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.
A
POSSIBLE CURE FOR DOWN’S SYNDROME?
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.
SMOKING
& COGNITIVE
DECLINE
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.
CALCIUM
& VITAMIN D &
BREAST CANCER RISK
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.
