Asthma Drug Blocks Plaque Formation in Mouse Model of Alzheimer's Disease

The drug zileuton, which is used to treat asthma, has been shown to reduce formation of amyloid plaques in an Alzheimer's disease mouse model.

Investigators at Temple University (Philadelphia, PA, USA) had found previously that plaque formation required the activity of the enzyme gamma secretase and that gamma secretase was regulated in turn by another enzyme, 5-lipoxygenase. The latter enzyme is inhibited by zileuton, and in the current study, the investigators examined what effect the drug might have on amyloid plaque formation in the Tg2576 transgenic mouse model of Alzheimer's disease.

They reported in the April 2011 issue of the American Journal of Pathology that amyloid-beta deposition in the brains of mice receiving zileuton was significantly reduced when compared with control Tg2576 mice receiving a placebo. This reduction was associated with a similar decrease in brain amyloid-beta peptides levels. Zileuton treatment did not induce any change in the steady state levels of amyloid-beta precursor protein, but rather it resulted in a significant reduction in levels of the four components of the gamma secretase complex. These findings were confirmed by in vitro studies that showed that zileuton prevented amyloid-beta formation by modulating gamma secretase-complex levels.

Zileuton has already been approved by the [US] FDA (Food and Drugs Administration) for treatment of asthma through 5-lipoxygenase inhibition. Blocking this enzyme has not been associated with overt toxicity and it was well tolerated by patients.

"This drug is already on the market and, most importantly, is already FDA-approved, so you do not need to go through an intense drug discovery process,” said senior author Dr. Domenico Praticò, associate professor of pharmacology at Temple University. "So we could quickly begin a clinical trial to determine if there is a new application for this drug against a disease where there is currently nothing.”

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