At 01:39 PM 6/18/98 , you wrote:
>Hi Jerry: Today's San Francisco Chronicle gives a website you might want to
>check out????? http://www.caregiver.org/
>
>Among other things there's an encouraging article by Dr. Langston
>
>Best, Liz S~~
>
For those without browser capability, here's the Langston article:
Dr. J. William Langston, M.D. is President of the
Parkinson's Institute. A graduate of the
University of
Missouri Medical School, he completed his
internship and residency in Neurology at Stanford
Medical School and received additional training at
the Meninger Foundation in Topeka, Kansas, and
the National Institute of Neurology in London,
England. He has served as chief of the Department of
Neurology for the Santa Clara Valley Medical
Center, as a member of the faculty at Stanford
University, and as a Senior Scientist with the
California Institute for Medical Research. A
diplomate of the American Board of Psychiatry and
Neurology, Dr. Langston has authored over 180
publications, mainly in the areas of Parkinson's
disease, neurotoxicology and pharmacology, aging,
movement disorders, and neurodegenerative
diseases. Dr. Langston is also the co-author of The
Case of the Frozen Addicts, a book which
describes the discovery of MPTP.
What is the Parkinson's Institute and how was it
started?
The Parkinson's Institute is a nonprofit
organization
that represents a unique blend of clinical research,
basic research and day-to-day patient care. We have
one of the largest movement disorders clinics in
north
America, but also have a full basic research
laboratory where almost every aspect of the disease
is under study. What's quite powerful about this
approach is that discoveries in the laboratory can
quickly be translated to the clinic and vice
versa --
observations in the clinic can be taken to the
laboratory for further study. So it is a very
effective
way to do disease-oriented research and from that
standpoint it's a fairly unique organization.
How long has the Institute been in existence?
This is our tenth anniversary. We were founded in
1988. We started in a small one-room trailer but
have since developed into a fully integrated,
multidisciplinary institute with a mission of
finding the
cause and cure of Parkinson's disease.
Would you give us a definition of Parkinson's
disease?
Parkinson's disease is one of the two major
degenerative diseases of the brain associated with
aging. Alzheimer's disease is the other.
Different from
Alzheimer's, however, is the fact that Parkinson's
disease robs patients of their ability to move
normally
and in the majority of the cases, leaves thinking
intact. The disease is slowly progressive and
there is
no known cure for it at the current time.
Clinically, it
is associated with a variety of motor symptoms
including slowness of movement, difficulty with
walking (typically characterized by a slow,
shuffling
gate), tremor which occurs at rest, and a loss of
balance causing patients to have a tendency to
fall.
There are a wide variety of treatments now
available for Parkinson's disease as opposed to
Alzheimer's where there is really very little. In
fact, it
would be fair to say that the major enemy in
treating
Parkinson's disease at the current time is probably
less the ability to manage symptoms, than it is to
avoid side effects of the drugs we use to treat it.
These side effects of therapy often force us to
decrease doses of medication at a time when patients
actually need it more than ever. So, a lot of
what we
do in treating Parkinson's disease is directed as
much
towards avoiding the side effects of therapy as
it is to
try to make the patient better on a day-to-day
basis.
What are some of the current treatment
protocols?
There are a variety of medications available for
Parkinson's disease. The backbone of therapy is
still
L-DOPA, commercially available as Sinemet and
also in generic forms. Very few patients can go
for a
long period of time without L-DOPA after the
diagnosis of Parkinson's disease is made. L-DOPA
is called a dopamine precursor because the brain
converts it into dopamine. Dopamine is depleted in
the brain of patients with Parkinson's disease.
It is
not possible to give dopamine directly because it
does not cross the blood brain barrier, whereas the
precursor L-DOPA does.
A second class of drugs used to treat Parkinson's
disease are the so-called dopamine agonists. These
are completely different compounds that do not
require transformation into dopamine, but rather
stimulate dopamine receptors directly. Agonists tend
to be longer acting than L-DOPA, and tend to both
accentuate and smooth out its effects. Currently
available agonists include bromocriptine (Parlodel),
pergolide (Permax), pramipexol (Mirapex) and
ropinerol (Requip).
In addition to L-DOPA and dopamine agonists,
there are a number of other pharmacologic
approaches to the disease. Anticholingeric agents
represent another of the class of drugs used to
treat
Parkinson's disease, but they are less used now
because of their side-effects, particularly on
memory
and thinking. Another category of drugs are
monoamine oxidase inhibitors. One of these, known
as selegiline (Eldepryl), has been suggested to slow
the progress of Parkinson's disease. While this
remains to be unequivocally proven, because of its
relative safety in newly diagnosed patients who are
not on other forms of treatment, many physicians do
use it early on to try to help slow down the
process.
This drug also makes L-DOPA therapy more
effective by blocking the breakdown of dopamine.
Very recently, an entirely new class of drugs
have
begun reaching the market, called COMT inhibitors.
These drugs block the metabolism of L-DOPA itself
in the periphery and perhaps to some degree in the
brain. There is solid evidence that they enhance the
effectiveness of L-DOPA, possibly with less risk of
side-effects than by simply increasing the dose of
L-DOPA itself. One of these drugs, tolcopone
(Tasmar) is now available for use.
