Epitopes described in "Effect of immunotherapy with bapineuzumab on cerebrospinal fluid biomarker levels in patients with mild to moderate Alzheimer disease."

Article Authors:Kaj Blennow; Henrik Zetterberg; Juha O Rinne; Stephen Salloway; Jenny Wei; Ronald Black; Michael Grundman; Enchi Liu; AAB-001 201/202 Investigators
Article Title:Effect of immunotherapy with bapineuzumab on cerebrospinal fluid biomarker levels in patients with mild to moderate Alzheimer disease.
Reference Detail
Reference ID:1025227
Abstract:BACKGROUND: Given the slow and variable clinical course of Alzheimer disease, very large and extended clinical trials are needed to identify a beneficial clinical effect of disease-modifying treatments. Therefore, biomarkers are essential to prove that an anti--amyloid (A) drug candidate affects both A metabolism and plaque load as well as downstream pathogenic mechanisms. OBJECTIVE: To evaluate the effect of the anti-A monoclonal antibody bapineuzumab on cerebrospinal fluid (CSF) biomarkers reflecting A homeostasis, neuronal degeneration, and tau-related pathology in patients with Alzheimer disease. DESIGN: Two phase 2, multicenter, randomized, double-blind, placebo-controlled clinical trials of 12-month duration. SETTING: Academic centers in the United States (Study 201) and England and Finland (Study 202). PATIENTS: Forty-six patients with mild to moderate Alzheimer disease. INTERVENTIONS: Patients received either placebo (n = 19) or bapineuzumab (n = 27) in 3 or 4 ascending dose groups. MAIN OUTCOME MEASURES: Changes between end of study and baseline in the exploratory CSF biomarkers A1-42, AX-42, AX-40; total tau (T-tau); and phosphorylated tau (P-tau). RESULTS: Within the bapineuzumab group, a decrease at end of study compared with baseline was found both for CSF T-tau (-72.3 pg/mL) and P-tau (-9.9 pg/mL). When comparing the treatment and placebo groups, this difference was statistically significant for P-tau (P = .03), while a similar trend for a decrease was found for T-tau (P = .09). No clear-cut differences were observed for CSF A. CONCLUSIONS: To our knowledge, this study is the first to show that passive A immunotherapy with bapineuzumab results in decreases in CSF T-tau and P-tau, which may indicate downstream effects on the degenerative process. Cerebrospinal fluid biomarkers may be useful to monitor the effects of novel disease-modifying anti-A drugs in clinical trials. TRIAL REGISTRATIONS clinicaltrials.gov Identifier: NCT00112073, EudraCT Identifier: 2004-004120-12, and isrctn.org Identifier: ISRCTN17517446.
Affiliations:Clinical Neurochemistry Laboratory, Sahlgrenska Academy, University of Gothenburg, Mölndal, Sweden. kaj.blennow@neuro.gu.se
Reference Type:Literature
PubMed ID:22473769
Journal:Arch Neurol
Journal Volume:69
Article Pages:1002-10
Journal ISSN:1538-3687
Article Chemical List:Amyloid beta-Peptides;Antibodies, Monoclonal, Humanized;Biological Markers;Peptide Fragments;amyloid beta-protein (1-42);bapineuzumab;tau Proteins
Article MeSH List:Aged; Alzheimer Disease(cerebrospinal fluid; drug therapy; epidemiology); Amyloid beta-Peptides(cerebrospinal fluid); Antibodies, Monoclonal, Humanized(therapeutic use); Biological Markers(cerebrospinal fluid); Cohort Studies; Double-Blind Method; England(epidemiology); Female; Finland(epidemiology); Humans; Immunotherapy(methods); Male; Middle Aged; Peptide Fragments(cerebrospinal fluid); Treatment Outcome; United States(epidemiology); tau Proteins(cerebrospinal fluid)
Curation Last Updated:2014-10-03 22:48:54