ANNOUNCER: Muhammed Ali has it. Actor Michael J. Fox has it. Like one million other Americans, they both suffer from Parkinson disease, a life long chronic disease that affects the motor system, the part of the brain that controls movement.
WILLIAM KOLLER, MD: We know that a small group of cells die in a very small part of the brain. It's called the substantia nigra, a black substance, and when those cells die, there's loss of a chemical, what we call a neurotransmitter, and that is dopamine, so the chemical basis of Parkinson is loss of this dopamine chemical in the brain. This has to do with our movements and how we coordinate our movements. So when that doesn't work, then we end up with slowness, stiffness and tremor.
ANNOUNCER: There are a variety of ways that science has tried to manage Parkinson disease.
WILLIAM KOLLER, MD: Charcot, a famous neurologist in France brought the first class of drugs, which are sometimes used even today, and they're called anticholinergics. This class of drugs has a lot of side effects, mental side effects, and are infrequently used.
ANNOUNCER: Other drugs have been used to slow or stop the enzyme activity that causes the breakdown of dopamine.
C. WARREN OLANOW, MD: The initial thinking was that we would block the metabolism of dopamine, make more dopamine available because we were blocking its metabolism.
ANNOUNCER: Researchers discovered a very effective way of increasing the supply of dopamine.
C. WARREN OLANOW, MD: Dopamine itself doesn't get into the brain, so they came up with the idea of using levodopa. Levodopa does get into the brain, and it is converted in the brain to dopamine and creates astonishing benefits in many patients.
ANNOUNCER: However early attempts with levodopa produced difficult side effects, such as nausea and vomiting. Another enzyme in the body was breaking down the levodopa, causing these side effects. Researchers solved the problem by slowing the action of the enzyme.
C. WARREN OLANOW, MD: To try and prevent that from occurring, levodopa is typically administered with an agent that blocks its conversion to dopamine in the blood. The agent that we use mostly in the United States is called carbidopa, and typically levodopa and carbidopa are administered together.
ANNOUNCER: During treatment, patient's may get the feeling that the medication is wearing off and their symptoms begin to return.
WILLIAM KOLLER, MD: Wearing off is a response to medicine where the duration of response of an individual dose gets less over time. And the terminology we use is like a light switch. When you turn it on, you're well controlled by the drug and you're free of symptoms. When you're in the off state, all the symptoms come back, the tremor, the slowness, the stiffness, the difficultly walking.
ANNOUNCER: Research soon discovered another enzyme was also contributing to levodopa's loss of effectiveness.
C. WARREN OLANOW, MD: It turns out that there is another enzyme, which is called COMT, and this COMT now degrades levodopa, thereby reducing the availability of levodopa to the brain.
When we block the COMT enzyme, it increases the half-life of levodopa by preventing its breakdown, and thereby extends its availability to the brain. So we have speculated that if you could give levodopa in combination with an agent that blocks COMT then you might be able to deliver the levodopa to the brain in a more continuous and more normal manner.
WILLIAM KOLLER, MD: There's a recent drug that's been released in the United States and throughout the world, and it's a combination of the carbidopa, levodopa, and what we referred to as the COMT-inhibitors. It's been placed in one pill. And the advantage of having it in one pill is that you get two drugs that inhibit the enzymes for levodopa. So the levodopa stays in the blood longer, and you get a much longer clinical response.
ANNOUNCER: Aside from the problem of treatments wearing off, the problem of medication side effects may occur. These can result in other motor problems.
C. WARREN OLANOW, MD: The other motor complication is dyskinesia. Here patients can experience wild, involuntary flinging movements that can themselves be a problem, and they cycle between these states throughout the day, experiencing inadequate periods of time in which they're just plain well controlled without dyskinesia.
Now, the recognition that patients suffer from these problems led to an attempt to develop other drugs that might provide benefit with a reduced risk of experiencing or inducing these problems. One class of drug that we use is called dopamine agonists.
What dopamine agonists do is they go directly to the brain, and they act directly on dopamine receptors to try and simulate the effect of dopamine.
WILLIAM KOLLER, MD: They have the advantage that they cause less long-term complications, such as wiggly movements and loss of an effect. Their disadvantages is they're not as good at controlling the symptoms as levodopa-containing compounds.
ANNOUNCER: Researchers continue to search for newer drugs with fewer side effects which will create longer-lasting relief from Parkinson's symptoms.
C. WARREN OLANOW, MD: The hope is that we'll eventually, or soon, preferably, develop a treatment that slows down or even stops the progression of the disease so that we can control the signs and symptoms and further levels of disability don't evolve. I think that's a realistic hope, and that we could potentially have such treatments within the next decade or two.