Cancer drug reverses Alzheimer’s

In a discovery the researchers describe as “unprecedented,” a cancer drug (bexarotene) already approved by the FDA has been shown to quickly reverse the pathological, cognitive and memory deficits caused by the onset of Alzheimer’s disease. Although only demonstrated in mice, the researchers believe the findings are compelling enough to warrant a speedy transition to clinical trials.

Researchers agree that Alzheimer’s disease arises in large part from the body’s inability to clear naturally-occurring amyloid beta from the brain. Previous studies have shown that the main cholesterol carrier in the brain, Apolipoprotein E (ApoE), facilitates the clearance of these amyloid beta proteins. Case Western Reserve University neuroscientist Gary Landreth decided to explore the effectiveness of bexarotene for increasing levels of ApoE. The elevation of brain ApoE levels speeds the clearance of amyloid beta from the brain by stimulating retinoid X receptors (RXR), which control how much ApoE is produced.

Reporting the findings in Science, Landreth said he was struck by the speed with which bexarotene improved memory deficits and behavior even as it also acted to reverse the pathology of Alzheimer’s disease. Within six hours of administering bexarotene, soluble amyloid levels fell by 25 percent; even more impressive, the effect lasted as long as three days. Finally, this shift was correlated with rapid improvement in a broad range of behaviors in three different mouse models of Alzheimer’s.

One example of the improved behaviors involved the nesting instinct of the mice. When Alzheimer’s-diseased mice encountered material suited for nesting – in this case, tissue paper – they did nothing to create a space to nest. This reaction demonstrated that they had lost the ability to associate the tissue paper with the opportunity to nest. Just 72 hours after the bexarotene treatment, however, the mice began to use the paper to make nests. Administration of the drug also improved the ability of the mice to sense and respond to odors.

Landreth added that the bexarotene treatment also worked quickly to stimulate the removal of amyloid plaques from the brain. The plaques are compacted aggregates of amyloid that form in the brain and are the hallmark of Alzheimer’s disease. Researchers found that more than half of the plaques had been cleared within 72 hours. Ultimately, the reduction totaled 75 percent. Previously, the best existing treatment for Alzheimer’s disease in mice required several months to reduce plaque in the brain.

While Landreth calls the discovery “exciting,” he cautions that the drug has only been tested in mouse models of the disease. “Our next objective is to ascertain if it acts similarly in humans. We are at an early stage in translating this basic science discovery into a treatment,” he concluded.

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Source: Case Western Reserve University

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