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Quick, high-volume test offers fast track in search for Alzheimer's drugs
Date:11/15/2012

nt depending on the dosage could still climb after the same time period.

Damian Crowther, a group leader in the Department of Genetics at Cambridge who created and supplied the flies used in the Princeton research but had no active role in the work, said that D737 demonstrated a notable ability to suppress in fruit flies the same neurological, physical and mental deficits seen in humans with Alzheimer's.

"It's not common to see such a strong effect in the fly model. Of the compounds that my lab tests, which have been through rigorous in vitro screening, we see effects as good as this in only 5 to 10 percent," Crowther said. "To find that a compound administered orally is able to show beneficial effects on both of these fly phenotypes indicates that the drug can access the neurons and, once within the brain, presumably control the aggregation of amyloid beta peptides."

Crowther said the Princeton research further supports the approach of curbing the buildup of Aβ42 and related variants of the amyloid beta peptide to treat Alzheimer's. In the middle stages of accumulation, variations of the peptide can be highly toxic to neurons and kill them, he said. But the work by Hecht and his co-authors helps show that blocking amyloid-beta aggregation can be safe and potent.

"There is always a worry when looking for aggregation-blocking agents that the aggregation process may be interrupted at the wrong point," Crowther said.

"Further work should try to characterize in an in vivo system exactly where this compound halts or modifies the aggregation process," he said. "For a beneficial effect we don't need to completely block aggregation indeed, amyloid formation is a thermodynamically inevitable process. It could be that the compound simply modulates the aggregation process so that the most toxic intermediates are less populated."

Although the compound's success in flies would not necessarily translate to humans, Fort
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Contact: Morgan Kelly
mgnkelly@princeton.edu
609-258-5729
Princeton University
Source:Eurekalert  

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