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The Parkinson's Problem

Many people associate Parkinson's disease with the celebrities who visibly suffer from it, from Michael J. Fox to Pope John Paul II. One reason we can often identify people with Parkinson's disease is because they have the signature symptom: a noticeable tremor. As a motor system disorder, Parkinson's disease also causes muscle rigidity, shuffling gait, and impaired balance and coordination.

It's difficult to know who is at risk for Parkinson's disease, though age appears to be the strongest predictor. Other risk factors include a first-degree relative with the disease; exposure to certain pesticides and herbicides; and the overuse of certain medication such as the anti-psychotic Haldol.

Medications for Parkinson's disease can control symptoms by stimulating or replacing the brain chemical dopamine. But the most effective medications, called levodopa-containing compounds, tend to "wear off," so each dose does not last as long as it once did. Doctors sometimes hold off on starting these medications in an effort to delay the wearing-off effect. And new combination therapies help provide relief from symptoms for a longer period of time.

Below, William Koller, MD, PhD, founder of the University of Kansas Parkinson Disease and Movement Disorder Center in Kansas City, discusses the most common treatments for Parkinson's disease.

What is Parkinson's disease?

Parkinson's disease involves symptoms including slowness of movement, stiffness of the muscles, difficultly walking, tremor (which some people refer to as shakiness) and sometimes difficulty with balance.

What causes Parkinson's disease?

We have a fairly good knowledge of what happens in the brain in Parkinson's disease. We know that a small group of cells die in a very small part of the brain. When those cells die, there's a loss of dopamine, which is a brain chemical or what we call a neurotransmitter. So the chemical basis of Parkinson's is loss of this dopamine chemical in the brain.

The part of the brain that's involved in Parkinson's is called the basal ganglia, and it helps control our movements and how we coordinate them. So when the basal ganglia doesn't work, we end up with slowness, stiffness and tremor.

How common is Parkinson's disease?

Parkinson's disease can affect all individuals and may be slightly more prominent in men. It's estimated that, at least in the United States, there's probably one million people affected with Parkinson's disease. Once you get over age 65, 1 percent (that is, 1 in 10) of people are at risk for Parkinson's disease. About 10 percent of cases occur before age 50, which we call young-onset Parkinson's disease, and of course, Michael J. Fox would be an example of someone with young-onset Parkinson's disease.

How can we predict who will get Parkinson's disease?

Currently, we can't predict who will get Parkinson's disease. In a very small group of individuals, maybe 1 percent of people with Parkinson's disease, it runs in the family; some of these genes have been identified. Age itself is a risk factor; the older you get, the more likely you're going to develop Parkinson's disease. But there's no test we can do at this point and say, "Yes, you're going to develop Parkinson's disease."

How does Parkinson's disease affect the quality of people's lives?

Parkinson's disease can be a very disabling condition for some individuals. In addition to its motor symptoms such as slowness, stiffness and shakiness, Parkinson's also involves other symptoms: you can have depression, constipation, sexual dysfunction and sleep abnormalities. All these symptoms can significantly reduce quality of life in some patients.

How is Parkinson's disease treated?

There are a number of medical and surgical treatments for Parkinson's disease. Historically, Charcot, a famous neurologist in France, introduced the first class of drugs, which are sometimes used even today, and they're call anticholinergics. This class of drugs has a lot of side effects, however, and is infrequently used.

Today, there are two main classes of drugs to treat Parkinson's disease: levodopa-containing compounds and a group of drugs called dopamine agonists.

How do the levodopa-containing compounds work?

The gold standard for treatment of Parkinson's disease is levodopa-containing compounds, along with the drug Sinemet (carbidopa). It's based on an amazingly simple concept. You don't have enough dopamine in the brain, so we give the chemical L-Dopa, which goes into the brain and is converted to dopamine. We replace the deficiency, and the symptoms get dramatically better.

What happens, however, though, is that people sometimes develop wiggly movements, which we call dyskinesias and the benefit from an individual dose gets less over time. So, for instance, if one pill gave you four hours of benefit at, say, year three of the disease, by year 10 of the disease, the same pill may now only give you two hours of benefit. So it always works, but the duration of benefit from an individual dose gets less and less over time.

Are there ways of getting the levodopa to last longer?

One of the main problems with the long-term use of levodopa is that its duration of effectiveness gets shorter and shorter over time. So there's been a lot of emphasis in making its duration of effect longer. The L-Dopa is metabolized by two enzymes in the body. One is called carbidopa, and the second enzyme is called COMT. And we now have inhibitors or blockers of that enzyme. When you block that enzyme, the blood level of levodopa is much extended in the patient. When you extend the blood level, you also extend the duration of the clinical response.

These drugs are called COMT inhibitors, and they've been very useful in the motor fluctuations and extending the duration of effect. You can imagine, if you are "off"?which in our terminology means the drug's not working?three to four hours a day and you're shaking and you're slow, you can't do the things you need to do. But with these drugs, sometimes the "off" time goes away, so the drug's working through the whole day, and that's of course, our goal in the treatment of Parkinson's disease.

How do the dopamine agonists work?

The dopamine agonists are a class of drugs that directly stimulate the dopamine receptor, so they make up for the dopamine deficiency in Parkinson's. They cause fewer long-term complications than levodopa-containing compounds such as the wearing-off problem. Their disadvantage is that they're not as good at controlling the symptoms as levodopa-containing compounds.

If you look at control of symptoms, in early disease, dopamine agonists and levodopa are somewhat equal. As the disease advances, however, levodopa-containing compounds are much more effective.

What is the current medication strategy for younger people with Parkinson's disease?

We use dopamine agonists in the young-onset patients, and the reason it's probably more important in them is that these patients are more likely to develop the levodopa-induced dyskinesia and the wearing-off problem. If you're 40 years old, you probably have 30 or 40 year's worth of life left, so you have a lot of time to develop these potential complications. So, with patients in their 40s or 50s, the common practice among neurologists now is to start the dopamine agonists first and save levodopa for later.

Posted by thinkum at April 29, 2004 01:22 PM