Research: Anti-cancer drug tested as possible treatment for Alzheimer's disease proved ineffective

An anti-cancer drug about to be tested in a clinical trial by a biomedical company in Ohio as a possible treatment for Alzheimer's disease has failed to work with the same type of brain plaques that plague Alzheimer's patients, according to results of a study by University of Florida researchers.

David Borchelt, Ph.D., a professor of neuroscience affiliated with the Evelyn F. and William L. McKnight Brain Institute of the University of Florida, emphasized the importance of verifying promising research results before investing in clinical studies or testing potential therapies in people. Bexarotene has known side effects that include effects on the liver, blood and other metabolic systems.

"We wanted to repeat the study to see if we could build on it, and we couldn't," he said. "We thought it was important that something like this, which got a lot of publicity and patients were immediately looking to try to get access to this drug, that it was important to publish the fact that we couldn't reproduce the most exciting part of the study. Maybe there should be some caution going forward in regard to patients."

Borchelt and Kevin Felsenstein, Ph.D., an associate professor of neuroscience, said a drug called bexarotene that their team orally administered to mice did not reduce amyloid plaques, waxy buildups on the brain that are a key culprit in Alzheimer's disease. Their findings will be published in the May 24, 2013 issue of the journal Science magazine, with two additional articles detailing similar results from other researchers.

The research follows up on a 2012 Science article that claimed bexarotene had reversed Alzheimer's-like symptoms in mice afflicted with the plaques. Authors of that study also administered the drug orally.

The paper "indicated that with as little as three days of treatment, they basically cleared the amyloid deposits from these animals, as well as restored cognitive abilities," Felsenstein said of the 2012 paper.

He said the results of the original study were surprising, given decades of research that had failed to find a therapy successful in dismantling amyloid plaques.

"We can shut down the production of amyloid in these animal models and the deposits in these animal models don't disappear," Felsenstein said. "These deposits have been described by some as cement, and it will take a lot to get rid of them. The fact that something could actually make them disappear in literally a couple of days is - again - very remarkable."

Interested to see how bexarotene might work to break down amyloid plaques, Felsenstein and Borchelt selected mice approximately the same age as those used in the 2012 study and orally administered the drug to the mice. Tests confirmed the drug had reached its target genes in the mice, and that it elevated levels of a protein called apolipoprotein E. Some scientists believe one of the forms of this protein may prevent the buildup of amyloid brain plaques in people who don't have Alzheimer's disease.

But elevated levels of the protein in the mice studied by UF researchers seemed to have no effect on the animals' amyloid plaques. Samples taken after seven days of treatment with bexarotene showed no significant difference in the number or size of plaques in the animals' brains. Two teams of researchers from other institutions also were unable to replicate the breakdown of amyloid plaques.

Felsenstein emphasized that his team does not claim the previous study indicating bexarotene's effectiveness is "totally wrong."

"We're just saying right now it's extremely difficult to replicate and there may be little nuances, that there's something that we don't quite understand," he added. Felsenstein and Borchelt both work at UF's Center for Translational Research in Neurodegenerative Disease.

The other two research groups who published papers in this week's journal Science were led by Bart De Strooper, Ph.D., M.D., director of the VIB Center for the Biology of Disease in Belgium, and Sangram S. Sisodia, Ph.D., director of the Center for Molecular Neurobiology at the University of Chicago.