by Bill Sardi: Online
Insignificance: Buried on Google Search Page 23
failure of an Alzheimer’s drug trial threatens to leave the world
with no effective remedies to head off an explosive increase in
the numbers of people affected by this disease. By the year 2040
there may be as
many as 80 million human zombies on the planet, adults who have
lost their memory, ability to communicate, make judgments and live
humanity is running out of time, that the lengthening lifespans
across the globe will surely increase the incidence of Alzheimer’s
dementia, drug companies have stepped up their research and development
programs in hopes of reaping huge financial rewards. But sadly their
efforts have fizzled.
Two major drug
trials were in the research and development pipeline but one
was just nixed off the list when the drug (bapineuzumab) was
withdrawn from further human study by its pharmaceutical sponsors.
That leaves another similar drug (solanezumab) as possibly
the last hope for millions of senior adults suffering from this
debilitating brain disease. Data will soon be announced on this
drug, but this author doesn’t give it much hope, as it is a monoclonal
antibody drug in the same class as the failed bapineuzumab.
researchers hold out hope for solanezumab saying it has a good
safety profile so far in Phase II studies among Alzheimer’s patients
and favorably alters cerebrospinal and blood plasma markers. But
altering markers is a long way from heading off this slowly progressive
diagnose it first
Even if a drug
is proven to be effective in heading off the progression of the
disease, modern medicine first has to agree upon an early pre-disease
marker (a blood test most likely) that can be quantified.
Wilson, writing from the Department of Pharmaceutics, Dayananda
Sagar College of Pharmacy, in Bangalore, India, says:
major problem with Alzheimer’s disease is its diagnosis. Even
though magnetic resonance imaging, positron emission tomography,
single positron emission computerized tomography, spinal fluid
biochemistry and other laboratory tests are helpful to identify
and study disease progression, a simple and effective diagnostic
test is required to identify the disease at an early stage of
disease progression. Lack of awareness results in low rates of
recognition of disease by family members and physicians… Reportedly,
the rates of such failure to recognize cases are 97% for mild
Alzheimer’s disease and 50% for moderate Alzheimer’s disease."
have recently identified
four blood markers (TNF (tumor necrosis factor), apolipoprotein
E, C-reactive protein and B-type natriuretic peptide) as possible
blood tests that could be employed to identify patients with the
earlier signs of the disease.
currently prescribes ineffective drugs
desperate pleas from families of loved ones affected by this brain
disease, physicians often pacify their patients and prescribe ineffective
drugs. While it is widely reported that "there are no medicines
on the market that slow the progression of the disease," the
pharmaceutical industry sells millions
of dollars of ineffective drugs for use among Alzheimer’s patients,
an enzyme (acetycholinesterase) inhibitor being the most commonly
if health reform is going to put a halt to these ineffectual drugs
and trigger a public upheaval that will likely end up parading Alzheimer’s
patients and their families before Congress in hearings to decide
if withholding these drugs represents rationing.)
drug journal has just announced the French Pharmaco-economic Committee
existing drugs (Aricept, Namenda, Exelon, Razadyne and Cognex) prescribed
for Alzheimer’s patients, saying "they are best avoided
and have no therapeutic advantage."
there is another drug
writing at Med
Page Today, says with children of Alzheimer’s disease patients
clamoring for a drug, in this case a drug that is already FDA approved
but for another condition entirely (cutaneous T-cell lymphoma),
puts physicians in an awkward position. The drug is bexarotene.
When bexarotene was used among laboratory mice genetically bred
to develop amyloid plaque in their brains. It astonishingly reduced
the plaques by 50% within 72 hours. While other drugs have been
successful in animal models of Alzheimer’s disease, they have failed
in human trials, including one of the recent drugs (bapineuzumab)
where a human trial was halted.
But while Gregory
Jicha MD, PhD, at the University of Kentucky at Lexington, says
bexarotene should not be prescribed until tested "with appropriate
safety oversight," he also says "the impetus to do something
is quite high." But the true safety profile of FDA approved
drugs is not even known till they are put into use in large groups.
Late safety data is what brought the recalls of drugs like Vioxx.
