Drugs Helping People with Parkinson's Disease

by Food and Drug Administration (FDA)

Walter is approaching 80, but his smooth, unlined face looks years younger. When he sits quietly in his chair, no one can tell he has Parkinson's disease. He has never had tremor, the trembling of the hand or foot that plagues the majority of people with this chronic neurological ailment.

But watch him try to get out of the chair. He grips the wooden arms, moves to the edge of the seat, and rocks back and forth a number of times to gain momentum. Using all his strength, he pushes down on his hands to propel himself upright. For a long time he stands as if rooted to the spot. Then he hurries forward, shoulders bent, walking in short, shuffling steps, looking every one of his 80 years.

For the most part, Walter (who asked that his last name not be used) has coped remarkably well with his illness, which began when he was 65. Until a few months ago, he drove his car around the rural area where he lives, doing his little errands. But lately he appears to be going downhill rapidly despite carefully regulated medication. Doing fine tasks with his hands, such as buttoning his shirt and handling eating utensils, has become more and more difficult, which depresses him. Slight drooling has also become a problem. But what bothers him most is that he has begun to hallucinate, a side effect of one of the drugs he is taking. He stands at the window and peers into the woods, seeing strange creatures that are not there, but appear only too real to him. His daughter reports that this retired policeman, once strong and confident, becomes anxious when left alone. Since it's not possible for her to be with him all the time, she is thinking, finally, of a nursing home.

Unlike Walter, Virginia "Jinny" Krohnfeldt's first symptom was a tremor that affected her writing hand. Her symptoms showed up much earlier, too, when she was in her mid-40s, 13 years ago. Presently a realtor in the Washington, D.C., area, Krohnfeldt had to resign her high level government job because it became difficult for her to sign checks, an essential part of her duties. Like Walter, Krohnfeldt also stoops and shuffles, symptoms that make her appear to many people as if she is a drug abuser. Once reluctant to tell people she had Parkinson's disease, Krohnfeldt is now outspoken about her condition: "Better to say you have Parkinson's than have people think you're on drugs."

Diagnosing the Disease

The chief or major signs of Parkinson's disease are slowness of movement (bradykinesia), tremor, and muscle stiffness or rigidity.

In addition to these, Parkinson patients may have minor signs, including a mask-like face (which accounts for Walter's deceptively youthful look), drooling, stooped posture, "freezing" (feet unable to move), difficulty swallowing, mumbly speech, sleep disturbances, a tendency to fall forward (propulsion) or backward (retropulsion), infrequent blinking, and bowel and bladder problems. Diagnosis is based on the presence of two major signs, or one major sign and at least two minor signs. Often, the disease progresses so slowly that it may take years before a doctor can make a firm diagnosis.

To rule out other brain disorders, doctors may also order tests, such as a computerized axial tomography ("CAT") scan, which produces images of "slices" of the brain, or an electroencephalogram (EEG), which measures electrical activity in the brain. These tests are usually normal in patients with Parkinson's disease.

Dopamine Key

Parkinson's disease results from a depletion of the chemical dopamine in the brain. Dopamine is produced and stored in a small, pigmented group of nerve cells in the upper brainstem called the substantia nigra. Long, thin fibers connect these pigmented cells to nerve cells in the corpus striatum, a part of the brain that controls movement, balance, walking, and posture. Dopamine aids the transmission of messages between the pigmented nerve cells and the striatal nerve cells.

If, for any reason, the substantia nigra's nerve cells are injured or destroyed, the corpus striatum does not receive enough dopamine to correctly program movement, and parkinsonian symptoms develop. Symptoms may not show up until more than 50 percent of the dark nerve cells are destroyed and the striatal dopamine content is reduced by 80 percent or more, a process that can take many years. During the course of the disease, the substantia nigra continues to degenerate.

Treatment with Levodopa

In 1817, the British physician James Parkinson described as the "shaking palsy" the disease that now bears his name. He had little at his disposal to relieve the disease's disturbing symptoms. Medical men of his time were great believers in keeping the bowels open and bloodletting; Dr. Parkinson approved of the former for palsy patients, but not the latter.

Until levodopa (or L-DOPA) was introduced in the 1960s, doctors relied mostly on botanical preparations, such as tincture of belladonna, to treat the disease. Then Arvid Carlsson, a Swedish professor, found in 1957 that the effects of reserpine, a drug that caused parkinsonism in laboratory animals, could be reversed by injections of levodopa. He proved that dopamine levels in the brain were reduced by reserpine and restored to normal by levodopa, and suggested that levodopa be tried in treating Parkinson's disease.

Doctors prescribed the drug timidly at first — either given by mouth or injected into a vein — fearing serious adverse reactions. The results were disappointing. But George Cotzias, M.D., of the Brookhaven National Laboratories, Upton, N.Y., daringly prescribed doses a thousand times greater than had ever been used. His patients improved dramatically. When Leonard L., a postencephalitic Parkinson patient (and hero of the movie "Awakenings," based on the book by Oliver Sacks, M.D.), heard about the drug, he spelled out on his letterboard, "Dopamine is Resurrectamine. Cotzias is the Chemical Messiah."

FDA approved levodopa in 1970. But there were problems. Curiously, levodopa can cross the blood-brain barrier — where it is converted in the brain to dopamine — but dopamine itself cannot. When taken orally, an enzyme in the blood and tissues converts levodopa to dopamine so rapidly that only a small part of a levodopa dose enters the brain unchanged. Consequently, large amounts of levodopa are needed to relieve neurological symptoms and replace the lost dopamine, causing unbearable nausea and other side effects.

About the Author

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