Translational Inhibition of APP by Posiphen: Efficacy, Pharmacodynamics, and Pharmacokinetics in the APP/PS1 Mouse

Overview

Journal Alzheimers Dement (N Y)

Date 2018 Jun 30

PMID 29955650

Citations 22

Authors

Andrew F Teich

Ekta Sharma

Eliza Barnwell

Hong Zhang

Agnieszka Staniszewski

Tadanobu Utsuki

Vasudevaraju Padmaraju

Cheryl Mazell

Apostolia Tzekou

Kumar Sambamurti

Ottavio Arancio

Maria L Maccecchini

Affiliations

Soon will be listed here.

Abstract

Introduction: Translational inhibition of amyloid precursor protein (APP) by Posiphen has been shown to reduce APP and its fragments in cell culture, animal models, and mildly cognitively impaired patients, making it a promising drug candidate for the treatment of Alzheimer's disease.

Methods: We used a mouse model of Alzheimer's disease (APP/presenilin-1) to examine Posiphen's efficacy, pharmacodynamics, and pharmacokinetics.

Results: Posiphen treatment normalized impairments in spatial working memory, contextual fear learning, and synaptic function in APP/presenilin-1 mice, without affecting their visual acuity, motor skills, or motivation and without affecting wild-type mice. Posiphen had a prolonged effect in reducing APP and all related peptides for at least 9 hours after the last dose. Its concentration was higher in the brain than in plasma, and the most abundant metabolite was N-norPosiphen.

Discussion: This is the first study demonstrating the therapeutic efficacy of inhibiting the translation of APP and its fragments in an Alzheimer's disease model.

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