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" , "Jennifer Zeitzer"

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




Asst: Dee Moragne


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::


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 Mol Psychiatry. 2007 May 15; [Epub ahead of print]Click here to read Links

Abnormal melatonin synthesis in autism spectrum disorders.

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, Paris, France.

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/

PMID: 17505466 [PubMed - as supplied by publisher]

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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.   

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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 Hardelandcorresponding author4

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]........."

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Information re the ASMT Gene is accessible by clicking on:


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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:    )     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 U.S. healthcare system is "literally in your hands....."     Take care  -  Joanne

Joanne C. Mueller
Guinea Pigs R Us
731 - 123rd Avenue N.W.
Minneapolis, Minnesota  55448-2127 USA
Phone:   763-755-6114
Email:  (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)