Parkinson's disease: The silent epidemic
Thursday, April 1, 1999
By CAROL SMITH P-I REPORTER
SEATTLE POST-INTELLIGENCER REPORTER
Parkinson's disease is a cruel magician. It makes its victims slowly
disappear.
It mutes their voices, erases their expressions, robs them of their motor
control. Finally, they freeze in a kind of suspended animation, disappearing
behind the blank stare of the "Parkinson's mask."
         See also:  Parkinson's disease: The silent epidemic
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Parkinson's, scientists get breakthrough <../local/mptp01.shtml>
Although more people have Parkinson's than multiple sclerosis, Lou Gehrig's
disease and muscular dystrophy combined, the disease has escaped much public
notice and research funding.
It is a disease that renders its victims invisible, trapping them inside
their houses, inside their bodies, inside their minds, until they simply
vanish to the rest of us.
``Parkinson's has been called the silent epidemic,'' said Dr. Donald Calne,
a neurologist at the University of British Columbia in Vancouver. And it's a
growing one.
But researchers are optimistic. Breakthroughs are on the horizon that they
hope will not only help Parkinson's patients, but also will advance the
understanding of other degenerative brain diseases. New drugs and new kinds
of surgery that could dramatically improve quality of life are becoming
available.
Once thought of exclusively as an ``old person's disease,'' Parkinson's is
increasingly affecting younger people.
Scientists aren't sure why. Possibly, greater awareness of symptoms has led
to earlier diagnosis. But it may be something more sinister.
Parkinson's is caused by a shortage of a chemical messenger in the brain.
Dopamine, a key neurotransmitter involved in motor control, allows us to
translate the will to move into action. What causes brain cells to die and
stop producing dopamine, however, remains a mystery.
Scientists suspect that the disease is caused by a complex interaction
between genes and the environment. Environmental toxins play a role in
triggering the disease, although no one knows which toxins, or why they
trigger the disease in some people and not others.
Many believe that until those answers are clear, the incidence of
Parkinson's is bound to increase.
Calne, who has tracked Parkinson's patients for more than three decades, has
already seen a fourfold increase in younger patients.
Although the average age of onset is about 57, 10 percent to 15 percent of
patients show symptoms before 40.
An estimated 1 million people _ 1 percent to 2 percent of people older than
60 _ have Parkinson's disease, a number that is expected to swell as baby
boomers age.
And it could get much worse. Some experts call Parkinson's the ``iceberg
disease.''
Autopsy findings show that for every patient with overt symptoms of
Parkinson's, 10 or 20 more show traces of the brain damage associated with
the disease.
Despite its prevalence, Parkinson's hasn't had the visibility of illnesses
such as AIDS or cancer, partly because patients haven't mobilized to raise
money or awareness.
It's hard to get Parkinson's patients to take action, said Dennis Wright,
46, who was diagnosed four years ago. Parkinson's patients can't turn their
own thoughts into actions, let alone act on the thoughts of others.
``Not responding is pretty natural in this group,'' he said. Wright has
lobbied in Washington, D.C., as well as Olympia to raise funds to fight the
disease.
``We're still way behind on per-patient spending compared to other
diseases,'' Wright said.
Parkinson's affects about as many patients as HIV and AIDS, for example, but
the National Institutes of Health last year spent $41 in research dollars
per Parkinson's patient, compared with $1,640 per patient with HIV or AIDS.
Now more and more Parkinson's patients, especially younger ones, are
speaking out about the need for more funding in the hopes of finding a cure.
A Parkinson's cure also could yield new approaches to treating other brain
diseases, such as Alzheimer's and Lou Gehrig's disease.
``There are so many possible cures coming from so many different
directions,'' Wright said. ``People always say a cure is 15 years away, but
my goal is to get that to five years, or three years even.''
OIL FOR THE TIN MAN:
A cure has already come tantalizingly close.
Dr. James Parkinson first described the mysterious ``shaking palsy'' in
1817. Although references to Parkinson's symptoms date to Chinese and Indian
medical texts more than 2,500 years ago, Parkinson was the first to
recognize that many paradoxical symptoms were related to the same disease.
The symptoms included stiffness and tremors, rigid immobilization and a
sudden unlocking of activity. Patients might sit for hours with an
unblinking stare, or suddenly scoot off in a frenzy of tiny, accelerating
steps, a stuttering gait that gave them a Chaplinesque quality. Apparently
paralyzed, many patients were nonetheless capable of surprising reflexive
action, such as running out of a house on fire, or jumping in a river to
save a drowning victim.
It was as though some internal on-off toggle switch was malfunctioning.
It took 150 more years for scientists to figure out that the toggle switch
was dopamine, which is vital for relaying motor signals in the brain.
``Dopamine is like oil for the tin man,'' said Bill Bell of Seattle, whose
mother, stepfather, godfather and another relative all live with the
disease. Dopamine is what keeps people moving smoothly.
That discovery led to the first treatment for Parkinson's: levodopa. L-dopa,
made famous in Oliver Sacks' book ``Awakenings,'' is converted to dopamine
by nerve cells in the brain.
L-dopa miraculously roused Parkinson's patients _ even some who had been
frozen for decades _ but the ``cure'' was short-lived. As Parkinson's
progresses, there are fewer neurons to convert L-dopa to dopamine, and the
drug's efficacy wears off.
Parkinson's symptoms occur when dopamine-producing neurons in the substantia
nigra of the brain begin to die. In the exotic geography of the brain, the
substantia nigra is a thumbnail-size structure at the top of the brain stem
in one of the most primitive and evolutionarily ancient parts of the brain.
The neurons of the substantia nigra communicate with the basal ganglia _ a
constellation of neuron-dense structures buried deep in the cerebral
hemispheres.
The basal ganglia provide a critical feedback loop that governs motor
control, modulating information as it flows between the cerebral cortex,
where complex movements originate as thoughts, and the spinal cord, where
those thoughts are translated into action. Dopamine makes this loop work,
giving people control over their voluntary movement.
By the time symptoms appear in most patients, the brain has already lost 80
percent of its ability to make dopamine.
Without dopamine, the nerve cells can't tell which signals are important to
relay, said Richard Palmiter, a professor of biochemistry at the University
of Washington.
``Suppose you're driving at night and you see hundreds of lights, but you
can't figure out that the red and green lights are the important ones to pay
attention to,'' he said. ``Somehow, you've got to be able to focus on the
right lights, or you'll make the wrong decision when driving.''
Dopamine helps direct the nerve cell traffic.
THE SEARCH FOR CLUES:
Although researchers don't know what causes neurons in the substantia nigra
to die, they suspect genetic susceptibility and environmental toxins both
play a role.
A landmark study published recently in the Journal of the American Medical
Association, for example, showed that the identical twins of Parkinson's
patients are no more likely overall to get the disease than non-identical
siblings, indicating that genes play a limited role. (There was evidence
that genetics play a stronger role in patients who show symptoms before age
50.)
``Parkinson's is thought to be caused by the combination of aging, genetic
predisposition and environmental factors,'' said Dr. Ali Samii, a
neurologist and movement disorder specialist at Harborview Medical Center in
Seattle. Except in rare cases, it doesn't run in families. But about 15
percent of patients have a close relative with Parkinson's, which points to
a complicated interplay between environment and genes.
``We think something quite transient might set (the disease) in motion,''
Calne said. ``That's the simplest explanation. Some (environmental factor)
kills some cells immediately and damages others.''
An environmental trigger could alter the programming of the cells so they
die over time, eventually depleting the dopamine supply.
``Rough epidemiological studies have linked higher incidence of Parkinson's
in areas of high industry, or where there is lots of chemical usage,'' said
Dr. Phil Ballard, director of the Movement Disorder Center at Swedish
Medical Center. ``Some studies have linked it to well water as well, but so
far no one has been able to identify any one specific thing.''
TREATMENT HORIZONS:
While scientists continue to search for the trigger, they also are devising
new ways to treat Parkinson's.
``What's exciting about Parkinson's is that the knowledge about the
mechanism underlying nerve cell degeneration and regeneration is just
exploding,'' Ballard said.
Many scientists believe that Parkinson's research will yield the big
breakthrough that will allow them to someday reverse many kinds of
degenerative brain diseases.
Work already is under way on new classes of drugs, including some that
doctors hope will be neuroprotective _ preventing the nerve cells from dying
in the first place.
``This is a rather exciting time,'' Calne said. ``In the course of the last
two years, five new drugs for Parkinson's have come on the market, compared
with about one every five years previously.''
Three of the new drugs mimic the action of dopamine, and two block the
breakdown of dopamine so that the brain's supply doesn't dwindle as quickly.
Some researchers are looking at ways to stimulate the brain to make new
neurons, something thought impossible a few years ago, Ballard said.
In the meantime, new surgical techniques show promise for better symptom
control, especially for tremors. Dr. Sean Grady, a neurosurgeon at
Harborview, and Dr. Diana Kraemer at Swedish are doing ``deep brain
stimulation,'' which involves threading a delicate electrode into the
thalamus, one of the structures of the basal ganglia. The electrode is
attached to a pacemaker-like device implanted in the patient's chest. The
patient activates the device by passing a magnet over his skin. The device
then delivers a mild electrical current that essentially ``turns off'' the
tremor by blocking nerve cells that are misfiring in the brain.
The device can be ``tuned'' up or down, depending on the tremors' severity,
and generally creates fewer side effects than traditional surgery for
tremors. It also is reversible. Surgeons can remove the electrode, leaving
the brain tissue intact. In the traditional approach, surgeons burn small
lesions in the brain, permanently destroying tissue, Grady said.
As techniques improve, scientists also are experimenting with threading the
electrodes into an even smaller part of the brain _ the subthalamic region _
which they think could control even more Parkinson's symptoms.
There are even more futuristic therapies on the horizon. Scientists now
believe that fetal cells implanted in the brain can replace the missing
dopamine. For such implants to become widespread , however, researchers must
develop a cell line that can be cultured in the lab and produced in large
quantities.
Even more enticing is the lure of gene therapy.
The UW's Palmiter recently demonstrated a technique for introducing new
genes into the brain cells of mice, which could lead to gene therapy.
Palmiter used a modified virus to introduce a gene that caused mice with
Parkinson's-like symptoms to make more dopamine. Viruses, which are nature's
genetic engineers, can insert themselves into the DNA of host cells.
The trick is to find the right gene to put into human brain cells, Palmiter
said. Researchers are looking for a gene that would protect the cells in the
substantia nigra from being destroyed by Parkinson's.
To find such a gene, however, scientists need to understand how the cellular
machinery breaks down in the first place. This is the holy grail of brain
research. Scientists now think there may be a common mechanism that causes
cell death in patients with Alzheimer's, Lou Gehrig's disease, Progressive
Supranuclear Palsy and other neurodegenerative brain disorders.
``Alzheimer's and Parkinson's _ they have common threads running through
them,'' Calne said. ``If patients live long enough with Alzheimer's, they
will develop some symptoms of Parkinson's and vice versa.''
Researchers hope unlocking the secret to Parkinson's will help unlock the
secret to all the degenerative brain diseases.
``We have pieces of information,'' Ballard said. ``It's like a picture
developing in a (darkroom) pan. The picture is just starting to get to where
you can tell what it is.''
P-I reporter Carol Smith
can be reached at 206-448-8070


Bill Bell
Executive Director
Northwest Parkinson's Foundation
425-746-5556 / [log in to unmask]
http://www.nwpf.org