University of Virginia Researchers Make Cellular Model of Parkinson's Disease

CHARLOTTESVILLE, Va., Feb. 12 (AScribe Newswire) -- For the first time, scientists at the University of Virginia Health
System have engineered cells that produce the pathological hallmark found in the brain cells of all patients with
Parkinson's disease - Lewy bodies, tiny balls of damaged protein, found only in the brain and discovered more than
ninety years ago.

The U.Va. research on Lewy bodies means that scientists now have a model of the pathological changes found in
Parkinson's disease "in a dish" and can use this cellular model for experiments that may show promise in treating or
reversing the effects of Parkinson's. The research is published in the February 2004 issue of the Journal of
Neurochemistry, which can be accessed on the web at: http://www.jneurochem.org/current.shtml

"The best way we can study Parkinson's is through a model that replicates the pathological features of the disease,"
said Patricia Trimmer, lead author of the study and associate professor of research at U.Va.'s Department of Neurology.
"Previously, the only way we could study Lewy bodies was in brain samples from patients with advanced Parkinson's
disease who had died. This cell culture system provides us with a living pathological model, a new tool."

Symptoms of Parkinson's disease include tremors, rigidity, slowing of movement and difficulty with posture and balance.
The disease is caused by the degeneration of nerve cells in a part of the brain, called the substantia nigra,
responsible for the production of dopamine, which is essential for nerve cells to function. Up to one million Americans
suffer from Parkinson's and incidence increases with age, according to the Parkinson's Disease Foundation. There is no
cure for the disease, but there are treatment options such as surgery and medication to manage the symptoms.

So far, little is known about the development and function of Lewy bodies. With this new model, researchers and
clinicians at U.Va. now can study how Lewy bodies form to determine if they are good or bad for the cell. "Clearly
something has happened in the cell for Lewy bodies to develop, we just don't know what," Trimmer said. "So the question
becomes, how can we stop Lewy bodies from forming? Or if Lewy bodies are good, how do we keep them growing? If I stress
the cell with free radicals will it make Lewy bodies? Can I interfere with how Lewy bodies are being made? We here at
U.Va. are designing experiments now to answer those and many other questions."

Trimmer and her colleagues at U.Va.'s neurology department worked for more than five years to characterize this
cellular hybrid or "cybrid" model of the pathology of a Parkinson's brain cell. Using a process developed by U.Va.
neurologist Dr. W. Davis Parker, Jr., Trimmer and her colleagues treated a human cell line (neuroblastoma) with a
chemical that destroyed the DNA found in the cell's mitochondria, the cellular "power house" responsible for energy
production. Previous research at U.Va., published in the Feb. 1997 issue of the Annals of Neurology, found that
Parkinson's could be passed on by the mother through mutations of mitochondrial DNA. U.Va. researchers found a
preponderance of maternal inheritance in families where a Parkinson's patient has both an affected parent and sibling.

Mitochondrial DNA derived from platelets donated by Parkinson's disease patients was inserted into these human
neuroblastoma cells. To Trimmer's surprise, Lewy bodies appeared under the microscope several months later. "The only
thing we put in these neuroblastoma cells that persists is the mitoDNA and whatever proteins they encode," Trimmer
said. "Something is clearly disturbing the cellular functions so badly that the cell manufactures Lewy bodies and this
happens just because we inserted the mitoDNA from a Parkinson's patient."

"This work by Pat Trimmer and her colleagues establishes that the cybrid model of Parkinson's is the most valid model
of sporadic Parkinson's available today," said Dr. James Bennett, professor of neurology at U.Va. and Director of the
Center for the Study of Neurodegenerative Diseases. "The Lewy bodies arose spontaneously and are such perfect replicas
of what is found it the brain."

Much published research on Parkinson's involves the study of genes responsible for rare forms of the disease. But the
work by the U.Va. team resulted in a model that produces Lewy bodies in sporadic Parkinson's that afflicts 98 percent
or more of Parkinson's patients, according to Bennett. "Our work shows that mitochondrial DNA is altered in Parkinson's
and can recreate the disease pathology inside cells," he said.

The study was funded by a grant from the National Institute of Neurological Disorders and Stroke.

Media Contact: Bob Beard, U.Va. Health System Media Relations, 434-982-4490

SOURCE: AScribe Newswire
http://tinyurl.com/2ayyu

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