So, we do have large panoply of drugs - the art
of managing Parkinson's is when to start those drugs
and how to apply them to get a longer, better effect
while also avoiding side effects.
What is the length of time that someone would
be on any of these drugs or combinations of
these drugs?
Anyone who has Parkinson's disease, once they
reach a point where they need symptomatic therapy,
is going to be on one or more of these drugs the
rest
of their life. Most patients, once they start
L-DOPA,
will never go off the drug. The agonists tend to be
added later, although in younger patients I start
with
agonists.
Beside the medication management issue, are
there other treatment protocols like direct
therapeutic interventions or other aspects of
caring for patients with Parkinson's that the
Institute is recommending in terms of family
care?
Surgical interventions represent an exciting new
arena
for the treatment of Parkinson's disease. The one
that
is attracting the most interest right now is a
procedure
called deep-brain stimulation. This technique
involves
placing electrodes in specific brain areas, where
they
are left and connected to a pacemaker which is used
to turn the electrodes on and off and set the
stimulus
parameters. This procedure has already been
approved by the FDA for treatment of tremor by
placing the electrode in an area known as the
thalamus. However, a much more exciting possibility
is to use this approach to treat most, if not
all, of the
symptoms of Parkinson's disease by stimulating a
different area of the brain known as the subthalamic
nucleus, bilaterally. In some cases, it has been
possible to dramatically reduce the symptoms of
Parkinson's disease with this type of brain
stimulation, and a few patients have even been able
to stop all antiparkinsonian medications. This
procedure is still experimental, and the long-term
effects and likelihood of obtaining a good or
excellent
response are still unknown. The area of
neurotransplantation is also of interest, but the
research is moving quite slowly, in part at least
because of issues regarding limited supply of
tissue,
and the lack of viable alternatives to fetal
tissue at the
present time.
Moving out of the area of pharmacological and
surgical therapy, there are many things that one can
do for Parkinson's patients. By and large the most
important one in my opinion is exercise. Exercise
has
a very positive effect on a day-to-day function.
Short
of medical therapy, if there's one thing we can
encourage patients to do, it is to participate in
exercise programs - to stay active and to keep their
bodies going. This is a very important point.
Diet is
important. One has to be careful with protein
because it interferes with L-DOPA transport into the
brain. One needs protein to live, so patients can't
stop eating protein, but it is possible to move
protein
intake around during the day to better facilitate
function at other times of the day. Overall, we
really
encourage patients to try to stay active and
maintain
as much of a normal life routine as they can.
Are there other areas of research going on in
the field that you'd like to comment on?
One area that is really important is research on the
cause of the disease. There are now two families
where parkinsonism has been found to be inherited in
a dominant form. When the identity of the
responsible mutation was announced last year, it was
widely reported in the news media that the gene for
Parkinson's disease had been found, and that led
many to believe that their Parkinson's was going to
be passed on to their children. I think it's very
important to emphasize that this genetic form of
parkinsonism is restricted to date to a handful of
families, so far as we know. So, heredity appears to
be a rare cause of Parkinson's disease.
We recently published a study in which we
examined 100 consecutive younger-onset (under the
age of 50) Parkinson's patients for the gene that is
now known to cause a form of parkinsonism. None
of the patients in our study were found to carry
this
gene. So, the gene that has been so widely reported
is actually a very rare cause of the disease. In
fact,
most patients do not need genetic testing and
probably should not worry about their children
inheriting the disease. I would say only in
situations
where there are multiple-affected immediate family
members should it even be considered.
Are there other areas of research and trends
that you see as promising that are in clinical
trials now?
There is one more I would mention that is in the
experimental stage at this time, but could be very
promising and that is the area of using growth
factors.
There are so-called neurotrophic factors that
seem to
stimulate neurons that are not functioning and can
actually protect neurons from damage. There are
now a number of such compounds that have been
found to stimulate dopaminergic neurons. There is
great hope that those compounds might be used to,
for lack of a better word, rejuvenate neurons
that are
damaged or are not functioning in Parkinson's
disease (or, put another way, to turn them back on).
The reason this is so exciting is that there is good
evidence that there are many neurons in the
brains of
Parkinson's patients that have not died yet, but are
no longer functioning. It's conceivable that if you
could turn those neurons back on, you might actually
be able to bring patients back out of a symptomatic
state because there is a fine line as to how much
dopamine you need to lose to get symptoms. So,
there's a lot of interest in the possibility that
these
neurotrophic factors could be used not only to
try to
halt progression but actually, to some degree,
reverse
the symptoms. That's theoretical. There is a lot of
experimental evidence that suggests it could be done
and there is at least one clinical trial
currently going
on in humans to test this hypothesis using a growth
factor known as GDNF.
It sounds like there is a fair amount of study
going on.
If you looked at the field of Parkinson's disease 15
years ago, it was a barren land in terms of
research.
Now we have so many new leads that it is hard to
know which ones to follow. The good news for
patients is that it's a very exciting time in the
history of
Parkinson's disease research and that in the long
run,
this cannot help but benefit patients with
Parkinson's
disease. So stay tuned.
For more information about the Parkinson's Institute,
visit their
website .
