Cancer drug may treat Alzheimer's

February 10, 2012
MyHealthNewsDaily

A cancer drug has succeeded in reversing Alzheimer's disease in its early stages in mice, according to a new study. The drug, bexarotene, is designed to reduce levels of amyloid beta, the protein whose presence in the brain has been most closely tied to the development of Alzheimer's.

In a new study, mice treated with bexarotene saw their amyloid beta levels drop 25 percent within six hours and, importantly, they showed a corresponding improvement in their cognitive function.

"The data we provide here really suggest that Alzheimer's could be, in the early stages, a reversible disease," said study author Paige Cramer, a doctoral student in neuroscience at Case Western Reserve School of Medicine.

The researchers used mice that had a mouse model of Alzheimer's disease. After the researchers administered varying doses of bexarotene, they measured levels of amyloid beta in the brain and tested the mice for their abilities in maze running, nest building, smell, and fear conditioning, which is a type of learning.

"They did a lot of different tests of learning and memory and they saw an effect on every single one of them," said Michael Sasner, a research scientist and associate director at the Jackson Laboratory in Bar Harbor, Maine.

Bexarotene is already approved by the Food and Drug Administration for the treatment of cutaneous T-cell lymphoma, a type of skin cancer, and so it may be able to proceed through clinical trials more quickly than drugs not already known to be safe to administer to people.The study appears in the Feb.10 issue of the journal Science.

Bexarotene is not the first attempted Alzheimer's treatment to target amyloid beta. But past research has aimed at removing the plaques that amyloid beta can form in the brain, which has not shown any effect on the disease itself.
The difference now, researchers say, is in a better understanding of amyloid beta and the various forms it can exist in. Rather than focusing on the plaques, researchers now think it is the active, soluble form of the protein that is at work in Alzheimer's.

While there are various views on the causes of Alzheimer's, "the predominant view right now is that it's the soluble forms of amyloid beta that are causing the impaired brain function," Cramer said. "Plaques are just sinks, just tombstones that gather amyloid beta."

Bexarotene works by promoting the production of another protein, called Apolipoprotein E, which binds to and clears amyloid beta from the brain.
"This paper lends a lot to the mechanism of how ApoE may be involved in Alzheimer's," Cramer said.

Hurdles remain
It remains to be seen whether the benefits of bexarotene in mice would translate to humans."Because we're using an FDA-approved drug, this allows us to translate these basic science findings to the clinic; that's our next goal," Cramer said.

Figuring out the correct dosing presents another challenge. Researchers found that in one case, giving bexarotene over several doses appeared to be less effective than giving it once. Cramer said the reason may be that the drug degrades itself within the body.

Cramer said she and Gary Landreth, the senior investigator on the study, hope to begin a preliminary trial this year, in which they will look for the same changes in beta amyloid levels in humans. If successful, the testing would move to clinical trials.

Bexarotene is currently sold as Targretin; patents on that drug will expire in April."There's a long way to go to prove this treatment in humans, but it seems like an exciting thing to follow up on," Sasner said.

http://www.foxnews.com/health/2012/02/10/cancer-drug-may-treat-alzheimers/