And bexarotene is already known to have a host of adverse effects
which includes liver damage, pancreatitis, hypothyroidism, leukopenia
(low white blood cell count) and elevated cholesterol. This sounds
like disease substitution, not disease prevention. But the question
arises, will physicians begin to prescribe bexarotene for off label
at the National Institutes of Health (NIH), writing in the New
England Journal of Medicine, have dropped the idea that any
promising small group study using bexarotene among patients with
early Alzheimer’s might prompt families of affected loved ones to
beg their doctors for this drug. Sudden overwhelming pleas to do
something by family members may be difficult for politicians to
deal with and they might exert pressure to prescribe. The NIH researchers
say "the early promise of bexarotene in a mouse model of Alzheimer’s
disease is exciting."
But why have
NIH researchers chosen bexarotene over many other promising molecules,
most of them being dietary supplements? Why not off-label use of
dietary supplements for Alzheimer’s disease. The pro-drug lobby
can’t say these natural remedies are unproven because neither are
the drugs. In fact, some have been disproven but millions of dollars
of these ineffective pills are still prescribed. There is at least
as much scientific evidence for dietary supplements as remedies
for Alzheimer’s disease as there is for bexarotene, so why aren’t
NIH researchers "excited" about them?
there may be as much evidence that an East Indian herb quells Alzheimer’s
disease as there is for bexarotene. A promising study with an East
Indian herb, ashwaganda, reversed
behavioral changes and brain plaque accumulation in the brains of
middle-aged and old mice that were bred to develop Alzheimer’s
There is reasonable
evidence to suggest supplemental
melatonin may be helpful for Alzheimer’s patients.
(vitamin B1), given in its more absorbable form (benfotiamine),
is said to exhibit "powerful effects" in improving mental
function of laboratory animals in a model of Alzheimer’s disease.
Researchers are practically begging the National Institutes of Health
to launch a study
of vitamin B1 for Alzheimer’s disease.
have already employed fairly high-dose antioxidants (vitamin E,
vitamin C, lipoic acid, coenzyme Q10) among subjects with mild to
moderate Alzheimer’s disease, but these appeared
to accelerate mental decline over a period of 16 weeks even
though a marker of oxidation declined in cerebrospinal fluid. Markers
of tau protein and beta amyloid did not decline with use of this
antioxidant cocktail. The relative high dosage of antioxidant used
in this study may be the problem here.
to the rescue?
If female mammals
have their estrogen-producing ovaries removed they develop problems
with thinking and memory. If
estrogen is replaced, learning and memory improves in animals.
use of estrogen has been shown to improve measures of attention,
orientation, mood and social interaction among women with Alzheimer’s
disease. But the Women’s Health Initiative study, published in 2002,
horrified menopausal women as they learned their hormone pills might
increase their risk for breast cancer, Alzheimer’s disease and stroke.
But upon careful re-examination, researchers report that the recommendation
to back away from estrogen replacement was based upon "findings
reported in press releases and interviews of the principal investigators
that were often distorted, oversimplified, or wrong." Why have
American women been unduly frightened away from estrogen replacement?
as a weak plant estrogen, shows promise as an alternative to estrogen
in the prevention and treatment of Alzheimer’s disease.
And who knows,
we shouldn’t be solely looking toward pills to remedy this disease.
beta amyloid brain plaque define the disease?
bapineuzumab and solanezumab are designed to halt the accumulation
of a cholesterol-like plaque called beta amyloid in the brain. But
the whole idea of inhibiting beta amyloid buildup in the brain is
being called into question. Ryan McBride, writing at FierceBiotech.com,
industry watchers have been left scratching their heads over the
utility of attacking beta amyloid." Matthew Herper, medical
writer for Forbes Magazine, says "skeptics
don’t believe the basic theory behind bapineuzumab, that plaques
of a chemical are a cause of Alzheimer’s, are true."
medicine should be studying are the cases of minimal brain plaque
that have been confirmed among a few centenarians. It is possible
to live 100+ years and not be senile. Documentation is found here
What is striking is that neither the number of surviving brain cells
(neurons) nor volume of amyloid brain plaque is
significantly related to the clinical dementia rating that geriatricians
use to measure severity of Alzheimer’s disease in these centenarians.
interest is the red wine molecule resveratrol, which does not inhibit
or block the production of beta amyloid like the failed monoclonal
antibody drugs that modern pharmacology has fabricated, but rather
to degrade beta amyloid and assist in its exit (efflux) from the
brain. One report
written over a decade ago said "neuronal cell death due
to oxidized brain lipids (fats) could be ameliorated by resveratrol,
a polyphenolic compound known for its antioxidant properties."
