Mice in the early stage of Alzheimer's disease had brain abnormalities reversed and mental function restored when they were given low doses of a rarely used cancer drug.
The drug, bexarotene, stimulated removal of beta-amyloid, a brain substance that can lead to Alzheimer's dementia.
After treatment, the animals fared better in tests of memory and social behavior, according to a study published online Thursday by the journal Science.
The findings were dramatic, but their relevance to people is unknown. Many chemical compounds that looked promising in mice have flopped in humans. And human clinical studies could easily take five or six years.
Still, the fact that the Food and Drug Administration already has approved bexarotene for human use should speed things along.
"We've got to work fast and we have got to be right. We can't screw this up," said Gary E. Landreth, a neuroscientist at Case Western Reserve University School of Medicine who headed up the experiment.
As with any highly publicized mouse study, researchers fear people might seek out the drug before it's fully evaluated. A few days ago Landreth got a call from a physician in another city. A patient had heard about the study and asked for a prescription for bexarotene.
University of South Florida professor Huntington Potter said further exploration of the drug is needed to sort out which biological mechanisms are creating positive changes in the brain.
But the results definitely are promising, he said.
"This is better than most mouse studies, much better,'' said Potter, who directs the Florida Alzheimer's Research Center. "It's a beautiful piece of work.''
About 5.4 million Americans have Alzheimer's disease, which is the leading cause of dementia. About 5 percent of people in their late 60s suffer from it, and possibly half of people in their late 80s.
The Case Western experiments were done by Paige E. Cramer, a graduate student in Landreth's lab. The target was beta-amyloid, a protein that accumulates in watery liquid between brain cells — even in normal people.
People with Alzheimer's Disease have higher levels of beta-amyloid, and when it binds together in string-like fashion, it interferes with how neurons communicate with each other.
The beta-amyloid strings also clump together in Brillo pad-like "plaques.''
Eventually, other things happen and neurons start to die.
Lab mice are bred to develop some — but not all — of these symptoms. They also lose cognitive function. Since researchers can dissect their brains to find out what is going on, mice have become the gold standard for testing Alzheimer's treatments.
Bexarotene is a compound chemically related to Vitamin A and sold under the trade name Targretin. It is primarily used to treat cutaneous T-cell lymphoma, a disease diagnosed in about 3,000 Americans a year.
The Case Western researchers discovered that bexarotene also stimulates production of a protein called apoE, which breaks down beta-amyloid.
Within a few days of a single dose of bexarotene, beta-amyloid levels in the mice brains brain fell by 25 percent.
The drug also enhanced the capabilities of microglia cells, little foot soldiers that gobble up beta-amyloid, both in its toxic string form and in its plaque form. Under the microscope, the mice microglia were stuffed with beta-amyloid.
To cap it off, the mice performed just was well as normal mice on cognitive tests, while lab mates who didn't get the drug worsened.
One interesting facet was what happened with the clumped up amyloid plaques.
In early days of Alzheimer's research, scientists thought plaques themselves caused the disease. Many now believe the plaques are a by-product, not a cause.
The Case Western study tends to support the newer theory. The plaques fell by 75 percent over a few weeks, then reaccumulated.
But the liquid-form beta-amyloid did not reaccumulate, nor did the mice get stupid again.
"It appears that the measurable activity of the brain is not affected by the presence of the plaques,'' Landreth said. "I think that is a really interesting finding that will stimulate a lot of new science."
USF's Potter speculated that bexarotene's ability to enhance the microglia that consume beta-amyloid may eventually prove more important than boosting the apoE protein that breaks down beta-amyloid into harmless amino acids.
USF already is conducting human clinical trials on a protein called GM-CSF, which also stimulates microglia production. With more funding, Potter said, those trials could expect some results in a year or so.
Tampa Bay Times reporter Stephen Nohlgren and the Washington Post contributed to this report.