Treating Parkinson's Diseas, A Brain Pacemaker

by Food and Drug Administration (FDA)

(Page 2 of 3)

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.

Though the levodopa-carbidopa combination can be so effective that some patients forget for a while that they have Parkinson's, the drug is far from perfect. Side effects aside, doses typically must be increased over time, and the disease often manifests an "on-off" syndrome in advanced patients in which the drug simply doesn't work for unpredictable durations. Fortunately, alternatives are available.

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:

Parlodel (bromocriptine) and Permax (pergolide), which mimic dopamine's role in the brain. They are sometimes given with levodopa drugs to improve response.

Eldepryl (selegiline hydrochloride), also called deprenyl and available in generic versions, which can enhance and prolong levodopa response by delaying the breakdown of naturally occurring and levodopa-formed dopamine, allowing accumulation in surviving nerve cells.

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."

About the Author

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