By Sean Henahan, Access Excellence

Bethesda, MD (Nov. 14, 1996) The discovery of a gene associated with Parkinson's disease provides an important new avenue of research into the cause and potential treatment of the debilitating neurological ailment.

Image: SPECT scan transaxial brain series showing Parkinson's disease dementia (Harvard).

By analyzing the DNA of patients with a rare familial form of the disease, a team of researchers were able to narrow the search for a specific gene on chromosome four that, when altered, appears capable of causing the disease.

"This exciting result gives us a powerful new tool to understand why nerve cells die in Parkinson's disease and how to stop them from dying. It will usher in a new era of Parkinson's disease research," says National Institute of Neurological Disorders and Stroke Director Zach Hall, Ph.D.

The researchers identified the gene region by studying the DNA of 28 members of a large Italian family containing almost 600 people. People in this family, some of whom migrated to the United States between 1890 and 1920, can trace their ancestry to a single couple who lived in Italy in the 18th century. More than 60 family members on both sides of the Atlantic have been diagnosed with Parkinson's disease.

"We don't know that this gene affects all people with Parkinson's disease, since we've only found it in one family. But this is a very important step. We now know what we have to do to understand what causes the disease," noted Roger Duvoisin, M.D., of UMDNJ-Robert Wood Johnson Medical School.

Having narrowed the search to a specific region of chromosome 4, the next step will be to locate and characterize the specific gene involved. This in turn could lead to genetic testing that will help early diagnosis and treatment. New treatments for Parkinson's disease could also be developed based on the new genetic information.

"Mutations in the gene located in this region will cause classical Parkinson's disease, the very same symptoms commonly found in most people with Parkinson's. Understanding how that happens will help fit all the pieces of this complicated disease together," notes study director Mihael Polymeropoulos, Ph.D., National Center for Human Genome Research.

"Information on inheritance patterns of the disease opened the door to an aggressive approach to understanding the genetics using the gene-finding tools of the Human Genome Project," says Polymeropoulos. "Once we started studying DNA from the families, we were able to map the gene in a matter of weeks. Past disease-gene hunts have taken anywhere from years to decades."

The findings are reported in the November 15, 1996 issue of Science . The research team included members from the National Institutes of Health (NIH), the National Institute of Neurological Disorders and Stroke, the UMDNJ-Robert Wood Johnson Medical School in New Brunswick, New Jersey, and the Istituto de Scienze Neurologiche in Naples, Italy.

BACKGROUND

About 50,000 Americans are diagnosed with the disease each year. This is a mysterious disease with no known cause or cure. The cause of Parkinson's disease is currently thought to be a combination of environmental and genetic factors.

The first treatment breakthrough came with levadopa. The drug essentially replaces the lost dopamine in the brain. However, large doses are required, resulting in undesirable side effects, such as nausea, heart problems & dementia. The subsequent development of carbidopa, which is given in conjunction with levadopa, allows a smaller dose of levadopa to be used, resulting in fewer side effects.

Many patients respond well at first to this combination therapy, but after a couple years of treatment the effects may begin to wear off. At the same time, prolonged use of levadopa can have serious side effects including involuntary movements of the limbs and psychological disturbances.

A new treatment called seligiline has recently become available which has a completely different mechanism of action from levadopa. The drug is potent inhibitor of an enzyme called 'monoamine oxidase B' which breaks down dopamine. This means more dopamine can be preserved in the brain. The drug appears to have a neuroprotective effect and may delay the onset of Parkinson's symptoms.