Epitopes described in "Safety and biomarker effects of solanezumab in patients with Alzheimer's disease."

Reference
Article Authors:Martin Farlow; Steven E Arnold; Christopher H van Dyck; Paul S Aisen; B Joy Snider; Anton P Porsteinsson; Stuart Friedrich; Robert A Dean; Celedon Gonzales; Gopalan Sethuraman; Ronald B DeMattos; Richard Mohs; Steven M Paul; Eric R Siemers
Article Title:Safety and biomarker effects of solanezumab in patients with Alzheimer's disease.
Reference Detail
Reference ID:1025270
Abstract:OBJECTIVES: To assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of 12 weekly infusions of solanezumab, an anti--amyloid (A) antibody, in patients with mild-to-moderate Alzheimer's disease. Cognitive measures were also obtained. METHODS: In this phase 2, randomized, double-blind, placebo-controlled clinical trial, 52 patients with Alzheimer's disease received placebo or antibody (100 mg every 4 weeks, 100 mg weekly, 400 mg every 4 weeks, or 400 mg weekly) for 12 weeks. Safety and biomarker evaluations continued until 1 year after randomization. Both magnetic resonance imaging and cerebrospinal fluid (CSF) examinations were conducted at baseline and after the active treatment period. The A concentrations were measured in plasma and CSF, and the Alzheimer's Disease Assessment Scale-cognitive portion was administered. RESULTS: Clinical laboratory values, CSF cell counts, and magnetic resonance imaging scans were unchanged by treatment, and no adverse events could be clearly related to antibody administration. Total (bound to antibody and unbound) A(1-40) and A(1-42) in plasma increased in a dose-dependent manner. Antibody treatment similarly increased total A(1-40) and A(1-42) in CSF. For patients taking 400 mg weekly, antibody treatment decreased unbound A(1-40) in CSF (P < .01), but increased unbound A(1-42) in CSF in a dose-dependent manner. The Alzheimer's Disease Assessment Scale-cognitive portion was unchanged after the 12-week antibody administration. CONCLUSIONS: Antibody administration was well tolerated with doses up to 400 mg weekly. The dose-dependent increase in unbound CSF A(1-42) suggests that this antibody may shift A equilibria sufficiently to mobilize A(1-42) from amyloid plaques.
Affiliations:Department of Neurology, Indiana University School of Medicine, Indianapolis, USA.
Date:2012
Reference Type:Literature
PubMed ID:22672770
Journal:Alzheimers Dement
Journal Volume:8
Article Pages:261-71
Journal ISSN:1552-5279
Article Chemical List:6-iodo-2-(4'-dimethylamino-)phenyl-imidazo(1,2-a)pyridine;Amyloid beta-Peptides;Antibodies, Monoclonal, Humanized;Peptide Fragments;Pyridines;amyloid beta-protein (1-40);amyloid beta-protein (1-42);solanezumab
Article MeSH List:Aged; Aged, 80 and over; Alzheimer Disease(cerebrospinal fluid; complications; drug therapy; radionuclide imaging); Amyloid beta-Peptides(cerebrospinal fluid); Antibodies, Monoclonal, Humanized(therapeutic use); Cognition Disorders(drug therapy; etiology); Dose-Response Relationship, Drug; Double-Blind Method; Electroencephalography; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neuropsychological Tests; Peptide Fragments(cerebrospinal fluid); Psychiatric Status Rating Scales; Pyridines(diagnostic use); Tomography, Emission-Computed, Single-Photon; Treatment Outcome
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