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From: janet paterson <[log in to unmask]>
To: [log in to unmask] <[log in to unmask]>
Date: Monday, June 14, 1999 4:35 AM
Subject: The Latest PD Overview: Harvard Health Letter May 1999


>MEDICAL PROGRESS
>
>New Hope for Parkinson’s Treatments
>
>Ever since the British doctor James Parkinson first described the disease
>that bears his name in 1817, the search for Parkinson’s treatments has been
>marked by both hope and disappointment. In the 1940s and 50s, for example,
>doctors were optimistic that an operation called pallidotomy could reduce
>or halt the tremors, rigidity, and slowed movements that characterize this
>degenerative brain disorder. But their hopes were soon tempered by concerns
>that the procedure carried too high a risk of inflicting severe
>neurological damage.
>
>Because of this, and because of the arrival of the drug levodopa (L-dopa)
>in 1968, pallidotomy was subsequently abandoned. With none of the hazards
>of surgery, L-dopa could control tremor, relieve painfully slow movements,
>and reduce rigidity. Today, the
>most widely used and effective form of the drug is Sinemet, a combination
>of levodopa and a related substance called carbidopa, which helps prevent
>L-dopa from breaking down before it reaches the brain.
>
>However, as more patients were treated with L-dopa over the years, it
>became obvious that the drug has its own share of problems. For reasons
>scientists don’t understand, the medication’s benefits wane. After about
>five years, approximately half of those taking Sinemet fall into an
>"on-off" pattern, in which "frozen" periods of impaired movement
>(bradykinesia) alternate with intervals of excessive and uncontrolled
movement
>(dyskinesia).
>
>Now, scientists and doctors have once again emerged from their labs and
>clinics with a spate of hopeful discoveries - as well as improvements to
>previous therapies. Pallidotomy, for example, has returned in the past few
>years as a much safer procedure, and one that is particularly effective at
>reducing the dyskinesia caused by long-term Sinemet use. Meanwhile, several
>new medications have recently become available that may enhance the
>effectiveness of L-dopa or reduce or delay its use.
>
>Parkinson’s disease is one of several illnesses that cause parkinsonism - a
>term that refers to any condition marked by slow, trembling, or rigid
>movements. But Parkinson’s disease carries a unique neurological signature:
>the selective, progressive death of nerve cells in a small area of the
>brain called the substantia nigra. These specialized cells manufacture the
>chemical messenger dopamine, which is essential for smooth
>and normal movement.
>
>Although Parkinson’s is not a terminal illness, its symptoms worsen over
>time as more and more nerve cells are destroyed. No one knows what causes
>the disease, which affects about 1 million Americans, but older age seems
>to be the most important risk factor. The majority of affected individuals
>are diagnosed after age 65, although about 10% have a less common,
>early-onset form of the disease that strikes before 40.
>
>L-dopa remains the "gold standard" of Parkinson’s treatment; it works by
>increasing the amount of dopamine in the brain. However, because the drug’s
>effectiveness diminishes over time, most doctors recommend delaying
>treatment with Sinemet as long as
>possible and starting with other drugs.
>
>In 1997, the U.S. Food and Drug Administration (FDA) approved two new drugs
>- pramipexole (Mirapex), manufactured by Pharmacia & Upjohn, and ropinirole
>(Requip), from SmithKline Beecham Pharmaceuticals - that may put off the
>use of L-dopa. These
>medications are the latest additions to an existing class of drugs called
>dopamine agonists, which trick the brain into believing there is more
>dopamine on hand than there really is.
>
>The new drugs are approved for both early use as single-drug therapies and
>to be taken in combination with Sinemet later on. All dopamine agonists can
>cause nausea, confusion, and nightmares, but the new drugs are believed to
>cause fewer of these side effects than older members of this class.
>
>In early 1998, the FDA approved tolcapone (Tasmar), the first of a new
>class of Parkinson’s medications called COMT inhibitors. These drugs
>enhance the effectiveness of levodopa by blocking the enzyme
>catechol-O-methyltransferase, which causes L-dopa to break down before
>reaching the brain. Tasmar was initially intended for individuals who were
>responding fairly well to Sinemet as well as those in whom Sinemet’s
>effectiveness had waned.
>
>However, in light of a report issued late last year linking Tasmar to three
>fatal liver injuries, the medication is now recommended only for people who
>do not have severe movement abnormalities and who do not respond to or are
>not appropriate candidates for other available treatments. The report,
>which was released by the FDA and  Hoffman-LaRoche, Inc., Tasmar’s
>manufacturer, also advised anyone taking the drug to have frequent blood
>tests to monitor liver function.
>
>Surgery makes a comeback
>
>Pallidotomy has gained new popularity in recent years. A five-year Harvard
>study presented at a neurological conference last year indicated that about
>70% of 85 Parkinson’s patients who underwent pallidotomy experienced good
>to excellent improvements in mobility. Last year, Medicare agreed to cover
>the cost of the
>surgery, which ranges from $20,000 to $40,000. Only 5%-10% of patients,
>whose symptoms can no longer be controlled by Sinemet, are candidates for
>pallidotomy. Although the surgery won’t cure the disease, it can improve
>slowed movements, rigidity, and
>tremor and lessen the uncontrolled movements caused as a side effect of
>Sinemet. The operation targets one side of the globus pallidus, an area of
>the brain that appears to become overactive in Parkinson’s patients.
>Surgeons use magnetic resonance imaging
>(MRI) to visualize the globus pallidus and then insert an electrode probe
>to destroy a small portion of its cells. Pallidotomy relieves symptoms
>mainly on one side of the body, because operating on both sides of the
>brain is very risky.
