Study Finds 'Serious Problems' With 2012 Alzheimer's 'Breakthrough'

Initial study suggested a cancer drug could reverse effects of Alzheimer's in mice.

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Last year, a study published in the journal Science suggested there had been a major breakthrough in the treatment of Alzheimer's disease.

Replications of the study, which suggested a cancer drug already approved by the FDA could reduce the buildup of Alzheimer's-causing plaques in the brain, have found "serious problems" with the initial study, and the study was unable to be confirmed by independent researchers in nine different laboratories.

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Published in February 2012, the original study found that the drug bexarotene, known popularly as Targretin, could reduce the buildup of beta amyloid plaques in the brains of mice.

In that study, plaques were reduced by as much as 50 percent within three days and 75 percent within three weeks. Targretin is typically used to treat T-cell lymphoma, a rare type of skin cancer. The initial study was undertaken by scientists at Case Western Reserve University School of Medicine and the Hope Center for Neurological Disorders.

Perhaps most alarmingly, the drug, which has severe side effects, has been – at least anecdotally – prescribed to Alzheimer's patients off-label and is quickly headed towards a Phase I human clinical trial.

Soon after the original paper was published, an expert on the popular TV show Dr. Oz plugged the drug for use in Alzheimer's patients. From then, people began demanding their doctor prescribe it for their loved ones with the disease, according to Sangram Sisodia, a neuroscience professor at the University of Chicago and one of the authors of the new study that refutes the original.

"It's FDA approved so you can get it, but it's extremely toxic. When we treat mice with them, within a week their liver is twice its normal weight, you get skin lesions [and] are lethargic," he says. "It's a cancer drug, what do you expect?"

Sisodia says when the report was initially released, many in the field were skeptical, but cautiously hoped an Alzheimer's breakthrough had been achieved.

"I think many of us were floored by the results but wanted confirmation. As academics, we try to study things we think are really important, and this result was very important," he says. "But the results were not to be so."

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He and independent researchers at Northwestern University, Massachusetts General Hospital, Washington University in St. Louis and the University of Tubingen in Germany all performed the same experiment and found there was no reduction in mice's beta amyloid plaques after treatment with bexarotene.

"Something happened in that initial report – either something technically or otherwise, which we can't put our hands on at this point in time," Sisodia says. "Something is seriously wrong."

In a response to the latest report, the original team admitted there "is a clear discrepancy between the outcomes reported by us and [the new ones], and it is important to understand their basis."

The team stood by their study and claimed that the side effects of Targretin are overstated. They also said that plaque is "functionally unrelated to improved cognition and memory elicited by bexarotene."

Sisodia says the team has shared their data with the team that is planning a clinical trial, but that the Alzheimer's Drug Discovery Foundation plans to go ahead with it anyway.

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"They knew our study was coming out, saw our papers and our written commentary," Sisodia says. "They already know our data, but they're going ahead with it anyway. I can't believe it."

Requests for comment from U.S. News to both the Alzheimer's Drug Discovery Foundation and Valeant Pharmaceuticals, the company that manufactures Targretin, were not immediately returned.

A press release announcing the Phase I trial in April says the trial is "set to commence later this year [and] will evaluate at least 12 healthy human subjects."

"This clinical trial will evaluate if bexarotene can affect critical biomarkers in the human brain, a key step in the quest to develop effective and safe treatments for Alzheimer's patients," Howard Fillit, executive director of the Alzheimer's Drug Discovery Foundation, said in the statement.