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New Data Shows Combination Therapy is More Effective than Monotherapy in Removing Beta-Amyloid Plaques from the Brains of Mice
Date:7/13/2014

s the removal of the beta-amyloid protein. Compounds that are thought to work through these mechanisms have been studied in clinical trials on their own; however, most of the trials have not shown significant treatment effects. Therefore, many believe that multiple steps of the beta-amyloid deposition process need to be simultaneously targeted in order to remove significant quantities of the beta-amyloid pathology.

The non-clinical study results showed that when used on their own (as monotherapies), the beta-secretase inhibitor and the N3pG beta-amyloid antibody removed approximately 50 percent of the clumps of amyloid-beta protein, whereas the combination therapy resulted in an even more substantial 86 percent removal. Additionally, combination therapy significantly lowered deposited Aβ1-42 75 percent relative to the time zero controls. Histological analyses indicated that the BACE inhibitor monotherapy resulted in removal of diffuse deposits of beta-amyloid, the antibody monotherapy resulted in removal of cored plaques, and the combination therapy removed both the diffuse deposits and cored plaques. Multiple different types of biochemical analyses confirmed that the combination treatment was superior to the monotherapy treatments. 

Study Methods
Aged PDAPP transgenic mice (17-19 months) were randomized into the following five cohorts: 1) time zero control, 2) large and small molecule compound controls, 3) plaque-specific Aβ antibody (anti-Aβp3-x), 4) BACE inhibitor, and 5) Aβ antibody + BACE inhibitor. The aged mice were treated for four months with either a beta-secretase inhibitor or the N3pG beta-amyloid antibody, or the combination of the two drugs. Effectiveness of the treatments was determined by measuring the amount of beta-amyloid protein remaining in the brains of the mice.

About Alzheimer's Disease
Alzheimer's disease is a fatal illness that causes progressive decline in memory and other aspects of
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SOURCE Eli Lilly and Company
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