Betreff: RE: email regarding gene and melatonin..ALZ Org Scientist response... |
Von: Maria Carrillo |
Datum: Wed, 6 Jun 2007 08:25:58 -0500 |
|
CC: "Patricia Pinkowski" |
Dear Ms.
Mueller:
Thank you for sharing the information below. The reality of the
situation is
that unless many clinicians acknowledge the beneficial effects of
melatonin, or
a pharmaceutical company recognizes these benefits, a large clinical
trial,
which our current standard of testing treatments, will not be launched.
You
would be better served to launch your campaign with clinicians in
biotech or
pharma. I suspect most pharmas already have melatonin modulating
agents, and
may already be testing them. As you know, the trajectory for
studying an agent
in clinical trials is 12-15 years.
Best regards,
Maria
Carrillo
______________________________________
Maria
C.Carrillo, Ph.D.
Director,
Medical & Scientific Relations
Alzheimer's
Association, National Office
225
N. Michigan Ave., Suite 1700
Chicago,
IL 60601-7633
ph.312.335.5722
fx.866.741.3716
Asst:
Dee Moragne
312.335.5705
From:
Sent: Tuesday, June 05,
2007 11:28
PM
To: Maria Carrillo
Cc: Patricia Pinkowski;
Jennifer
Zeitzer
Subject: Re: email
regarding gene
and melatonin
Dear Dr.
Carillo: Thank you
for your prompt response.
While I
agree that additional research
regarding the beneficial effects of melatonin may be important, I
suspect you
may not have looked at my email appeal to Dr. Marilyn Albert which can
be
accessed by clicking on:
My appeal
specifically addresses
"prudent avoidance prevention measures."
To further
support the importance of my
appeal for the immediate release of "precautionary recommendations"
to the public, I have copied below a new study linking autism spectrum
disorders and melatonin (Mol Pyschiatry, 2007 May 15; [Epub ahead of
print],
Goubran et al, Human Genetics and Cognitive Functions, Institut
Pasteur, Paris,
France regarding the ASMT gene::
*
*
*
Mol Psychiatry. 2007 May 15; [Epub ahead of
print]
Melke J, Goubran Botros H, Chaste P, Betancur C, Nygren G, Anckarsäter H, Rastam M, Ståhlberg O, Gillberg IC, Delorme R, Chabane N, Mouren-Simeoni MC, Fauchereau F, Durand CM, Chevalier F, Drouot X, Collet C, Launay JM, Leboyer M, Gillberg C, Bourgeron T.
1Human
Genetics and Cognitive Functions, Institut Pasteur,
Melatonin
is produced in
the dark by the pineal gland and is a key regulator of circadian and
seasonal
rhythms. A low melatonin level has been reported in individuals with
autism
spectrum disorders (ASD), but the underlying cause of this deficit was
unknown.
The ASMT gene, encoding the last enzyme of melatonin synthesis, is
located on
the pseudo-autosomal region 1 of the sex chromosomes, deleted in
several
individuals with ASD. In this study, we sequenced all ASMT exons and
promoters
in individuals with ASD (n=250) and compared the allelic frequencies
with
controls (n=255). Non-conservative variations of ASMT were identified,
including a splicing mutation present in two families with ASD, but not
in
controls. Two polymorphisms located in the promoter (rs4446909 and
rs5989681)
were more frequent in ASD compared to controls (P=0.0006) and were
associated
with a dramatic decrease in ASMT transcripts in blood cell lines (P=2 x
10(-10)). Biochemical analyses performed on blood platelets and/or
cultured
cells revealed a highly significant decrease in ASMT activity (P=2 x
10(-12))
and melatonin level (P=3 x 10(-11)) in individuals with ASD. These
results
indicate that a low melatonin level, caused by a primary deficit in
ASMT
activity, is a risk factor for ASD. They also support ASMT
as a susceptibility gene for ASD and highlight the crucial role of
melatonin in
human cognition and behavior.
Molecular Psychiatry advance online publication, 15
May 2007; doi:10.1038/sj.mp.4002016.
PMID:
17505466 [PubMed -
as supplied by publisher]
*
*
*
The
following study published in Behavioral
Brain Function 2006; 2: 15...."Melatonin in Alzheimers' disease and
other
neurodegenerative disorders," provides 343 references to support
information regarding aging and adverse effects of low levels of
melatonin
regarding free radical damage and also explains in detail, evidence
supporting
protective benefits as result of increased melatonin
levels. This
study comprises 37 pages of valuable explanations.
*
* *
Behav Brain
Funct. 2006; 2: 15.
Published
online 2006 May 4. doi: 10.1186/1744-9081-2-15.
Copyright
©
2006 Srinivasan et al; licensee BioMed Central Ltd.
Melatonin
in Alzheimer's
disease and other neurodegenerative disorders
V
Srinivasan,1 SR
Pandi-Perumal,2 DP Cardinali,3 B Poeggeler,4
and R Hardeland4
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1483829
THE LAST
TWO PARAGRAPHS OF CONCLUSIONS
ARE COPIED
BELOW:
"......... the balance seems to be
largely in favor
of melatonin in the case of AD.
