GENE FOR PARKINSON'S
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
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
"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
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
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,
Parkinson's disease was first described in 1817 by the English
physician James Parkinson as the "shaking palsy". This common
chronic progressive disorder of late adult life manfiests as
tremors of the hands, muscular rigidity, slowness of movement
and a stooped posture and shuffling gait.
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
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
Related information on the
(3/95) Gene for Rare Parkinson's variant
AE (1/95) Brain Therapy for Parkinson's