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Drug Reverses Alzheimer's in Lab Mice

  • Art Chimes

A cortex of a six-month-old mouse, after two weeks of bexarotene treatment. This image shows a reduction in staining, indicating the drug reduces the buildup of beta amyloid plaque.

A cortex of a six-month-old mouse, after two weeks of bexarotene treatment. This image shows a reduction in staining, indicating the drug reduces the buildup of beta amyloid plaque.

Cancer drug set to begin human tests soon

Researchers working with laboratory mice have stopped the progression of a condition found in the brain of Alzheimer's victims.

They've even reversed cognitive decline. But whether the discovery can translate to a treatment for humans with Alzheimer's is still a very big question

In Alzheimer's patients, a substance called beta amyloid builds up, and it's deposited as plaques on brain cells.

It's not that the body is producing too much beta amyloid. "The problem is in Alzheimer's disease, due to age-related inefficiencies in the ability to cut this peptide up and dispose of it, the peptide accumulates in the brain," explains Case Western Reserve University researcher Gary Landreth.

Clearing away beta amyloid is facilitated by a brain protein called apolipoprotein E (ApoE). An established anti-cancer drug bexarotene indirectly helps turn on the ApoE gene.

"So what this drug does is, it facilitates the normal clearing of the amyloid peptide. But then it also induces the brain's immune cells, or microglia, to eat up and dispose of the amyloid plaques, and the net effect is to clear amyloid from the brain."

Landreth tested the drug on mice that were genetically engineered to have an Alzheimer's-like condition. The mice that got the bexarotene drug regained some of the skills and behaviors lost to Alzheimer's. For example, normal mice shred up paper to build nests. But the untreated Alzheimer's mice don't. However, "if we put these guys on [the] drug for just 72 hours, they begin to build nests again. So...what the mice suggest is that in early stages of Alzheimer's Disease, the disease appears to be reversible."

Landreth cautions that what works in mice may not work at all in people, and that the mice in the study had the equivalent of early stage Alzheimer's, so that any reversal of Alzheimer's symptoms may not occur in more advanced cases.

Landreth and a colleague have applied for a patent to use bexarotene for Alzheimer's, and he doesn't hide his enthusiasm.

"This is kind of like being struck by lightning," he said. "We have a drug that is very safe, and importantly, it gets across the blood-brain barrier. That is, we can get it into the brain. And this is very rare."

Preliminary clinical trials in humans could begin in just a few weeks.

The research paper by Gary Landreth of the Case Western Reserve University School of Medicine in Cleveland, Ohio, and his colleagues is published online in Science.

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