Pilot Study of the Reducing Effect on Amyloidosis In Vivo by Three FDA Pre-Approved Drugs Via the Alzheimers APP 5Untranslated Region

Stephanie      Tucker; Michelle      Ahl; Ashley      Bush; David      Westaway; Xudong      Huang; Jack   T.   Rogers

doi:10.2174/1567205053585855

Abstract

A pilot study was conducted employing a well known mouse model for Alzheimers disease to evaluate the anti-amyloid efficacy of three FDA pre-approved drugs. Paroxetine (SSRI and APP 5UTR directed lead compound), Nacetyl cysteine (antioxidant), and erythromycin (macrolide antibiotic) were provided to the drinking water of TgCRND8 mice for three months. This report provides data that measured the steady-state levels of amyloid Aβ-40 and Aβ-42 Aβ as pmol Aβ per gram of mouse brain cortex in drug treated and placebo animals. The relative levels of Ab peptide levels were reduced after exposure of mice to paroxetine (N=5), NAC (N=7), and erythromycin (N=7) relative to matched placebo counterparts. These results demonstrated proof-of concept for a strategy to further screen the APP 5UTR target to identify novel drugs that exhibit anti-amyloid efficacy in vivo. These data also demonstrated a statistically significant antiamyloid trend for paroxetine, NAC and erythromycin. The potential for conducting further studies with these compounds using larger cohorts of TgCRND8 mice is discussed.

Keywords: amyloid precursor protein(app), desferrioxamine, phenserine, dimercaptopropanol, antioxidant, transgenic mice, (nsaid), nucleotide