Featured Research

from universities, journals, and other organizations

Multiple research teams unable to confirm high-profile Alzheimer's study

Date:
May 23, 2013
Source:
University of Chicago Medical Center
Summary:
Teams of highly respected Alzheimer’s researchers failed to replicate what appeared to be breakthrough results for the treatment of this brain disease when they were published last year in the journal Science.

Teams of highly respected Alzheimer's researchers failed to replicate what appeared to be breakthrough results for the treatment of this brain disease when they were published last year in the journal Science.

Related Articles


Those results, presented online Feb. 9, 2012, suggested that the drug bexarotene (marketed as Targretin®) could rapidly reverse the buildup of beta amyloid plaques (Aβ) -- a pathological hallmark of Alzheimer's disease -- in the brains of mice. According to the authors of the 2012 report, drug treatment quickly removed most of the plaques and brought rapid reversal of the pathological, cognitive and memory deficits related to the onset of Alzheimer's.

However, the new reports from extensive and carefully controlled studies did not show any reduction in the number of plaques or total area occupied by the plaques during or after treatment. These results are described in three "technical comments" -- one of which comes from researchers at the University of Chicago, Northwestern University, Massachusetts General Hospital, Washington University in St Louis and University of Tubingen in Germany -- to be published in the May 24, 2013, issue of Science.

"The drug has no impact on plaque burden in three strains that exhibit Aβ amyloidosis," according to that group's comment. "We have failed to support earlier findings by Cramer et al that Targretin is efficacious in reducing plaque burden in transgenic mouse models of cerebral Aβ deposition."

Comment co-author Sangram Sisodia, PhD, professor of neurosciences at the University of Chicago, said he and his colleagues were curious about the initial report in 2012.

"We were surprised and excited, even stunned, when we first saw these results presented at a small conference," said Sisodia. "The mechanism of action made some sense, but the assertion that they could reduce the areas of plaque by 50 percent within three days, and by 75 percent in two weeks, seemed too good to be true."

"We all went back to our labs and tried to confirm these promising findings," Sisodia added. "We repeated the initial experiments -- a standard process in science. Combined results are really important in this field. None of us found anything like what they described in the 2012 paper."

The researchers found no effects on plaque burden in three different strains of mice that were treated with bexarotene.

The discrepancy, besides being disappointing, also raises concerns about patient safety. The Food and Drug Administration approved bexarotene in December 1999 for a very specific use: treatment of refractory cutaneous T-cell lymphoma, a type of skin cancer. Once approved, the drug became legally available by prescription for "off-label" uses as well.

"Anecdotally, we have all heard that physicians are treating their Alzheimer's patients with bexarotene, a cancer drug with severe side effects," said co-author Robert Vassar, PhD, professor of cell and molecular biology at Northwestern University Feinberg School of Medicine. "This practice should be ended immediately, given the failure of three independent research groups to replicate the plaque-lowering effects of bexarotene."

Bexarotene has never been tested as a treatment for Alzheimer's disease in humans, not even to determine the optimal dose or duration of treatment. This drug has significant side effects, including major blood-lipid abnormalities, pancreatitis, liver function test abnormalities, thyroid axis alterations, leucopenia, headaches, fatigue, weight gain, depression, nausea, vomiting, constipation and rash.

The two other technical comments came from research teams led by Kevin Felsenstein, Todd Golde, David Borchelt and colleagues at the University of Florida and by Bart DeStrooper and colleagues at the University of Leuven, Belgium.

There is no cure or effective treatment for Alzheimer's disease, which is a progressive type of dementia that occurs when nerve cells in the brain die. When Alzheimer's was first identified in 1906, it was considered a rare disorder. Today, Alzheimer's is the most common cause of dementia. An estimated 5.3 million Americans have the disease.

This work was supported by the Cure Alzheimer's Fund. Additional authors include Karthikeyan Veeraraghavalu of the University of Chicago; Rudolph Tanzi, Can Zhang and Sean Miller of Massachusetts General Hospital; Jasmin K. Hefendehl and Mathias Jucker of the University of Tübingen; Tharinda W. Rajapaksha and Robert Vassar of Northwestern University Feinberg School of Medicine; and Jason Ulrich and David M. Holtzman from the Washington University School of Medicine.


Story Source:

The above story is based on materials provided by University of Chicago Medical Center. Note: Materials may be edited for content and length.


Journal Reference:

  1. K. Veeraraghavalu, C. Zhang, S. Miller, J. K. Hefendehl, T. W. Rajapaksha, J. Ulrich, M. Jucker, D. M. Holtzman, R. E. Tanzi, R. Vassar, S. S. Sisodia. Comment on "ApoE-Directed Therapeutics Rapidly Clear  -Amyloid and Reverse Deficits in AD Mouse Models". Science, 2013; 340 (6135): 924 DOI: 10.1126/science.1235505

Cite This Page:

University of Chicago Medical Center. "Multiple research teams unable to confirm high-profile Alzheimer's study." ScienceDaily. ScienceDaily, 23 May 2013. <www.sciencedaily.com/releases/2013/05/130523143004.htm>.
University of Chicago Medical Center. (2013, May 23). Multiple research teams unable to confirm high-profile Alzheimer's study. ScienceDaily. Retrieved October 26, 2014 from www.sciencedaily.com/releases/2013/05/130523143004.htm
University of Chicago Medical Center. "Multiple research teams unable to confirm high-profile Alzheimer's study." ScienceDaily. www.sciencedaily.com/releases/2013/05/130523143004.htm (accessed October 26, 2014).

Share This



More Health & Medicine News

Sunday, October 26, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Texas Nurse Nina Pham Cured of Ebola

Texas Nurse Nina Pham Cured of Ebola

AFP (Oct. 25, 2014) — An American nurse who contracted Ebola while caring for a Liberian patient in Texas has been declared free of the virus and will leave the hospital. Duration: 01:01 Video provided by AFP
Powered by NewsLook.com
Toxin-Packed Stem Cells Used To Kill Cancer

Toxin-Packed Stem Cells Used To Kill Cancer

Newsy (Oct. 25, 2014) — A Harvard University Research Team created genetically engineered stem cells that are able to kill cancer cells, while leaving other cells unharmed. Video provided by Newsy
Powered by NewsLook.com
IKEA Desk Converts From Standing to Sitting With One Button

IKEA Desk Converts From Standing to Sitting With One Button

Buzz60 (Oct. 24, 2014) — IKEA is out with a new convertible desk that can convert from a sitting desk to a standing one with just the push of a button. Jen Markham explains. Video provided by Buzz60
Powered by NewsLook.com
Ebola Protective Suits Being Made in China

Ebola Protective Suits Being Made in China

AFP (Oct. 24, 2014) — A factory in China is busy making Ebola protective suits for healthcare workers and others fighting the spread of the virus. Duration: 00:38 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins