By Julie Steenhuysen
CHICAGO (Reuters) - U.S. scientists say a dramatic result last year suggesting that a cancer drug already approved by U.S. regulators could quickly clear out Alzheimer's plaques in mice was too good to be true.
The study, published last year in the journal Science, showed the skin cancer drug bexarotene cut the amount of an Alzheimer's-linked protein called beta amyloid by half in three days. It also reversed Alzheimer's symptoms, restoring a sense of smell in treated mice and allowing them to resume nest building activities.
The news sent patients clamoring for the drug, and some doctors began prescribing it, even though it had not been tested in people with Alzheimer's. But researchers at several U.S. centers reported in the same journal on Thursday that they were unable to reproduce the most dramatic aspects of the findings in their own labs.
Gary Landreth and colleagues at Case Western Reserve University in Cleveland, the scientists behind the original research, say the drug still has merit, noting that the latest studies confirmed other aspects of the research showing the drug cleared out soluble forms of beta amyloid from the brain.
Scientists say the controversy is a stark reminder of the need for studies to be replicated by other labs, and it underscores the desperation of Alzheimer's sufferers to find effective treatments for the fatal, brain-wasting disease that affects 5 million Americans and 38 million people worldwide.
"I was a fan of the original study," said Dr. Samuel Gandy, associate director of the Mount Sinai Alzheimer's Disease Research Center in New York, who was not involved in any of the studies.
"It was very dramatic. It cut plaque loads by three-quarters over less than a week. No one had ever seen anything like it before."
Gandy has had several patients asking for the treatment. Although U.S. doctors are free to prescribe any treatment approved by the FDA, Gandy said the drug has substantial liver toxicity and requires very careful monitoring.
"I have universally declined and advised others to decline."
There is no cure or effective treatment for Alzheimer's disease, a progressive form of dementia steadily destroys brain cells, and several large companies have failed in late-stage clinical trials, with the most recent being Baxter International's drug Gammagard earlier this month.
Sangram Sisodia, a professor of neuroscience at the University of Chicago, said he and his colleagues were curious about the initial report in 2012.
"It was hot stuff. It was the new miracle drug for Alzheimer's. Even Doctor Oz proclaimed such," said Sisodia, referring to a popular FOX TV show hosted by Dr. Mehmet Oz.
"People were clamoring for this drug after he went on TV and was pushing it."
Sisodia said he and fellow Alzheimer's colleagues, who included Dr. Rudolph Tanzi of Massachusetts General Hospital in Boston and Dr. David Holtzman of Washington University School of Medicine, wanted to see if the stunning results could be replicated in their own labs, a standard part of the scientific process.
Researchers failed to see any effects on Alzheimer's plaques in three strains of mice that were treated with bexarotene.
"There is absolutely no reduction in amyloid levels in the brains of mice treated with this compound," said Sisodia of his group's efforts, which were published as a technical comment in the journal Science. Teams at the University of Florida and researchers at the University of Leuven in Belgium published similar findings in the same journal.
TEMPEST IN TEAPOT
Landreth, who has formed a company to study the compound, says the teams are all focusing on the dramatic changes in solid forms of beta amyloid reported in the study, which, despite the press it got, was not the study's main finding.
"We concluded that plaques didn't matter and said so explicitly. As we look at the comments we just don't get it," he said. Landreth can't fully explain why the teams were unable to confirm the findings on plaque.
Even so, he said the latest studies do confirm some of his main findings which suggest the treatment significantly reduces the amount of soluble forms of beta amyloid that float in interstitial fluid that bathes brain cells.
Some studies have suggested that this soluble form of beta amyloid is the more toxic form of the protein, and removing it could offer significant benefits to patients.
A fourth study by a team at the University of Pittsburgh appears to back up his assertion.
The team was able to verify that the drug bexarotene significantly improves cognitive deficits in mice with gene mutations linked to human Alzheimer's. And it confirmed that the compound decreased small bits of toxic beta amyloid in the fluid that surrounds brain cells. But it, too, failed to show a reduction in amyloid plaques.
"We believe these findings make a solid case for continued exploration of bexarotene as a therapeutic treatment for Alzheimer's disease," Dr. Rada Koldamova, who led the study, also published in Science, said in a statement.
Landreth says the current "scientific tempest in a teapot" does not deter his plans to study bexarotene in people.
His company, called ReXceptor Inc., plans to start early stage trials in a group of six healthy adults within the next few months. The team hopes to prove the drug works by flushing soluble bits of the toxic protein out of the brain.
"We should have an outcome by Christmas," Landreth said.
(Reporting by Julie Steenhuysen; Editing by Leslie Gevirtz)