Pilot study of the reducing effect on amyloidosis in vivo by three FDA pre-approved drugs via the Alzheimer's APP 5' untranslated region.
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), N-acetyl 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 Abeta-40 and Abeta-42 Abeta as pmol Abeta per gram of mouse brain cortex in drug treated and placebo animals. The relative levels of Abeta 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 anti-amyloid trend for paroxetine, NAC and erythromycin. The potential for conducting further studies with these compounds using larger cohorts of TgCRND8 mice is discussed.
Genetics and Aging Research Unit, Department of Psychiatry, Massachusetts General Hospital, Boston, MA 02125, USA. Jrogers@partners.org.
Stephanie
S
Tucker
Michelle
M
Ahl
Ashley
A
Bush
David
D
Westaway
Xudong
X
Huang
Jack T
JT
Rogers
D020121:5' Untranslated Regions / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000111:Acetylcysteine / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017277:Drug Approval; D015507:Drugs, Investigational / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D004917:Erythromycin / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D008822:Mice, Transgenic; D017374:Paroxetine / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D010865:Pilot Projects
D020121:5' Untranslated Regions; D016564:Amyloid beta-Protein Precursor; D015507:Drugs, Investigational; D017374:Paroxetine; D004917:Erythromycin; D000111:Acetylcysteine