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P1‐054: MOBILE COGNITIVE INTERVENTION IN OLDER VETERANS WITH TRAUMATIC BRAIN INJURY: RESULTS FROM THE BRAVE (BRAIN AGING IN VETERANS) TRAINING PILOT STUDY
Author(s) -
Kaup Allison R.,
Schachtner Jessica,
Byers Amy L.,
Barnes Deborah E.,
Anguera Joaquin A.,
Harmell Alexandrea L.,
Amaya Maria-Paulina,
Gross Margaret,
Yaffe Kristine
Publication year - 2019
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.2019.06.079
Subject(s) - traumatic brain injury , executive functions , neuropsychology , cognition , intervention (counseling) , randomized controlled trial , cognitive training , medicine , human multitasking , executive dysfunction , working memory , physical medicine and rehabilitation , physical therapy , psychology , psychiatry , cognitive psychology
affinity for phosphorylated tau (p217+). This antibody depletes toxic tau species in in vitro seeding assays and reduces tau seeding in in vivomodels. A sensitive assay has been developed to measure p217+tau fragments in the cerebrospinal fluid (CSF), and changes in CSF levels of p217+ tau may serve as a surrogate for changes in the levels of extracellular tau seed in the ISF following antibody administration. Methods: A randomized, double blind, placebo controlled single ascending dose (SAD) study has been conducted in healthy subjects aged 55-75 years. Five cohorts of 8 subjects each were administered placebo or a single dose of JNJ-63733657 intravenously in a dose ranging study. Subjects were followed for 92 days, and serum and CSF samples were collected. Safety, tolerability, pharmacokinetics (PK; serum and CSF), and the effect of JNJ-63733657 on CSF levels of p217+tau fragments (pharmacodynamic (PD) response) were evaluated. Results: Following single dose administration, JNJ-63733657 was generally safe and welltolerated and demonstrated linear PK in serum. Dose-dependent increases in exposures were observed. CSF exposures were w0.2% of serum levels. There were dose dependent reductions in p217+ tau in CSF of healthy subjects following antibody administration. Conclusions: JNJ-63733657 exhibits clearance of toxic tau species in preclinical models and to date shows a favorable clinical profile and biomarker response following single dose administration.