Parkinson's Disease: New Treatments Slow Onslaught of Symptoms |
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Although the tag is lighthearted, the awkward and dangerous dilemma he often faces as his lower limbs simply lock in mid-stride is not. At these moments, his body halts abruptly like a movie freeze-frame, and the only way he can walk is to step backward. "I've gotten to where I can move pretty fast in reverse," says Illinois resident Dulaney, 65, whose finessed footwork helps him cope with one of many symptoms of Parkinson's disease. Nationwide, as many as 1.5 million people suffer from Parkinson's, according to the Parkinson's Disease Foundation. A chronic and progressive disorder, Parkinson's strikes slightly more men than women and more whites than blacks in the United States. Though the disease is found most often in patients over 50, as many as 10 percent of patients--afflicted with the so-called "young-onset" Parkinson's--are under 40. About 50,000 Americans are diagnosed with Parkinson's yearly, according to the National Institute of Neurological Disorders and Stroke, which estimates that the total cost of health care for Parkinson's patients will exceed $5.6 billion this year. The Food and Drug Administration has approved nearly a dozen drugs for treating Parkinson's, three of which have been put on the market just in the past year. Also approved in 1997 was a device that is surgically implanted in the brain to lessen the violent shaking experienced by some Parkinson's patients. The 1996 discovery of a gene believed responsible for a form of Parkinson's may result in future innovative treatments. Despite the range of therapies available to ease the disease's debilitating symptoms, however, treatments now on the market can neither replace the faulty nerve cells that cause the disease nor stop Parkinson's from progressing. Numerous public figures have acknowledged their battle with Parkinson's. Attorney General Janet Reno, evangelist Billy Graham, former boxer Muhammad Ali, and former Alabama governor George Wallace all are fighting the disease. Chinese leader Deng Xiaoping was in the late stages of Parkinson's when he died in 1997 at age 92. Parkinson's also gained attention last year with passage of the Morris K. Udall Parkinson's Research Act, which authorized $100 million for Parkinson's research. At press time, the funds had not yet been appropriated. Udall, who has Parkinson's, served in the House of Representatives for 30 years. What Is It? Parkinson's Disease is one of a larger group of
neurological conditions called motor system disorders. Historians have found evidence of
the disease as far back as 5000 B.C. It was first described as "the shaking
palsy" in 1817 by British doctor James Parkinson. Because of Parkinson's early work
in identifying symptoms, the disease came to bear his name. Symptoms usually show up in one or more of four
ways: Though full-blown Parkinson's can be crippling or disabling, experts say early symptoms of the disease may be so subtle and gradual that patients sometimes ignore them or attribute them to the effects of aging. At first, patients may feel overly tired, "down in the dumps," or a little shaky. Their speech may become soft and they may become irritable for no reason. Movements may be stiff, unsteady, or unusually slow. Joe Dulaney says he was in "perfect health" nine years ago when his wife noticed that he had stopped swinging his right arm when he walked. Soon, simple tasks such as brushing his teeth and combing his hair became major ordeals. His right hand was always ice cold and he produced small, jerky letters when he wrote. Dulaney's doctor diagnosed the problem as arthritis and prescribed drugs to treat it. But symptoms worsened. Dulaney's voice dwindled to a slight whisper. Leg cramps, dry mouth, severe constipation, itchy eyes, and trouble turning over in bed tormented him. "My wrists were rigid and my fingers were not flexible, so I couldn't even button my shirt," he says. Still, another doctor seconded the arthritis diagnosis and prescribed different drugs. Finally fed up because his deteriorating condition prevented him from doing simple tasks such as turning newspaper pages, putting money in his wallet, and replacing a light bulb, Dulaney checked himself into a local hospital, arriving in such a weakened state he couldn't walk. Though a Parkinson's diagnosis rarely comes quickly, the three doctors who examined Dulaney at the hospital agreed within minutes that his classic symptoms indicated Parkinson's. The doctors gave him the Parkinson's drug levodopa, marketed as Larodopa and in generic forms, and the effect was nearly immediate. "In one hour or so I was walking the halls. I took a shower by myself and did one push-up to show off," says Dulaney. It was, for the moment, as if the disease had somehow vanished. But Dulaney says he soon became "fully aware" that because Parkinson's is progressive, he could manage some symptoms with drugs, but the disease wasn't about to go away. Treating the Disease The drug Dulaney took at the hospital, levodopa, is what doctors call the "gold standard" of Parkinson's therapy, because it is often the first-line treatment for the disease. Approved in 1970, levodopa helps restore muscle control when it is converted to dopamine in the brain. Why not give a patient dopamine directly? The reason is that dopamine cannot get through the body's blood-brain barrier, which screens out certain substances. But, although levodopa can pass through the barrier, it changes to dopamine so quickly only a small amount actually makes it into the brain. So to relieve symptoms, many patients need to take fairly large doses, which can cause side effects such as nausea and dyskinesias (involuntary movements). To reduce these drawbacks, doctors often
prescribe levodopa mixed with carbidopa, a drug that is marketed as Sinemet or in generic
versions. About 80 percent of Parkinson's patients take this drug, according to drug
industry estimates. Carbidopa delays the conversion of levodopa to dopamine until it
reaches the brain, often lessening or even preventing levodopa side effects. Carbidopa
