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

Tucker, Stephanie; Ahl, Michelle; Bush, Ashley; Westaway, David; Xudong Huang; Rogers, Jack T.
April 2005
Current Alzheimer Research;Apr2005, Vol. 2 Issue 2, p249
Academic Journal
A pilot study was conducted employing a well known mouse model for Alzheimer's disease to evaluate the anti-amyloid efficacy of three FDA pre-approved drugs. Paroxetine (SSRI and APP 5'UTR 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 A�-40 and A�-42 A� as pmol A� 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 5'UTR 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.


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