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-----Original Message----- 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/ >[log in to unmask] >