University Times

In 1817, British physician James Parkinson published a paper describing what he called "the shaking palsy" and what later became known as Parkinson's disease — a slow-developing but irreversible degeneration of nerve cells in the part of the brain that controls muscle movements.

In the early 1960s, researchers finally identified the fundamental defect behind the disease: the loss of brain cells that produce dopamine, a chemical that transmits messages from one nerve cell to another within the brain. The discovery led to development of the drug Levodopa (or L-dopa), which enables nerve cells to produce dopamine and replenish the brain's dwindling supply. The researcher chiefly responsible for those 1960s advances — Oleh Hornykiewicz of the University of Vienna's Institute of Biochemical Pharmacology — will be one of the speakers at a free public symposium on June 14 to celebrate the establishment of the National Parkinson Foundation Center of Excellence at Pitt.

The symposium, scheduled for 2-5 p.m. in the Frick Fine Arts auditorium, will feature updates on the latest Parkinson's research and treatments, plus a historical overview by Hornykiewicz and a presentation on comparisons and contrasts between Parkinson's and Alzheimer's disease. See related story on this page.

A reception will follow the symposium.

Pitt's Parkinson center is the latest of 46 worldwide that the National Parkinson Foundation has designated as centers of excellence. That status entails a $50,000 annual grant and support services from the foundation. "But those things aren't really what's important," said center co-director Michael J. Zigmond, a Pitt professor of neuroscience.

"The designation itself is really the important thing," he said. "We've been found to be in the big leagues among Parkinson's research centers by a highly prestigious organization with a prestigious advisory board. I think this will be a major factor in our ability to raise money." Recently, the Pitt Program in Parkinson's Disease and Related Disorders received a five-year, $5 million grant from the National Institute for Neurological Disorders and Stroke, which more than doubled the group's annual funding.

But nationwide, Parkinson's research is underfunded, Zigmond said. The federal government spends $21 per victim on Parkinson's research, compared with $225 per victim for cancer research and $1,000 per victim for AIDS research, according to statistics published by the National Parkinson Foundation.

"The frustration, of course, is that the more funding there is [for Parkinson's research], the faster progress we can make," Zigmond said. Scientists know exactly what part of the brain is damaged by Parkinson's and they know more about dopamine than any other neurotransmitter, he noted.

"I have always claimed that the first neurological disease to be effectively treated and cured will be Parkinson's," he said.

Zigmond said a cure is probably 20-25 years away — "but that's a conservative estimate," he emphasized.

"New drugs are being developed even as we speak that will hopefully be more effective than L-dopa in treating symptoms and even reversing or stopping progression of the disease," Zigmond said.

Although L-dopa can stop the onset of debilitating symptoms — which include tremors, limb rigidity, stooped posture and slowness in movement — the drug does not stop the disease's progression. Also, it only works well for about 10 years and is effective only for three-fourths of Parkinson's patients.

Surgery also can alleviate Parkinson's symptoms. Eighteen months ago, surgeons at the University of Pittsburgh Medical Center (UPMC) began performing an improved version of a 1950s surgical procedure called pallidotomy. Surgeons use radiofrequency energy to destroy a small piece of a part of the brain called the pallidium; by interrupting a neural pathway, the procedure often relieves tremors and rigidity. UPMC has performed about 100 of the procedures in the last year and a half, Zigmond said.

Besides investigating new drugs, Pitt Parkinson's researchers are exploring gene therapy, among other possible treatments. "The idea behind gene therapy," Zigmond explained, "is to implant cells [into the brain] that are genetically engineered to produce dopamine." Progress in developing another promising therapy, transplantation of dopamine cells from aborted fetuses into the brains of Parkinson's patients, ground to a halt in this country in the early 1980s when the federal government ceased funding such research, Zigmond said.

Most Parkinson's victims are diagnosed with the debilitating disease after reaching their 50s. Most have had the disease for about 20 years before symptoms grow serious enough for them to seek help. "By the time the average patient is diagnosed with Parkinson's, 80 percent of the brain's capacity for producing dopamine has been lost," Zigmond said.

While many Parkinson's patients can live and work without developing debilitating symptoms for a decade or more, symptoms grow worse over time. Some victims end up unable to move or even swallow.

The disease is not contagious. Research has linked environmental factors such as exposure to certain heavy metals to Parkinson's, and it is thought that some people are genetically predisposed to the disease "although we don't know how yet," Zigmond said.

An estimated 500,000 to 1 million Americans suffer from Parkinson's, about 4,000 in the five-county area surrounding Pittsburgh. Tomorrow, June 13, at 1 p.m., Hornykiewicz will present a scientific seminar entitled, "Why Do the Nigro-Striatal Dopamine Neurons Die in Parkinson's Disease: The Question of the Primary Cause," in Auditorium 5, 4th floor, Scaife Hall.

— Bruce Steele