Health Report:

A Possible Cure for Down's Syndrome?

Smoking & Cognitive Decline

Calcium & Vitamin D & Breast Cancer Risk

"A critical weekly review of important new research findings for health-conscious readers..."

By, Robert A. Wascher, MD, FACS

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Last Updated:  11/30/2008

The information in this column is intended for informational purposes only, and does not constitute medical advice or recommendations by the author.  Please consult with your physician before making any lifestyle or medication changes, or if you have any other concerns regarding your health.


Down’s syndrome, or trisomy 21, is the most common of the trisomy disorders.  As with other trisomy disorders, an extra copy of a chromosome is present, resulting in three copies instead of the normal two copies (in the case of trisomy 21, an extra chromosome 21 is present).  Trisomy 21 occurs in approximately 1 of every 800 births in the United States, and becomes more common with advancing maternal age and, to a lesser extent, with advancing paternal age.  A constellation of clinical abnormalities is associated with this disorder, including varying degrees of decreased cognitive development, structural heart abnormalities, recurrent respiratory infections, suppressed immune function, epilepsy, Alzheimer’s disease, thyroid dysfunction, intestinal obstructions, and leukemia; as well as the characteristic physical abnormalities that occur with this syndrome.  The lifespan of children born with Down’s syndrome is generally much shorter than that of the general population, due to this constellation of associated abnormalities.  Recently, during the presidential elections in the United States, trisomy 21 received an unusual amount of publicity as a result of then Republican vice-presidential candidate Sarah Palin’s youngest child, Trig, who was born with Down’s syndrome.

Earlier this year, I summarized the exciting results of an experimental treatment for Down’s syndrome in laboratory mice with the mouse-equivalent of trisomy 21 (http://doctorwascher.com/Archives/2-10-08).  In this experiment, treatment with two “neuroprotective” proteins improved the ability of mice with Down’s syndrome to learn how to navigate a water maze.  Amazingly, this experimental treatment appeared to restore the learning capabilities of these mice with Down’s syndrome such that they were able master a water maze just as quickly as normal laboratory mice.  Now, a newly published laboratory research study, just published in the journal Obstetrics & Gynecology, has shown that these two neuroprotective proteins (NAPVSIPQ and SALLRSIPA), when given to pregnant mice with the mouse-equivalent of trisomy 21, were able to significantly reduce the extent of cognitive delays in the trisomy offspring of these pregnant mice.  This study builds upon previous groundbreaking trisomy 21 research at the National Institutes of Health with these same neuroprotective proteins.  (These proteins have also been shown to prevent the severe developmental delays associated with fetal-alcohol syndrome in laboratory mice, as well.)

In this study, pregnant mice with the mouse-equivalent of trisomy 21 were randomly assigned to receive either “NAPVSIPQ plus SALLRSIPA” or a placebo treatment.  Interestingly, the research personnel who subsequently tested the offspring of these pregnant mice were “blinded” as to which of the baby mice had inherited the extra gene (trisomy) from their trisomy mothers, and which mice had received NAPVSIPQ and SALLRSIPA during their mothers’ pregnancies, something that is usually done only in clinical research trials involving human volunteers.

The untreated baby mice with trisomy experienced significant delays in the majority of the evaluated sensory and motor developmental milestones, as expected.  However, the trisomy offspring of the pregnant mice that had been treated with NAPVSIPQ and SALLRSIPA during pregnancy achieved normal developmental milestones in 3 out of 4 motor milestones, and in 1 out of 4 sensory milestones.  Another fascinating finding in this study was that genetically normal baby mice, without trisomy, that were treated with NAPVSIPQ and SALLRSIPA actually reached their normal developmental milestones earlier than their genetically normal siblings who were not treated with NAPVSIPQ and SALLRSIPA during their mother’s pregnancies!  

When the researchers evaluated the concentrations of two brain proteins that are known to be significantly decreased in patients with trisomy 21 (activity-dependent neurotrophic factor and glial fibrillary acidic protein), they found normal levels of these two critical proteins in the brains of trisomy mice that had been exposed to NAPVSIPQ and SALLRSIPA during their mothers’ pregnancies, while the trisomy mice that had been exposed only to a placebo during their mothers’ pregnancies had, as expected, decreased brain levels of these proteins.

I find the results of this study to be astonishing, and on several levels.  Many experts on Down’s syndrome have believed that some sort of gene therapy holds the key to treating Down’s syndrome.  But there have been many hiccups, so far, in developing a safe and reliable method of inserting individual genes into human hosts in a way that will also efficiently supply important missing proteins.  On another level, this research study has also shown that, at least in mice, treating pregnant mothers with trisomy fetuses can substantially correct both the biochemical defects in the brain associated with Down’s syndrome and the characteristic developmental delays of this disorder.  And, on yet another level, the treatment of pregnant mice with NAPVSIPQ and SALLRSIPA also appeared to accelerate the cognitive development of otherwise normal mice!  
While it is too soon to assume that NAPVSIPQ and SALLRSIPA will have these same rather miraculous effects in human mothers and their babies with Down’s syndrome, the possibility that the cognitive abnormalities associated with this often profoundly disabling genetic disorder might, essentially, be reversible following treatment with NAPVSIPQ and SALLRSIPA is striking, to say the least.  Clearly, it is time to begin testing these proteins in humans in carefully constructed early phase clinical trials.    



By now, everyone knows that smoking is associated with an increased risk of lung cancer (and other cancers), as well as chronic lung diseases, cardiovascular diseases, and impotence.  A new clinical research study from the Netherlands also suggests that chronic smoking is associated with a significant decrease in higher level brain function during middle age. This study has just been published in the American Journal of Public Health.

In this study, nearly 2,000 men and women between the ages of 43 and 70 years underwent cognitive function testing, including memory function, at the time that they entered into the study, and again 5 years later.  The results of these cognitive tests, in smokers and non-smokers, were then compared and analyzed.  

Not surprisingly, the news is rather bad for the smokers who participated in this research trial.  First of all, even at the point when they first entered into the study, the smokers’ cognitive functioning level was already significantly lower than that of the age-matched non-smokers.  Five years later, when all of the study volunteers were reassessed, things looked even worse for the smokers, including a 2-fold decline in memory function, a 2.4-fold decline in cognitive flexibility, and a 1.7-fold decline in global cognitive function, when compared with the non-smokers.  Moreover, these declines in higher level brain function became more severe as the number of cigarettes smoked, and the duration of smoking, increased.  

As if there wasn’t already an overwhelming number of reasons to quit smoking (or, better yet, to never begin smoking in the first place), you can now add accelerated cognitive decline to the list.



There have been multiple public health studies published so far that have suggested a link between Vitamin D and calcium supplements on the one hand, and a reduction in breast cancer risk on the other hand.  Most of these studies have relied upon dietary surveys to assess Vitamin D and calcium intake, and the duration of follow-up in many of these studies has been relatively brief.

Now, as is becoming increasingly common as large prospective human trials looking at the effects of dietary supplements begin to report their results, a new prospective placebo-controlled clinical trial is casting doubt upon Vitamin D and calcium supplements as potential breast cancer prevention aids.  This new study has just been published in the Journal of the National Cancer Institute.  

The huge Women’s Health Initiative study enrolled more than 36,000 postmenopausal women into a clinical trial that randomized the women to receive either a combination of Vitamin D and calcium supplements or placebo (sugar) pills. Among this very large group of women volunteers, 1,067 women from each group underwent testing of the Vitamin D levels in their blood.  All of these 2,134 patient volunteers were then followed for an average of 7 years, and the subsequent incidence of breast cancer among these women was then analyzed. 

In this study, the first ever randomized prospective clinical trial to look at the role of Vitamin D and calcium supplements as potential breast cancer prevention aids, no difference in the incidence of breast cancer was identified, after an average of 7 years, between each group of 1,067 women.  Thus, there was no evidence of a protective effect against breast cancer observed among the women who had been taking Vitamin D and calcium supplements when compared to the women who had taken the placebo pills.  Likewise, higher Vitamin D levels in the blood did not appear to provide any protection against breast cancer either.  

The results of this very high quality prospective clinical trial are very disappointing, especially since other less powerful studies have appeared to show a breast cancer prevention effect with Vitamin D and calcium supplements, and with higher levels of Vitamin D in the blood.   However, as the editors of the Journal of the National Cancer Institute have pointed out, there are two important limitations of this study.  First, some study participants were allowed to take Vitamin D and calcium supplements on their own, outside of the randomization scheme of the study.  Secondly, the average duration of patient follow-up in this study (7 years) may not yet be adequate to reveal any modest breast cancer prevention effects that might be associated with long-term Vitamin D and calcium supplementation.  It may, therefore, require an additional period of observation of the patient volunteers in this study before the final word is in regarding Vitamin D and calcium supplements and their role, if any, in breast cancer prevention.  Meanwhile, I recommend that women follow the current guidelines for dietary calcium and Vitamin D intake, as these supplements are essential to prevent osteoporosis later in life.

Disclaimer:  As always, my advice to readers is to seek the advice of your physician

before making any significant changes in medications, diet, or level of physical activity.

Dr. Wascher is an oncologic surgeon, professor of surgery, a widely published author, and the Director of

 the Division of Surgical Oncology at Newark Beth Israel Medical Center:


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Copyright 2008.  Robert A. Wascher, MD, FACS.  

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