also decreases the amount of levodopa needed. Because each Parkinson's patient reacts
differently to treatment, doctors and patients must work closely to find a tolerable
balance between the drug's benefits and side effects. Parkinson's experts are enthusiastic about the three new drugs FDA approved in 1997: Mirapex (pramipexole dihydrochloride), Requip (ropinirole hydrochloride), and Tasmar (tolcapone). Enrico Fazzini, M.D., who runs a neurology clinic in New York City, says the three new drugs are "really helping me to treat my Parkinson's patients more effectively." Mirapex and Requip, which mimic dopamine's role in the brain, allow patients to regain some of their lost muscle control. Both are approved for use alone or with levodopa drugs. In clinical trials, patients taking Mirapex alone saw as much as a 30 percent improvement in symptoms. Combining Mirapex with levodopa drugs allowed advanced patients to reduce those doses by up to 25 percent. Requip trials showed similar benefits, allowing patients to reduce levodopa doses by an average of 31 percent. Tasmar is a new kind of drug called a COMT inhibitor. It also is indicated for use with levodopa drugs. Researchers believe that Tasmar blocks a key enzyme responsible for breaking down levodopa before it reaches the brain. In trials, patients with a stable response to levodopa drugs who took Tasmar experienced significant improvements in daily activities such as talking, writing, walking, and dressing. "Although we are still looking for a cure, COMT inhibitors represent an entirely new class of therapy that will help many Parkinson's patients attain better symptom control," says Emilio Alonso-Mendoza, executive director of the National Parkinson Foundation. Parkinson's drug therapy also can include: A Brain "Pacemaker" FDA approved an important tool for controlling Parkinson's tremors last August. The Activa Tremor Control Therapy consists of a wire surgically implanted deep within the brain and connected to a pulse generator, similar to a cardiac pacemaker, implanted near the collarbone. Whenever a tremor begins, patients can activate the device by passing a hand-held magnet over the generator. The system delivers a mild electrical stimulation that blocks the dysfunctional brain signals that cause tremor. Effects are often dramatic. "Before the implant, patients can't raise a glass of water or a spoonful of food to their mouths without spilling it or striking themselves in the face," says William Koller, M.D., neurology chairman at Kansas University Medical Center. "Within hours, these same patients are sipping tea from a cup and eating peas with a fork, with no signs of their disability." Surgery Options A brain operation shown to be helpful for many
Parkinson's patients, especially those in late stages of the disease, is called
pallidotomy. Doctors are not sure why the procedure works, but an October 1997 report in
the New England Journal of Medicine stated that half of the patients in a pallidotomy
study at Toronto Hospital, who before the surgery needed help in eating, dressing, and
personal hygiene, were able to resume these activities independently. The study cautioned,
however, that some of the surgery's effects diminished after two years and that the
long-term effectiveness of the procedure still is unknown. For Tom Riess, who has undergone the procedure four times over the last six years, the surgery helped reduce his Parkinson's symptoms, especially the violent shaking, "which was literally killing me," he says. "Unfortunately, it left me with severely impaired speech, which is a fairly common consequence," says the 51-year-old Californian, a Parkinson's patient for 17 years. "Still, the tradeoff is worthwhile." Thalamotomy, a surgical procedure that destroys a specific group of cells in the thalamus, the brain's communications center, is aimed at the 5 to 10 percent of Parkinson's patients with disabling tremor in the hand or arm. It reduces or eliminates tremor in as many as 90 percent of patients. On the Horizon A number of potential Parkinson's treatments in
research laboratories now show much promise. They include: Experts say some of these new treatments are still far off. Others say they are hopeful that with bolstered research efforts, such as those earmarked in last year's Udall Act, innovative new therapies will be available in the near future. "I'm optimistic," says Perry Cohen,
52, a Washington, D.C., Parkinson's activist and patient for two years. "I think we
are on the verge of an important development. I'm confident that I won't have to go
through the agony I've seen others go through." For Parkinson's disease patients, both updated information and social interactions are key factors in battling the disease. Though patients seek these through traditional means such as their doctors, families and friends, many are turning to the Internet. Patients can compare notes on Parkinson's issues and stay in touch with others with the disease by subscribing to an Internet Parkinson's mailing list. Some of these lists deal with Parkinson's as one of a number of neurological disorders. Others focus on caregiving. One list that is an open forum just for Parkinson's patients is called "PARKINSN." Maintained at the University of Toronto, PARKINSN gives patients a place to pose questions or just let off some steam. A recent scan of the list revealed messages about exercises that can relieve some Parkinson's discomfort, surgery success stories, reviews of books about the disease, poems, even some Parkinson's jokes. One list member announced that he is marrying his doctor, and he invited everyone on the list to his wedding. To join PARKINSN, send an e-mail message to
LISTSERV@LISTSERV.UTORONTO.CA. In the body of the note, write: subscribe PARKINSN (your
first name) (your last name). Contact any of the following organizations to
learn more about Parkinson's disease and support groups: Parkinson's Institute Parkinson's Support Groups of America United Parkinson Foundation Source: John Henkel, FDA Consumer magazine (July-August 1998) |
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