Alzheimer's: cancer drug loosens protein balls

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Washington (dapd). US researchers may have made an important breakthrough in the fight against Alzheimer's disease. A drug approved for use against cancer has reversed Alzheimer's symptoms in mice.The active ingredient bexarotene removed the cell-destroying protein deposits in the animals' brains within hours and thus prevented the further breakdown of brain mass. At the same time, the remedy also degrade 75 percent of the dissolved protein compounds that impair communication between the brain cells in Alzheimer's disease. The previously severely disturbed behavior and memory of the mice returned to normal very quickly, the researchers report in the journal Science. (doi: 10.1126 / science.1217697)

"This is an unprecedented find," says lead author Paige Cramer of the Case Western Reserve School of Medicine in Cleveland. A similarly quick and effective effect on behavior and cognitive failures in Alzheimer's had not been observed before. So far, the best known Alzheimer's drug takes months to reduce the protein plaques in the brain.

Scientists confident of human application

It is not yet clear whether bexarotene is equally effective against Alzheimer's in humans, the researchers emphasize. But the results in mice are very promising. Since the active ingredient has already been approved as a cancer drug for humans, it is already known that it can be used safely and without serious side effects. The scientists hope that this could greatly accelerate the start of clinical trials with humans.

"There is much evidence that this approach could be successful in treating Alzheimer's disease," said co-author Daniel Wesson of Case Western Reserve University. Above all, the broad effect on various functional disorders of the brain is promising.

Cancer drug acts on apolipoprotein E production

The active ingredient bexarotene has also been approved as a cancer drug in Germany since 2002. It is mainly used against certain types of lymph gland cancer. The agent can penetrate the blood-brain barrier and therefore also exert its effect directly in the brain.

It was already known that bexarotene acts on a docking point in the cell nucleus, which among other things controls the production of apolipoprotein E (ApoE). The ApoE protein plays an important role in the brain as “garbage disposal” for the harmful protein plaques. In Alzheimer's patients, the breakdown of these amyloid proteins is disturbed, which is why they accumulate in the brain. The researchers have now demonstrated in mice for the first time that bexarotene can compensate for this deficiency by increasing ApoE production.

Skills regained shortly after treatment

The experiments not only showed a rapid reduction in amyloid plaques in the animals' brains. The mice's Alzheimer's symptoms also improved. Just 72 hours after the first treatment, the mice learned to build a nest out of scraps of paper - a skill they had previously lost due to Alzheimer's. They also coped with memory tests as well as healthy mice.

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