated mice vs 0 in vehicle treated mice (p1⁄40.0002). The ratio of hippocampal phosphorylated tau: total tau was reduced in UDCA treated htau mice compared to vehicle-treated mice on Western blot. Experiment 2: Long-term UDCA has been well tolerated in PS19 mice. Analysis of behavior and brain tissue is ongoing. Conclusions: UDCA is well tolerated with chronic treatment, bioavailable, CNS-penetrant, and demonstrated neuroprotectant properties in preliminary studies in mouse models of tau-opathy.