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Cancer Drug Today, Alzheimer's Drug Tomorrow? Hopeful Results in Mouse Study

80beatsBy Sarah ZhangFeb 13, 2012 5:17 PM

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Amyloid beta deposits in brain of Alzheimer's patient.

What's the News: A drug used to cure skin cancer is also a possible treatment for Alzheimer's, according to a new study in Science

. The drug not only reduced levels of amyloid beta

---a protein whose elevated levels are a hallmark of the disease---but also reversed cognitive decline. In mice, dramatic effects were evident after just 72 hours. How the Heck:

  • Based on known molecular pathways, the researchers thought that the skin cancer drug bexarotene could enhance expression of a gene called apoEapoE activates the immune system to break down amyloid beta, and mutations in the apoE gene are a major risk factor for Alzheimer's.

  • Turns out the researchers were right. Mice with genetic mutations that make them prone to the disease are the standard model for Alzheimer's research. When these mice were treated with bexarotene, macrophages in their brain gobbled up amyloid beta, and the levels of amyloid beta fell by 40% in just 72 hours.

  • Molecular changes are good and all, but an effective drug for Alzheimer's also has to treat the behavioral symptoms. Bexarotene actually reversed cognitive deficits. The team put treated mice through standard memory tests, including fear conditioning, the Morris water maze, and odor habituation. Bexarotene improved their performance in all of them.

Not So Fast: 

  • Just because something works in mice doesn't mean it will work in humans. According to a Trends in Neuroscience review, there have been 300 reports of treatments that ameliorate Alzheimer's in mice since 1995. But the number of cures in humans in 2012: Zero.

  • That's because the brain of a 6-month-old mouse with genetic mutations is an imperfect model for that of an 80-year-old Alzheimer's patient. No single mouse recapitulates all the symptoms of human Alzheimer's---for example: some "Alzheimer's mice" will have amyloid beta deposits but no cognitive deficits. This study actually used three different strains of mutant mice, but that's three out of dozens available. The exact cause and progression of Alzheimer's is still mysterious, so finding a cure is difficult when we haven't even unwrapped the problem.

  • Even if bexarotene works in humans, a miracle cure it isn't. It wouldn't be of much help to patients with advanced Alzheimer's, whose dementia is the result of neurons being killed in what scientists think is a process trigged by amyloid beta. Bexarotene can go as far as reducing levels of amyloid beta, but it can't reverse cell death.

The Future Holds: 

Reference: Cramer, et al. ApoE-Directed Therapeutics Rapidly Clear Beta-Amyloid and Reverse Deficits in AD Mouse Models. Science (9 February 2012) DOI: 10.1126/science.1217697

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