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 .