Abstract
INTRODUCTION
Small molecules and antibodies are being developed to lower amyloid beta (Aβ) peptides.
METHODS
We describe MEDI1814, a fully human high-affinity monoclonal antibody selective for Aβ42, the pathogenic self-aggregating species of Aβ.
RESULTS
MEDI1814 reduces free Aβ42 without impacting Aβ40 in the cerebrospinal fluid of rats and cynomolgus monkeys after systemic administration. MEDI1814 administration to patients with Alzheimer’s disease (AD; n = 57) in single or repeat doses up to 1800 mg intravenously or 200 mg subcutaneously was associated with a favorable safety and tolerability profile. No cases of amyloid-related imaging abnormalities were observed. Predictable dose-proportional changes in serum exposures for MEDI1814 were observed across cohorts. Cerebrospinal fluid (CSF) analysis demonstrated central nervous system penetration of MEDI1814. Pharmacodynamic data showed dose-dependent suppression of free Aβ42, increases in total (bound and free) Aβ42, but no change in total Aβ40 in CSF across doses.
DISCUSSION
MEDI1814 offers a differentiated approach to impacting Aβ in AD via selective reduction of free Aβ42.
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This post is Copyright: Christopher Lloyd,
Per‐Ola Freskgård,
Philip Newton,
David Lowne,
Adrian Nickson,
Anna Bogstedt,
Susanna Eketjäll,
Kina Höglund,
Susanne Gustavsson,
Fraser Welsh,
Tharani Chessell,
Mary McFarlane,
Ratan V. Bhat,
Richard Turner,
Michael S. Perkinton,
Zulma Santisteban Valencia,
Eva Lindqvist,
Michael Pomfret,
Amanda D. Dudley,
Tristan J. Vaughan,
Maria T. Groves,
Fanni Natanegara,
Yingdong Feng,
John R. Sims,
Nicholas Kyle Proctor,
Jeffrey L. Dage,
Craig Shering,
Keith Tan,
Thor Ostenfeld,
Andy Billinton,
Iain P. Chessell | September 25, 2024