>
>Pallidotomy is safer than it used to be due to improvements in imaging
>technology that allow doctors to more accurately target the right area of
>the brain. However, it still carries risks; the most serious complication
>is stroke, which occurs in about 1%-3%
>of cases.
>
>In August 1997, the FDA approved an implanted electronic brain stimulator
>that can reduce tremors in many people with Parkinson’s disease or
>essential tremor, a disorder that causes involuntary shaking but no other
>symptoms. (For more on essential tremor, see Harvard Health Letter, March
>1999.) An electrode is surgically inserted into one side of the thalamus,
>the part of the brain believed to cause tremors. A wire attached to the
>electrode is threaded just under the scalp and connected to a
>pacemaker-like generator implanted near the collarbone. When activated, the
>device sends a constant stream of electrical waves to the brain, blocking
>tremors.
>
>In the genes
>
>In 1997 and 1998, scientists identified for the first time two gene
>abnormalities present in Parkinson’s patients whose families have a high
>prevalence of the disease, indicating that at least some cases are
>inherited. Both abnormalities cause the body to
>produce an altered version of a protein that plays a role in the function
>of nerve cells.
>
>A subsequent study in the January 27, 1999, Journal of the American Medical
>Association suggested that heredity has a major influence in causing only
>the early-onset form of the disease. Researchers led by those at the
>Parkinson’s Institute in Sunnyvale, California, contacted 19,842 male twins
>age 65 and older and identified 172 twin pairs in which at least one twin
>had Parkinson’s.
>
>If the condition is hereditary, the investigators reasoned, the rate of
>twins both having the disease should be lower among fraternal twins, who
>share some but not all of the same genes, than among identical ones, whose
>genetic makeups are exactly alike. In individuals who were diagnosed after
>age 50, the rate of twins who both had the disease was similar among
>fraternal and identical twins. However, in those diagnosed at 50 or
>younger, the rate was much lower in fraternal twins.
>
>Making the diagnosis
>
>Unfortunately, there is no single test that can nail down a Parkinson’s
>diagnosis. Instead, doctors make the call based on the presence of tremor,
>stiffness, and slowed
>movement. However, this often leads to misdiagnosis, since many other
>conditions - including essential tremor, drug-induced parkinsonism, and
>arthritis - can cause similar symptoms.
>
>For the past ten years, scientists around the world have been working to
>find a way to visualize the characteristic loss of dopamine-producing cells
>that occurs in the brains of Parkinson’s patients. In one line of research,
>Harvard investigators identified a chemical called altropane, which binds
>to dopamine nerve cells and lights them up on a special imaging instrument
>- a single photon emission computed tomography (SPECT) machine. After being
>injected with a small amount of altropane, a person would place her or his
>head in the machine, which visualizes the brain. Meanwhile, Yale
>researchers have been studying another promising imaging agent, called
>beta-CIT, which could also be
>used with SPECT to identify Parkinson’s.
>
>SPECT instruments can be found in almost every medical center in the
>country, and doctors are currently testing the safety and effectiveness of
>altropane and similar agents. Thus, a reliable diagnostic test for
>Parkinson’s disease could be a reality within a few years.
>
>On the horizon
>
>Researchers are currently investigating a number of agents that they hope
>can somehow prevent dopamine-producing nerve cells from dying. One such
>compound, called glial-derived neurotrophic factor (GDNF), is a naturally
>occurring substance that has been found to markedly improve Parkinson’s
>symptoms in animal studies. GDNF is currently being tested in human trials
>of individuals with advanced Parkinson’s.
>
>Another experimental approach involves transplanting dopamine-producing
>human or pig fetal cells into the brains of Parkinson’s patients. In
>preliminary studies, these transplants improved patients’ symptoms for up
>to two years and enabled some of them to lower their dose of L-dopa.
>However, this field of inquiry is plagued by controversy; opponents argue
>that the use of human fetal tissue is morally wrong and that using pig
>cells could pose unknown risks.
>
>Several research teams are currently experimenting with genetically
>engineered skin cells and a variety of other human and animal cells that
>can be "taught" to produce dopamine. Cell transplantation is a hot area of
>investigation, but its benefits
>will probably not be available to Parkinson’s patients for many years.
>
>Although doctors still don’t know what causes Parkinson’s or how to cure
>it, research efforts to find treatments to slow, halt, or even reverse the
>disease’s relentless progression are more active than ever before. There
>will be setbacks, of course. But for both investigators determined to find
>answers and individuals living with the disease, hope springs eternal.
>
>
>References:
>
>Lang AE and Lozano AM. Medical Progress: Parkinson's Disease,
>First of Two Parts. New England Journal of Medicine, October 8,
>1998, 339: 1044-53.
>
>Lang AE and Lozano AM. Medical Progress: Parkinson's Disease,
>Second of Two Parts. New England Journal of Medicine, October 15,
>1998, 339: 1130-43.
>
>Tanner CM, et al. Parkinson's Disease in Twins: An Etiologic
>Study. Journal of the American Medical Association, January 27,
>1999, 281: 341-46.
>
>Web sites:
>
>American Parkinson's Disease Association at
>     <http://www.apdaparkinson.com>
>
>National Institute of Neurological Disorders and Stroke at
>     <http://www.ninds.parkinson.org>
>
>National Parkinson Foundation Inc. at
>     <http://www.parkinson.org>
>
>
>Harvard Health Letter
>Volume 24 Number 8 June 1999
>Editor-in-Chief Stephen E. Goldfinger, M.D.
>Editor Leah R. Garnett
>Web related inquiries: [log in to unmask]
><http://www.harvardhealthpubs.org/Ltxt.html>
>
>janet paterson
>52 now / 41 dx / 37 onset
>PO Box 171  Almonte  Ontario  K0A 1A0  Canada
>a new voice http://www.geocities.com/SoHo/Village/6263/
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