You Shake,
Then Freeze
Strategies in the War on Parkinson's
by Roger Martin
A few years back, my Aunt Norma was going to Arcadia,
California, to visit a friend. She and my mother were waiting in the
car for the bus to arrive.
"When it came," my mother says, "I opened the car door
to get out. Aunt Norma didn't. She looked at me and said, 'I can't move.
My body's frozen.'"
How long, my mother asked, before it would unfreeze?
"Sometimes it takes 20 minutes," she said, "sometimes
a half hour."
When the bus drove off, Aunt Norma was not aboard.
That's what it's like with Parkinson's disease.
Aunt Norma's had it for about 30 years.
The death of brain cells causes the symptoms of Parkinson's,
says Raj Pahwa, director of the Parkinson's Disease Clinical and Research
Center at the University of Kansas Medical Center. By the time the first
tremor appears, 75 to 90 percent of the cells that control fine movement
are dead.
Several new treatments show promise, Pahwa says.
The National Institute of Neurological Disorders and
Stroke, or NINDS, had, as one of its three initiatives in federal fiscal
year 2000, a focus on deep-brain electrical stimulation to help people
with Parkinson's. In this form of therapy, a thin wire is slipped into
the brain to a precise target -- a region called the subthalamic nucleus.
Tiny pulses of electricity calm the region and diminish the disease's
symptoms.
But the brightest star on the therapeutic horizon for
Parkinson's patients, according to Pahwa, also turns out to be one of
the most controversial. It involves stem cells.
These immature cells, first isolated
by scientists a few years ago, can be treated and transformed into any
kind of cell in the body, including brain cells. The dream is to grow
brain cells in the laboratory, then implant them in patients to replace
the dead cells.
Stem-cell research is controversial because the best
source of stem cells is the embryos discarded daily by clinics that
help couples have babies.
Despite political pressure to
disallow the use of stem cells from these embryos, the National Institutes
of Health last year announced that it would fund studies using stem
cells.
Here's more about Parkinson's disease from a recent
interview with Pahwa.
Q: NINDS finished a five-year plan related to Parkinson's
in 2000. The disease is fairly uncommon, right? Why is it such a focus?
A: It's a rare disease but more common than multiple
sclerosis, for example. Among neurological diseases, it comes right
after stroke and Alzheimer's. About 2 million people have it, and 30
to 40 percent of those are undiagnosed.
Q: Why?
A: They haven't seen a physician about symptoms. They
believe they're just getting old.
Q: Is tremor the usual symptom that gets people
to a doctor?
A: That's true in about two-thirds of the patients.
It usually starts on one side of the body. It's mainly a tremor that
occurs when a person is relaxed and in a resting position. The hand
shakes or trembles. Sometimes patients experience an internal shakiness.
Q: What other signs and symptoms are there?
A: Slowness. Difficulty walking. Stiffness. Chronic
fatigue -- that goes with any neurological disease.
Q: Because there's brain damage, can a brain scan
reveal the nerve cell damage that leads to Parkinson's?
A: Not yet. That's only at the research stage. A Parkinson's
diagnosis is made clinically.
Q: I've heard that taking some of the new antidepressants
like Zoloft or Prozac can cause tremor.
A: With those drugs, you may get tremor but not the
stiffness and slowness of Parkinson's.
Q: Something like 75 to 90 percent of the cells
that control fine movement must be gone before a person presents symptoms.
How can so few cells keep us going?
A: Everything we do requires a very small amount of
our cells. We don't use that many muscle or brain cells to function.
There's tremendous rendundancy in the body.
Q: Deep-brain stimulation with an electrode is one
of the disease control approaches that NINDS is using. Is there actually
a wire inserted into the brain?
A: Yes. You can find out more about it at our homepage:
http://www.kumc.edu/parkinson/.
Q: Is deep-brain stimulation being tried with other
disease?
A: With epilepsy and some other things, but that's
outside my expertise.
Q: What's the theory about why it works?
A: Essentially, you're making a functional lesion in
the brain and resetting the brain circuitry. You're decreasing the excitation
in a part of the brain called the subthalamic nucleus.
Q: I've heard that very near the region that is
electrically stimulated there's also a region related to despair and
anxiety. Gerald Fischbach, the head of NINDS, described a video of a
patient who was stimulated, inadvertently, in that region and just wanted
to die -- until the stimulation was halted. Fischbach said the area
was only 2 millimeters shy of the target region. That's less than a
tenth of an inch.
A: Yes, missing by that much can lead to acute depression.
We've also seen people laugh when the wire touches certain regions.
We don't know much about these phenomena. Certain functions are highly
localized in the brain.
Q: How is the electrode inserted?
A: The neurosurgeon knows when he's reached the right
point because of readings that come back from the tip of the electrode.
He also relies on MRI (magnetic resonance imaging) maps to determine
how deep in the brain he needs to go to get to the structure.
Q: How big is the target?
A: Less than a centimeter in diameter. About the size
of a pea.
Q: Fischbach says there are several areas where
there's real hope of revolutionary progress in treatment of Parkinson's.
Where do you think the greatest hope lies?
A: I think the stem-cell research is the best hope.
The work is still in its infancy, but we believe that cells at certain
early stages in their development can, with the right stimulus, be transformed
into any kind of cell in the body -- including brain cells.
If we could grow dopamine-producing cells in the laboratory
-- it's a dopamine shortfall in the brain that causes the symptoms of
Parkinson's -- then we could implant them in the brain where they'd
function as normal dopamine-producing cells.
Remember though: Even if we can grow these cells in
a dish, we still have to get them to work in the brain.
Q: Why do you think this is the best hope in Parkinson's
research?
A: Because you're actually reversing the pathology
in the brain -- remodeling the brain itself.
Q: The old-fashioned helper is the drug L-dopa.
How does it work?
A: It's converted by the brain into dopamine.
Q: What are the downsides?
A: You have long-term side effects. Involuntary movements.
And then sometimes the medication works and sometimes it doesn't.
Q: I hear about cell-replacement therapy -- putting
cells into the basal ganglia region, cells that make dopamine. Is that
stem-cell work?
A: Fetal cells and pig cells are also being tried.
Q: And how are those cells delivered to the brain?
A: They're injected.
Q: What's your research?
A: In our clinic, we're testing a new form of L-dopa
that's fast acting. We're working with a compound that's supposed to
regenerate brain cells and a couple of drugs that produce dopamine-like
effects. We're also testing a drug available for Lou Gherig's disease
that may slow the disease process in Parkinson's.
As far as surgical therapy, we're monitoring the effects
of deep-brain stimulation.
Q: How do things look today, compared with 20 years
ago?
A: Much more promising. That's because more research
is being done and much more money is being given to Parkinson's research.
