11/16 1905 Reno's Announcement Raises Visibility of ... MINNEAPOLIS, Minn., Nov. 16 /U.S. Newswire/ -- In light of Attorney General Janet Reno's announcement that she has been diagnosed with Parkinson's disease, the American Academy of Neurology (AAN) wants to reinforce the need for increased funding for research of neurological conditions such as Parkinson's. "While tremendous breakthroughs have been made recently, there is still much to learn," said the AAN. According to the AAN an estimated 1 million people in the United States have Parkinson's disease, a slowly degenerative neurological disorder that doctors believe is related to a chemical imbalance in the brain. Primary symptoms of this disease include stiffness, tremor, difficulty in initiating movement and loss of balance. Parkinson's affects both men and women, generally 40 years of age or older. According to Dr. Cheryl H. Waters, a neurologist and a Parkinson's expert at the University of Southern California, "There are a lot of treatments and a wide array of medications available to treat Parkinson's disease. However, we need more research funding to find a cure for this disease." "Even though there is no cure at this time, people with Parkinson's disease continue to make valuable contributions to society," the AAN said. Many years may pass before early symptoms progress to the point where they interfere with normal activities. ------ Editor's Note: More information and interview opportunities are available by contacting the American Academy of Neurology at 612-623-8115. 11/16 1838 DRUG THERAPY TO MANAGE PARKINSON'S DISEASE NEW YORK, Nov. 16 /PRNewswire/ -- More than one million Americans suffer with Parkinson's disease (PD), a chronic, progressive neurological disorder that affects motor function, according to the American Parkinson's Disease Association (APDA). Although there is no cure for Parkinson's disease, there are prescribed medications that can help minimize the patient's symptoms -- and perhaps slow the progression -- of the disease. There are a variety of anti-parkinsonian medications that reduce the severity of PD symptoms, thereby increasing patient ability to function. The number and severity of symptoms vary widely among patients, as does individual response to treatment. Accordingly, physicians may prescribe one of the anti-parkinsonian medications or a combination, depending upon each patient's condition. It is very important that open, ongoing communication exists between physicians and patients, so that together they can determine the most successful treatment regimen. Patients who ask questions and find out all they can about the disease will be better able to take control of their disease. All medications currently used to manage PD have one common effect: to minimize the imbalance between two chemicals in the brain -- dopamine and acetylcholine. Balance between the messages from these two chemicals is necessary for smooth, controllable body movements. Some anti-parkinsonian treatments may lose their efficacy over time. Usually, physicians work to control symptoms with small doses of the least powerful drugs, leaving the more potent drugs for later stages of the disease. Because treatment is individualized, physicians will constantly change dosages and combinations of anti-parkinsonian medications over time. Effects of these drugs can often be complementary when used in combination. However, some anti-parkinsonian drugs may cause side effects that may be mistaken for PD symptoms. In all cases, the physician and patient must weigh the benefits of treatment against the potential side effects when determining appropriate therapies. Currently, physicians work with a number of medication categories to control PD: Dopamine Replacement Use of sustained release Sinemet(R) CR (carbidopa/levodopa, controlled-release)/Sinemet(R) (carbidopa/levodopa) has become the standard treatment for PD in the United States. Because PD impairs the ability of the substantia nigra, a tiny patch of cells located on the midbrain, to produce dopamine, the goal of carbidopa/levodopa therapy is to provide this neurotransmitter from an outside source. Dopamine is necessary for normal movement, balance, posture and muscle tone. The drug used for this therapy, levodopa, when given orally, is converted to dopamine. Sinemet CR is indicated to help control Parkinson's disease motor symptoms (e.g., tremor) and may allow PD patients to participate in normal daily activities. However, because prolonged use sometimes can result in negative side effects and a "wearing off" phenomenon, many physicians traditionally withheld Sinemet CR/Sinemet therapy until symptoms worsened. Levodopa, developed in the 1960s, was the first significant treatment for Parkinson's disease. It is the same drug neurologist Oliver Sacks, M.D., gave to his post-encephalitic patients who experienced parkinsonian-like symptoms, as was dramatized in the film, "Awakenings." Today, levodopa is given together with carbidopa, whose function is to inhibit the conversion of levodopa to dopamine outside the brain (e.g., in the peripheral tissues) so that less levodopa is needed in order to achieve a pharmacologic effect. The administration of carbidopa and levodopa together also contributes to a reduction of side effects, such as nausea, which may occur when levodopa is given alone. Sustained-release Sinemet(R) CR (carbidopa/levodopa) and Sinemet(R) (carbidopa/levodopa) are two agents that contain fixed ratios of this carbidopa-levodopa combination that can maximize the benefits of therapy while reducing the side effects. The sustained-release formulation was developed to provide smooth, steady plasma levels of levodopa, thus reducing the motor fluctuations that are characteristic of PD. In addition, it allows most patients to take fewer doses per day. The most common side effects of Sinemet