[net-gold] Worth watching: ApoE-Directed Therapeutics Rapidly Clear Amyloid and Reverse Deficits in AD Mouse Models
- From: "David P. Dillard" <jwne@xxxxxxxxxx>
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- Date: Thu, 16 Feb 2012 17:56:51 -0500 (EST)
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Date: Wed, 15 Feb 2012 08:16:24 -0500
From: Dwight Hines <dwight.hines@xxxxxxxxx>
Reply-To: Net-Gold@xxxxxxxxxxxxxxx
To: Net-Gold@xxxxxxxxxxxxxxx
Subject: [Net-Gold] Worth watching: ApoE-Directed Therapeutics Rapidly Clear
Amyloid and Reverse Deficits in AD Mouse Models
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Worth watching: ApoE-Directed Therapeutics
Rapidly Clear Amyloid and Reverse Deficits
in AD Mouse Models
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This research is worth watching.
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Dwight Hines
Alzheimer's hope from cancer drug -
Health News -
NHS Choices
2/15/12 8:01 AM
Cancer drug eases Alzheimer's in mice
Behind the Headlines
.
Friday February 10 2012
.
Could cancer drug give hope to
Alzheimer's disease patients?
.
.
A skin cancer drug can improve
Alzheimer's-like symptoms in mice
engineered
to mimic the condition, it has been
widely reported.
.
Many national newspapers have covered
the news, which is based on animal
tests involving the drug bexarotene
(brand name Targretin), which is
currently only used to treat a rare
form of skin cancer. This drug was
given to mice that had been genetically
engineered to develop a condition
similar to Alzheimers, and in a short
space of time the mice showed
lowered brain levels of a key protein
called beta-amyloid. Beta-amyloid is
the substance that forms the protein
plaques in the brain that are
characteristic of Alzheimers.
The researchers also observed
post-treatment improvements in the
brain function of the mice for example,
they were better able to build nests
and remember the way through a maze.
.
Although this research is in animals
and there is limited direct
application to humans at the current
time, these early findings do show
some potential for further research.
Notably, the drug had a rapid effect
on amyloid plaques that are
characteristic of Alzheimers, and the
fact that the drug is currently licensed
means it will have undergone safety
regulations for its current use.
That said, there are no guarantees it
will prove as safe or effective in people
with Alzheimers.
.
At the current time no tests have
been carried out in humans with
Alzheimers, only an animal model of
the disease. The research will
undoubtedly be of interest to
researchers, doctors, and patients
and their families, but it is far
too early to suggest that this could
be a cure for Alzheimers.
.
Where did the story come from?
.
The study was carried out by
researchers from Case Western Reserve
University School of Medicine,
Cleveland, and other institutions
in the US. The study was supported by
a number of research funding foundations,
including the Blanchette Hooker
Rockefeller Fund, Thome Foundation, and
the Roby and Taft Funds for Alzheimers.
.
The study was published in the
peer-reviewed journal Sciencexpress.
.
BBC News gives accurate coverage of
this study. The Sun, Daily Mail and The
Daily Telegraph featured slightly
optimistic headlines, but their articles
generally do make it clear that this
was a study in mice and give good
accounts of the research.
.
What kind of research was this?
.
This was animal research aiming to
investigate the effects of a drug called
bexarotene on a mouse model of
Alzheimers disease.
.
Bexarotene activates a receptor on
the surface of cells that is known to be
involved in triggering the production
of a protein called apolipoprotein (ApoE).
The ApoE protein is involved
in the breakdown of soluble
beta-amyloid, a protein that builds
up to form the characteristic insoluble
plaques seen in the brains of people
with Alzheimers.
.
All humans carry a gene containing
the code for producing the ApoE protein,
but some people carry a particular
variant of the ApoE gene known as the
ApoE e4 allele. People carrying this
variant are known to be at increased
risk of developing Alzheimers disease,
and carrying this variant seems to
be associated with the build-up of
beta-amyloid plaques in the brain.
The researchers were interested whether
a drug that increases production of
ApoE could potentially have an effect
on the build-up of beta-amyloid in
the brain. To explore this possibility
they decided to test the drug in
mice with Alzheimers-like symptoms,
looking at whether it could reduce
their their beta-amyloid levels and
improve their cognitive performance.
.
What did the research involve?
.
The researchers used various different
genetically engineered mouse models
of Alzheimer’s in their experiments.
The researchers carried out a number
of tests to
.
http://www.nhs.uk/news/2012/02February/
pages/alzheimers-hope-cancer-drug.aspxPage
.
1 of 3
Alzheimer's hope from cancer drug -
Health News - NHS Choices 2/15/12 8:01
AM
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assess the effects of bexarotene on
soluble beta-amyloid in the fluid
surrounding the brain, insoluble
beta-amyloid plaques in the brain, and
cognitive performance of these mice.
.
The mice were administered oral
bexarotene for three, seven, nine, 14, 20
or 90 days. These mice were compared
with similar mice that did not receive
bexarotene. The researchers looked at
mice of three different ages – two
months, six months and 11 months in
order to look at the effects of the
drug when given to mice at different
stages of their Alzheimers-like
condition: the older mice having more
beta-amyloid protein build-up.
.
The mice in models of Alzheimers
display impairments in their performance
in several tasks: navigating a water
maze (an indicator of cognition); nest
construction (an indicator of social
behaviour); fear response to placement
in a shock chamber; and sense of smell.
In a sample of mice the researchers
tested performance in these four areas
after administering the drug.
.
After the treatment periods the mices
brains were examined to look for any
changes.
.
What were the basic results?
.
The researchers found that
administering a single dose of
bexarotene gave a rapid reduction
in levels of soluble beta-amyloid
in the fluid surrounding
the mices brains. There was a 25%
reduction within 24 hours and this
reduction was retained for over 70
hours. Up to 84 hours after treatment
there was a return to pre- treatment
levels of soluble beta-amyloid.
.
In six-month-old mice treated with
bexarotene, insoluble beta-amyloid
levels in the brain were reduced by
40% after 72 hours. When bexarotene was
given to mice for longer periods of
time they found a sustained reduction
in beta-amyloid throughout the
treatment period. They found comparable
effects of the drug when testing in
older, 11-month-old mice with greater
beta-amyloid build-up.
.
The drug also improved the cognitive,
social and sensory deficits of the
mice:
.
both six-month- and 11-month-old
mice treated for seven days showed
improvements in fear conditioning;
the six-month-old mice also showed
improvements in fear conditioning
with 90 days of treatment
performance in the water maze
improved after 20- and 90-day treatment
periods nest construction behaviour was
restored after 72 hours of treatment
.
ability to sense odours was restored
by three days of treatment
.
How did the researchers interpret
the results?
.
The researchers conclude that activation
of the receptor involved (the
retinoid X receptor) through use of
bexarotene helps to clear beta-amyloid
build-up in mouse models of Alzheimers
and gives a rapid reversal of the
associated cognitive and neurological
deficits.
.
Conclusion
.
This animal research has demonstrated
that bexarotene can have a positive
effect in clearing the build-up of the
characteristic beta-amyloid protein
plaques and improving cognitive
impairments in mouse models of Alzheimers.
.
Bexarotene (brand name Targretin)
is an anti-cancer drug that is currently
licensed specifically for the treatment
of a rare type of skin cancer
called advanced cutaneous T-cell lymphoma.
.
Although this research is in animals,
and therefore has a limited direct
application to humans at present,
these early findings do present some
genuine potential that needs further
research. There is bound to be great
interest in the finding that the drug
seemed to have an early effect on the
amyloid plaques characteristic of
Alzheimers, particularly as the study
involved a drug that is already
licensed for use in a specific, rare
type of cancer (advanced cutaneous
T cell lymphoma). Given its existing
use, there may be the possibility of
earlier testing in humans than there
would be if this were a completely new
chemical in development, which would
have completely unknown health and
safety effects. Nevertheless, this
drug has not yet been tested in humans
with Alzheimers, and results from such
studies will be needed before we
know for certain whether it is also helpful in humans.
.
Better treatments for Alzheimers in
humans are needed, and research such
as this is is an important early step
towards achieving this goal. While it
is far too early to say whether this
drug could be a cure for Alzheimers,
at least in the context of this early
research the drug has marked itself
out as a clear candidate for further
exploration.
.
Links to the headlines
.
Alzheimer's brain plaques 'rapidly
cleared' in mice. BBC News, February 10
2012
.
Skin cancer drug 'reverses Alzheimer's'.
The Daily Telegraph, February 10
2012
.
Skin cancer drug 'clears Alzheimer's
protein from the brain'. Daily Mail,
February 10 2012
.
Does skin cancer drug offer Alzheimer's hope?
Channel 4 News, February 10 2012
.
.
Cramer PE, Cirrito JR, Wesson DW, et al.
ApoE-Directed Therapeutics Rapidly
Clear β-Amyloid and Reverse Deficits
in AD Mouse Models Science.
Published
.
http://www.nhs.uk/news/2012/02February/
pages/alzheimers-hope-cancer-drug.aspxPage
.
2 of 3
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Alzheimer's hope from cancer drug -
Health News -
NHS Choices
2/15/12
8:01 AM
online February 9 2012
Analysis by
Edited by NHS Choices
http://www.nhs.uk/news/2012/02February/
pages/alzheimers-hope-cancer-drug.aspxPage
.
3 of 3
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