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Cancer drugs and Alzheimer's, Oh my!

  1. Feb 9, 2012 #1


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    Alerted to this from a friend who is an alumni of Case
    Very excited to read the article in Science, when it comes out--Granted this is of course a press-release and prone to a certain kind of hype. That said still looks promising, I'm not aware of any potential treatments yet that have had such a profound effect on mouse models. Of course this is in mouse models and possibly won't translate well into humans--Though that this is an on the market FDA approved drug, I think provides some hope for good translation.

    Edit: The article is available online already;

    Will give a read tomorrow with my thoughts after this terrible [strike]hell[/strike] exam week is over!
    Last edited: Feb 9, 2012
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  3. Feb 9, 2012 #2


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    The article was published today online on the Science website:

    Cramer et al. 2012. ApoE-Directed Therapeutics Rapidly Clear β-Amyloid and Reverse Deficits in AD Mouse Models. Science. doi:10.1126/science.1217697

    This research is definitely promising, and because bexarotene is already a drug approved for other uses, clinical testing of the drug should go quickly.

    There is, however, reason to believe that this will not be a magic bullet for Alzheimer's. As the article mentions, mutations to ApoE are major risk factors for Alzheimer's. If many patients with Alzheimer's have non-functional forms of ApoE, it is unclear whether boosting the expression ApoE using bexarotene will facilitate clearance of the amyloid plaques in these individuals. After all, if the protein is not working correctly, having more of it around may not fully correct the underlying defect with the protein.

    Furthermore, it's important to remember that mouse models of diseases are not perfect. Cramer et al. use APP/PS2 mice which carry mutations in the amyloid beta precursor protein and presenilin 2, causing the mice to develop the amyloid beta plaques that many believe are responsible for Alzheimer's disease. However, research also suggests that dysfunction of another protein tau may also be an important driver of Alzheimer's disease. Unfortunately, the APP/PS2 mice used in this study do not recapitulate the tauopathies seen in human Alzheimer's cases, so it is unclear whether the drug can correct problems associated with dysfunctional tau as well. Furthermore, although the APP/PS2 mice suffer cognitive decline, neurons in the mouse model do not die off as they do in human Alzheimer's, which could explain why the researchers could so easily reverse the cognitive and memory defects.

    Nevertheless, this study provides a very promising lead for a potential therapy for Alzheimer's disease.

    [edit: Here's a nice article from Scientific American which talks about the study as well as some of the criticisms I mentioned above:
    http://www.scientificamerican.com/article.cfm?id=alzheimers-disease-sympto ]
    Last edited: Feb 10, 2012
  4. Feb 10, 2012 #3


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    I'm short on time so haven't read the paper yet but this comment I definitely agree with. The news last night (C4) opened with "scientists in America have Alzhiemer's breakthrough!" they went on for ages before they even bothered to mention it was in a mouse. Then they interviews people with Alzhiemer's and talked about how their lives are etc which I can't condone at all. All they've done is get people's hopes up for something which only has potential at the moment (how many times have we cured various diseases in mice only for it to not work in humans?)
    Best of luck bobze :biggrin:
  5. May 27, 2013 #4


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    A year ago we were wondering whether the results of this study would hold up in humans. Apparently, the results don't even seem to hold up in mice!


    For the actual papers see https://www.sciencemag.org/content/340/6135.toc#TechnicalComments
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