The toxic form of beta amyloid plaque that is described as a powerful
neuron killing machine is
inhibited by resveratrol.
A drug must
cross the blood–brain barrier to exhibit therapeutic activity.
The idea of
employing minified molecules within the range of 1 to 100 nanometers
(one billionth of a meter) has been facilitate passage of drugs
across the blood-brain barrier. Only
a few attempts have been made to deliver anti-Alzheimer’s drugs
into the brain using nanoparticles.
can absorb particles with a size less than 100 nanometers (billionth
of a meter) in one dimension. Brain cells are capable of delivering
drugs at the cellular and molecular level to treat brain diseases
natural molecules from botanical sources are naturally nano-sized
and do not require nano-sizing by man. Included in a list of naturally
nano-sized molecules that may have application for Alzheimer’s disease
are the following:
A very intriguing
natural molecule, founds in miniscule amounts in tea leaves and
apple peel known as 7,8-dihydroxyflavone has gained considerable
attention in the past two years for its ability to mimic something
called brain-derived neurotrophic factor (BDNF). So far, BDNF
has reversed experimentally-induced memory loss in the animal lab.
itself is not stable and can’t cross the blood-brain barrier,
a defense against toxins entering the brain, so it cannot be employed.
But 7,8-dihydroxyflavone can pass through the blood-brain barrier.
It is also known to produce
an anti-depressant effect.
A problem is
that 7,8-dihydroxyflavone is currently not available as a dietary
supplement ingredient and would likely have to be synthetically
(rez-vair-ah-troll), known as a red wine molecule, is widely available
and has been demonstrated
to promote the natural production of BDNF in a laboratory dish
and in lab
animals. As an aside, BDNF
also inhibits food consumption and may be a welcome mechanism
for controlling obesity. Obesity
is in fact linked to Alzheimer’s disease. Bariatric
(weight-loss) surgery for obesity has been demonstrated to produce
better cognition (thinking).
exercise has been shown to elevate the production of BDNF and
exercise has been found to be somewhat beneficial among Alzheimer’s
subjects. The link between BDNF
and exercise in Alzheimer’s disease has been intensely explored.
with resveratrol is that researchers falsely believe it is not bioavailable
and cannot traverse the blood-brain barrier. To penetrate
the blood-brain barrier molecules must be below about 500 Daltons
in molecular weight. Resveratrol has a molecular weight of 228
Daltons and should readily enter the brain. Other similar-sized
red wine molecules have been demonstrated to pass
through brain capillaries grown in a lab dish. More intriguingly,
dietary supplement has been demonstrated to resolve human cases
of retinal disease (wet macular degeneration) and thus pass through
the blood-ocular barrier, so these and other similar molecules must
be passing into the brain.
Dr Edward Tobinick says drugs do not have to pass through the blood-brain
barrier per se but send cellular signals via intermediary cells
(tancytes) that contact the cerebrospinal fluid. So Alzheimer’s
drugs need not work directly upon the contact points (synapses)
of adjoining brain cells (neurons). Dr. Tobinick says this challenges
the dogma that penetration of a drug through the blood-brain barrier
is necessary to produce rapid clinical effects
On an encouraging
note, a human
study of resveratrol will soon begin among patients with early-stage
Alzheimer’s disease. But researchers have decided to employ
what may be a toxic high-dose of resveratrol, under the false assumption
more is needed to get a little bit into the brain. These mega-doses
of resveratrol may doom the molecule forever. Measured low doses
of resveratrol activate a gene transcription factor known as Nrf2
which stimulates the natural activity of enzymatic antioxidants
glutathione, catalase, superoxide dismutase and heme oxygenase.
One would get the impression researchers are intentionally trying
to doom this promising natural molecule that has already
produced health benefits for humans in two trials. You can read
the whole worrisome story about the upcoming
resveratrol/Alzheimer’s study here.
him mail] is a frequent writer on health and political
topics. His health writings can be found at www.naturalhealthlibrarian.com.
latest book is Downsizing
© 2012 Bill Sardi Word of Knowledge Agency, San Dimas, California.
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