Dimebon's Action May Challenge Amyloid Theory

By Sullivan, Michele G. | Clinical Psychiatry News, November 2009 | Go to article overview

Dimebon's Action May Challenge Amyloid Theory


Sullivan, Michele G., Clinical Psychiatry News


VIENNA -- Dimebon-the abandoned Russian antihistamine that burst onto the Alzheimer's study scene with the only positive clinical data of 2008--may throw yet another curve ball into a research world that for years has focused almost entirely on the amyloid hypothesis.

Rather than lowering amyloid beta (Abeta) levels, as two failed investigational drugs--tramiprosate and taren-flurbil--have attempted, dimebon appears to almost immediately increase them, raising Abeta by as much as 200% in three mouse models of Alzheimer's disease (AD), Dr. Samuel Gandy reported at the International Conference on Alzheimer's Disease.

While preliminary, the findings--combined with the nearly unprecedented cognitive benefit dimebon conferred in its phase II trial--could be enough to dethrone the long-reigning amyloid hypothesis, according to Mark A. Smith, Ph.D., an Alzheimer's researcher. "This drug is clearly not targeting amyloid, but increasing it acutely," said Dr. Smith of Case Western Reserve University, Cleveland. "If you believe the dogma, therefore, you should believe that this increase will cause Alzheimer's. These results question that dogma. If this holds up, it could be enough to wound the amyloid theory, potentially mortally."

Dimebon's 2008 phase II study found that patients with mild to moderate AD who took the drug for 12 months gained about 2 points on the Alzheimer's Disease Assessment Scale-Cognition (ADAS-cog), while those taking placebo declined almost 6 points from baseline (Lancet 2008;372:207-15). A 6-month open-label extension trial found similarly positive results. Patients who completed a full 18 months of dimebon continued to show benefit on ADAS-cog. Former placebo patients who crossed over to dimebon stabilized their cognitive decline.

Dr. Gandy of the Mount Sinai School of Medicine, New York, investigated the drug's effect on amyloid in three models of the disease: cultured nerve cells, isolated synaptic terminals, and brains from mice that overexpress human amyloid. "In every single system dimebon stimulated amyloid secretion," Dr. Gandy said in an interview. "The levels of the amyloid peptides in the interstitial brain fluid roughly doubled whenever the drug was given. If we think about the increased risk of Alzheimer's in Down syndrome patients who have a 50% increase in amyloid, this acute increase with dimebon could be significant over a period of many years of prescribed use."

Dr. Gandy noted that similar results were obtained by John Cirrito, Ph.D., and Dr. David Holtzman of Washington University, St. Louis, who collaborated with him in studying the brains of freely moving transgenic mice that overexpress human Abeta. …

The rest of this article is only available to active members of Questia

Already a member? Log in now.

Notes for this article

Add a new note
If you are trying to select text to create highlights or citations, remember that you must now click or tap on the first word, and then click or tap on the last word.
One moment ...
Default project is now your active project.
Project items
Notes
Cite this article

Cited article

Style
Citations are available only to our active members.
Buy instant access to cite pages or passages in MLA 8, MLA 7, APA and Chicago citation styles.

(Einhorn, 1992, p. 25)

(Einhorn 25)

(Einhorn 25)

1. Lois J. Einhorn, Abraham Lincoln, the Orator: Penetrating the Lincoln Legend (Westport, CT: Greenwood Press, 1992), 25, http://www.questia.com/read/27419298.

Note: primary sources have slightly different requirements for citation. Please see these guidelines for more information.

Cited article

Dimebon's Action May Challenge Amyloid Theory
Settings

Settings

Typeface
Text size Smaller Larger Reset View mode
Search within

Search within this article

Look up

Look up a word

  • Dictionary
  • Thesaurus
Please submit a word or phrase above.
Print this page

Print this page

Why can't I print more than one page at a time?

Help
Full screen
Items saved from this article
  • Highlights & Notes
  • Citations
Some of your highlights are legacy items.

Highlights saved before July 30, 2012 will not be displayed on their respective source pages.

You can easily re-create the highlights by opening the book page or article, selecting the text, and clicking “Highlight.”

matching results for page

    Questia reader help

    How to highlight and cite specific passages

    1. Click or tap the first word you want to select.
    2. Click or tap the last word you want to select, and you’ll see everything in between get selected.
    3. You’ll then get a menu of options like creating a highlight or a citation from that passage of text.

    OK, got it!

    Cited passage

    Style
    Citations are available only to our active members.
    Buy instant access to cite pages or passages in MLA 8, MLA 7, APA and Chicago citation styles.

    "Portraying himself as an honest, ordinary person helped Lincoln identify with his audiences." (Einhorn, 1992, p. 25).

    "Portraying himself as an honest, ordinary person helped Lincoln identify with his audiences." (Einhorn 25)

    "Portraying himself as an honest, ordinary person helped Lincoln identify with his audiences." (Einhorn 25)

    "Portraying himself as an honest, ordinary person helped Lincoln identify with his audiences."1

    1. Lois J. Einhorn, Abraham Lincoln, the Orator: Penetrating the Lincoln Legend (Westport, CT: Greenwood Press, 1992), 25, http://www.questia.com/read/27419298.

    Cited passage

    Thanks for trying Questia!

    Please continue trying out our research tools, but please note, full functionality is available only to our active members.

    Your work will be lost once you leave this Web page.

    Buy instant access to save your work.

    Already a member? Log in now.

    Search by... Author
    Show... All Results Primary Sources Peer-reviewed

    Oops!

    An unknown error has occurred. Please click the button below to reload the page. If the problem persists, please try again in a little while.