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New model suggests feared side effect of Alzheimer's drugs is unlikely
Date:6/17/2010

The first trial of a new model for testing Alzheimer's treatments has reassured researchers that a promising class of drugs does not exacerbate the disease if treatment is interrupted.

Scientists at Washington University School of Medicine in St. Louis and Merck & Co. Inc studied the effects of a class of drugs known as gamma secretase inhibitors. Researchers had worried that these drugs might cause a build-up of proteins linked to Alzheimer's disease and that this build-up could be unleashed in a surge when patients went off the medications. But the new study suggests that they do not.

"This is important because it eases some concerns that have been raised about this potentially useful class of medications," says senior author Randall Bateman, MD, a Washington University neurologist who treats patients at Barnes-Jewish Hospital.

The findings appeared recently in The Journal of Neuroscience.

Gamma secretase inhibitors block proteins involved in the creation of amyloid beta, the main ingredient of Alzheimer's plaques. Patients cannot continuously take these drugs because nonstop inhibition of the gamma secretase enzyme has harmful side effects. One study had revealed that when physicians temporarily halted used of the inhibitors in humans, amyloid beta levels in the blood surged. An animal study suggested cessation of treatment also led to an amyloid beta increase in the brain. Researchers have been watching for similar effects in current human clinical trials of gamma secretase inhibitors.

The new study used a technique for measuring production and clearance of amyloid beta developed by Bateman and his colleagues at Washington University. It was the first time stable-isotope-labeling kinetics (SILK) was used in primates.

In a preliminary assessment of normal amyloid beta production and clearance rates, scientists found that the amyloid beta turnover in the subjects, a group of rhesus macaques, was 10
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Contact: Michael C. Purdy
purdym@wustl.edu
314-286-0122
Washington University School of Medicine
Source:Eurekalert

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