and Sinemet CR are nausea and dyskinesia. When patients begin dopamine replacement therapy, the effects of a dose of medication usually last until the next dose is scheduled to be taken. As the disease progresses, however, some patients begin to experience motor fluctuations. The use of the sustained-release formula of carbidopa/levodopa minimizes this phenomenon, which may allow the patient to participate in normal daily activities. Preventing Dopamine Breakdown One of the most recent developments in PD treatment is Eldepryl(R) (selegiline hydrochloride), also referred to as deprenyl. At the recommended dosage of 10 mg per day, selegiline is a selective inhibitor of monoamine oxidase type B (MAO-B). MAO-B is an enzyme that breaks down the chemical dopamine in the brain. Eldepryl, as an MAO inhibitor, prevents this breakdown from happening and allows dopamine to remain available in the brain for a longer period of time. By blocking the breakdown of dopamine, selegiline prevents a further reduction in the dopamine supply. Eldepryl is indicated as an adjunct in the management of Parkinson's disease patients being treated with Sinemet CR/Sinemet. Eldepryl may help to control/delay the need for Sinemet CR/Sinemet dose increases, while maintaining functional ability over time. By controlling Sinemet CR/Sinemet dose increases, Eldepryl will help minimize Sinemet-related side effects and extend the length of time Sinemet CR is effective. Minor side effects of selegiline include nausea, dizziness, and dyskinesia (involuntary movements). In addition, the breakdown of dopamine by MAO-B can lead to the formation of byproducts called free radicals. Free radicals are a normal part of human metabolism but, in excess, they may actually lead to the destruction of dopamine-producing neurons in the brain, thus worsening parkinsonian conditions. By blocking MAO-B and slowing dopamine breakdown, selegiline may prevent the formation of free radicals and potentially slow the death of dopamine-producing neurons. (The role of free radicals in PD is not yet proven and theories are based upon published scientific data. Data supporting the role of selegiline in slowing the loss of neurons are from an ongoing laboratory study. Eldepryl is not indicated to slow the loss of neurons and clinical relevance of data continues to be investigated.) Reducing Acetylcholine Messages Anticholinergics target the chemical acetylcholine, a neurotransmitter that helps send messages within the brain and throughout the body. While scientists know that acetylcholine assists the function of muscles and some organs such as the heart, they don't fully understand this chemical's role in the brain. It is known that acetylcholine acts as an excitatory substance in the brain -- too much of this transmitter leads to message transmission rates that are above normal levels. Anticholinergics are usually the first medications prescribed in the treatment of PD. These medications may control symptoms effectively for the first three months after diagnosis, and may help some patients for up to two years. Studies demonstrate anticholinergic therapy works for fifty percent of PD patients, usually improving symptoms -- mainly tremor and rigidity -- by 30 percent. By blocking the action of acetylcholine, anticholinergics reduce tremor and rigidity by compensating for the lack of dopamine in the brain. Some side effects can include dry mouth, blurry vision, dizziness and digestive problems and some patients find that these agents often are ineffective in controlling bradykinesia or walking and balance problems. Commonly used anticholinergics include Artane(R) (trihexyphenidyl HCL), Cogentin(R) (benztropine mesylate) and Symmetrel(R) (amantadine HCL). Stimulating Dopamine Dopamine agonists are medications similar enough to dopamine to mimic its action and stimulate neurotransmission directly, sending messages to the body to move. There are two dopamine agonists available for PD treatment -- Parlodel(R) (bromocriptine mesylate) and Permax(R) (pergolide mesylate). Clinical studies show that when dopamine agonists are prescribed in combination with levodopa/carbidopa, symptoms may improve from 10 to 50 percent. Traditionally, dopamine agonists have been used to supplement carbidopa/levodopa. The medications may also delay or prevent long-term carbidopa/levodopa side effects. Side effects of bromocriptine are orthostatic hypotension (a drop in blood pressure usually experienced by the patient as dizziness), nausea, as well as a tendency toward confusion and hallucinations. Side effects of pergolide are dyskinesia, nausea, dizziness, confusion and hallucinations. Future Therapies One therapy that recently has gained attention is the use of fetal tissue implants. This experimental and controversial surgery involves the transplanting of fetal substantia nigra cells into the PD patient's brain. The hope is that these cells will become implanted in the brain and produce dopamine. The surgery has shown some success, but additional research is necessary to fully determine the efficacy of the procedure. In addition, the fields of genetics and biotechnology have uncovered some pieces to the Parkinson's disease puzzle, but it likely will be years before these technologies have an appreciable effect on current PD therapies. Until a cure for Parkinson's disease is found, patients and physicians must continue to pursue treatments that reduce the symptoms of the disease and perhaps slow its progression. With the help of these therapies, patients now are able to take control of PD and continue to live productive lives long after the diagnosis. -0- 11/16/95 /NOTE TO EDITORS: Physicians are available for commentary./ /CONTACT: Sandra Perez, 212-880-5231, or Rona Gurin, 212-880-5252, both of Ogilvy Adams & Rinehart/ CO: American Parkinson's Disease Association ST: New Jersey IN: MTC SU: