Promising Alzheimer’s Drug Fails In Second Test Round
May 24, 2013

Promising Alzheimer’s Drug Bombs In Second Round Of Trials

Brett Smith for - Your Universe Online

While the recent failure of a potential Alzheimer´s disease treatment is bad news for patients, it serves as an important reminder of the importance of thorough pre-clinical testing of experimental drugs before beginning human trials.

According to a group of University of Florida researchers, tests of the anti-cancer drug bexarotene failed to stop the formation of the amyloid brain plaques that are associated with Alzheimer´s disease, conflicting with the results of an identical 2012 study.

“We wanted to repeat the study to see if we could build on it, and we couldn´t,” said David Borchelt, a professor of“¯neuroscience“¯at UF. “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,” he added.

The latest study, which was published in the journal Science, focused of a 2012 article in the same journal that claimed orally-administered bexarotene had mitigated Alzheimer´s-like symptoms in mice with amyloid plaques.

Co-author“¯Kevin Felsenstein, an associate professor of neuroscience at UF, said the results of the first study were surprising considering the amount of research that had failed to find a successful treatment for disrupting the plaques.

The first 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.

However, contrary to the 2012 study, Felsenstein and his colleagues weren´t able to reduce to levels or size of amyloid plaques in lab mice brains using orally-administered bexarotene.

“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.”

Using mice that were the same age as those in the previous study, the researchers confirmed that the drug had reached its target genes in the mice by observing elevated levels of a protein called apolipoprotein E. This protein is though to prevent the buildup of amyloid plaques in healthy individuals who do not have symptoms of Alzheimer´s disease.

However, the elevated protein levels seemed to have no effect on the amyloid plaques in the UF study. After seven days of treatment, the size and number of plaques remained the same. Two additional teams of researchers were also unable to repeat the breakdown of amyloid plaques reported in the first study.

Felsenstein noted that his team is not questioning the integrity of the researchers who performed the 2012 study.

“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 said.