Saturday, February 18, 2012

Cancer Drug Reverses Symptoms Of Alzheimer's In Mice


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A drug approved for the treatment of cancer appears to quickly reverse the symptoms of Alzheimer's in mice, according to a new study from the US published in the journal Science on Thursday.

The Food and Drug Administration (FDA) approved bexarotene as a treatment for cutaneous T cell lymphoma, a type of skin cancer, in 2000. Now a team of neuroscientists has shown that when they gave the drug to mice with Alzheimer's disease, it quickly reversed the pathological, cognitive and memory deficits that accompanies it.

About 5.4 million Americans have Alzheimer's disease, the most common form of dementia. While the cause of the disease is not well understood, studies have shown it is linked to an inability to clear away beta-amyloid plaques that accumulate around brain cells.

The study was conducted in the lab of senior author Dr Gary Landreth, professor of neurosciences at Case Western Reserve University School of Medicine in Cleveland, Ohio.

From previous work, Landreth had already established that the protein Apolipoprotein E (ApoE), the main cholesterol transporter in the brain, also helps to clear away amyloid beta.

So, he and his colleagues decided to see what effect bexarotene might have on this process, since it was already known that one of the effects of the drug is that it stimulates a group of receptors that help control production of ApoE, the retinoid X receptors (RXR).

They were astonished at the results.

Within six hours of administering bexarotene, levels of soluble amyloid levels fell by 25%. And they were even more impressed when they saw the effect lasted for three days, at which point there was more than 50% reduction in amyloid beta plaques. Eventually, the reduction was more than 75%.

And finally, the change in amyloid levels was accompanied by rapid improvement in a range of observable behaviors in the three different types of mouse model of Alzheimer's that they used:

"... bexarotene stimulated the rapid reversal of cognitive, social, and olfactory deficits and improved neural circuit function," write the authors.

One improvement they noticed was in the mice's nesting behavior. Before receiving bexarotene, the Alzheimer's-diseased mice did not start to make a space for a nest when they encountered tissue paper. But just 3 days after treatment, they started to use the paper to make nests.

Landreth and colleagues conclude that activating the RXR receptors with bexarotene "stimulates physiological [amyloid beta] clearance mechanisms, resulting in the very rapid reversal of a broad range of [amyloid beta]-induced deficits".

Speculating on their findings, Landreth and colleagues suggest that bexarotene reprogrammed the brain's immune cells (the phagocytes, white blood cells that ingest unwanted material) to eat away the amyloid deposits. They believe their observations show that the drug stimulates removal of both soluble and deposited amyloid beta.

Human beings have three forms of gene that code for the ApoE protein: ApoE2, ApoE3, and ApoE4. People with the ApoE4 variant have a much greater risk for developing Alzheimer's disease.

In a statement, Landreth described the study, which started as a "far-fetched idea", as "particularly exciting and rewarding" because they have uncovered new information and the potential promise of a new treatment for Alzheimer's disease. But he added a word of caution:

"We need to be clear; the drug works quite well in mouse models of the disease. Our next objective is to ascertain if it acts similarly in humans. We are at an early stage in translating this basic science discovery into a treatment."

In the meantime, he and his colleagues hope that, since bexarotene has a good safety and side-effect profile, these will help speed the transition to clinical trials.

Funds from the Blanchette Hooker Rockefeller Foundation, the Thome Foundation, and the National Institutes of Health helped pay for the study.

Written by Catharine Paddock PhD
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today

Additional References Citations Visit our alzheimer's / dementia section for the latest news on this subject. "ApoE-Directed Therapeutics Rapidly Clear [beta]-Amyloid and Reverse Deficits in AD Mouse Models"; Paige E. Cramer, John R. Cirrito, Daniel W. Wesson, C. Y. Daniel Lee, J. Colleen Karlo, Adriana E. Zinn, Brad T. Casali, Jessica L. Restivo, Whitney D. Goebel, Michael J. James, Kurt R. Brunden, Donald A. Wilson, and Gary E. Landreth; Science, Published online 9 February 2012; DOI:10.1126/science.1217697; Link to Abstract.
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Visitor Opinions In Chronological Order (3)relative of Alzheimer's suffererposted by Robert Charles on 11 Feb 2012 at 11:13 am

Thank God for the dedicated staff and their findings. I pray that this means true hope for sufferers. What would the world do without America and her Scientists.

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INFLIXIMAB HAS DONE IT TWO YEARS AGO!posted by JUN XU on 11 Feb 2012 at 6:25 pm

OUR TEAM DISCOVERED INFLIXIMAB DECREASED AMYLOID RAPIDLY IN TRANSGENIC MICE BRAIN TWO YEARS AGO, WHICH PUBLISHED ON "BRAIN RESEARCH" JAN 2011.

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Why is the public clueless?posted by mary on 15 Feb 2012 at 12:31 pm

We see two drugs here within a two year period, that show so much promise for AD. Yet as a caregiver of a stage 6 Alzheimer's patient no attempt has been made to inform us of either one by a neurologist or MD.

There are patients and families out here that would jump at the chance to try either drug in the hope that it can improve their current condition.

Why is the health community not doing more to get these drugs out into the AD population, since the standard drugs used are not effective? These drugs were also adapted from approved drugs for other conditions , just as bexarotene now used for cancer treatment, is found to be effective for AD.

This is very frustrating to families and patients struggling with the care of and experience with, Alzheimers. Not to mention the enornous expense for drugs that give minimal help and the outside medical care that is required.

Is it no wonder that healthcare costs keep rising ......solutions are not being added into the equation. I am not niave to believe that this is the only problem with costs....... that is another long discussion, not meant for here.

IF THERE IS A DRUG OR PRODUCT OUT THERE THAT SHOWS SIGNIFICANT POSITIVE SAFE RESULTS FOR ANY DISEASE, THE PUBLIC SHOULD BE GIVEN THE INFORMATION QUICKLY AS WELL AS GIVEN THE OPPORTUNITY TO CHOOSE WHETHER OR NOT TO USE IT.

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Everyday Health Network
Alzheimer's / DementiaWhat is Dementia?The word dementia comes from the Latin de meaning "apart" and mens from the genitive mentis meaning "mind". Dementia is the progressive deterioration in cognitive function - the ability to process thought (intelligence). Read more...What Is Alzheimer's Disease?Alzheimer's disease is a progressive neurologic disease of the brain leading to the irreversible loss of neurons and the loss of intellectual abilities, including memory and reasoning. Read more...Most Popular Articles

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