Apart from the positive effects in experimental systems concerning
antagonism
of oxidative stress, fibrillogenesis and tangle formation, the
sleep-promoting
effects – even if not demonstrable in all individuals – and the suppression
of sundowning are important results justifying the use melatonin.
Mild
cognitive improvements should also be welcome. The problem in AD
remains to
which extent melatonin may be effective in retarding disease
progression. One
should not expect too much in an advanced state. Nevertheless, the
preventive
potential of melatonin deserves attention and continued investigation.
Even
from a cautious and realistic, perhaps even sceptical point of view,
the
findings obtained to date should be taken as a good reason for planning
further
multicenter trials, in which, however, the collectives of patients have
to be
large enough for distinguishing between different stages of disease
progression. Whether or not melatonin may have a preventive potential
might
become clear in subpopulations of high-risk individuals, e.g. those
with
pertinent familial history or carrying unfavorable apolipoprotein
variants.
With regard
to prevention, melatonin should also
be seen in the general context of aging. In the
past, this has been a matter of controversy, but mainly for
methodological
reasons. Recent studies show that age-dependent patterns of gene expression
can be
reverted to a more juvenile state in the mouse CNS [343]. Life
extension with melatonin is possible in model animals, but melatonin's value is
not only a
matter of life-span, but also of health during aging,
and pertinent observations have, in fact, been made in mammals [262]........."
*
*
*
Information
re the ASMT Gene is accessible by
clicking on:
*
*
*
Information
re the ASMT Gene (abnormal melatonin
synthesis) indicates melatonin plays "a crucial role in human
cognition and behavior. Even tho these facts "focus" on
autism-like disorders, the information applies to all neurodegenerative
diseases including Alzheimers.
I have
provided information regarding
"prudent avoidance measures" that were previously recommended re
electrical items close to beds proving that the American Cancer Society
as well
as the electrical industries' own communications' experts know that
EMF/EMR
close, chronic, prolonged exposures at night may be potentially harmful.
Low level
EMF/EMR (electromagnetic
fields/electromagnetic radiation) is considered "toxic" and has been
designated as a Class 2B carcinogen by the National
Institute of
Environmental Health Sciences -- possible cancer promoter in the same
class as
benzene which is known to be linked to Leukemia.
Many, if
not most of the 343 studies re
melatonin (see Behav Brain Funct study above) involve various
observations and
results re cell signaling, electron transport and other aspects of,
or
simulating EMF/EMR exposures.
Reducing
electrical exposures re my two
grandsons as well as my husband (see: http://freepage.twoday.net/stories/3038870/
) resulted in significant improvement in all
cases. The same results occurred in two of my guinea pigs who
survived
exposure to electric meters.
It is known
that light, which is part of the
electromagnetic radiation spectrum, as well as UV (sunlight) reduces
melatonin
levels. Studies have also confirmed that melatonin is protective
in those
instances as well as many other situations including apparent increases
in
natural production of melatonin in my two grandsons after moving their
beds
away from electric meters, as well as probable increase in my husband's
own
production of melatonin (even tho at an age when natural melatonion
production
is reduced) or else supplementation with nightly melatonin is/was
responsible
for his improvement in three parts of his Execuive Function (neuropsych
tests).
While
reasons can always be fround to conduct
more research and we do need more information as to potential
preventative
effects of melatonin, it is my plea that the Alzheimers' organization
do what
our politicians are not willing to do. We must have
"prudent
avoidance recommendations" reinstituted while awaiting further studies
that will provide insight into whether or not Alzehimers, autism and
other
neurodegenerative disorders can in fact be prevented or the adverse
effects be
significantly reduced.
The
evidence is "overwhelming" that
increased levels of melatonin are more likely than not, "very
beneficial" in regard to reducing the severity of behavioral problems
and
cognitive dysfunction in autism, Alzehiemrs and other neurodegenerative
problems.
I ask,
"what harm will come to those who
move electrical and telephone items away from close proximity to beds
while
awaiting further studies? Surely we can not afford to
"carry
on as usual" and let the tragedies continue to mount
up.
Will the Alzheimers' Association help re this vital cause? Can
you
contact Senator Hillary Clinton, another member of the Alzheimers' Task
Force
and also a senatorial member of a committee on aging to help arrange
for me to
testify before Congress? I would also appreciate learning
why Dr.
Marilyn Albert, a new member of the Alzheimers' Advisory Board Task
Force has
not yet responded to my appeal?
The future
of our
Joanne C.
Mueller
Guinea Pigs R Us
731 -
Phone: 763-755-6114
Email: jcmpelican@aol.com
(6-5-07)
All truth
goes through three stages: first it is
ridiculed:
then it is violently opposed: finally it is accepted as self
evident. -
Schopenhauer
"No
substance is a poison by itself. It is
the dose that makes a substance a poison..." Paracelsus
(1493-1541)
.