LISTSERV 16.0 - PARKINSN Archives

The following news is not only great news in its own right but adds
to our point that neuroscientists are close to finding a cure for
Parkinson's. So lets spend the measly $100 million a year provided
for by the Udall Bill and realize the vision of a world without
Parkinson's. WE ARE GOING TO POUND ON THE DOOR THIS
YEAR UNTIL THEY OPEN IT AND AGREE TO PROVIDE MORE FUNDING.
This news that we are one step closer just strengthens my resolve,
and as many of you know my resolve was pretty strong already.

Bethesda, MD - For the first time, scientists have pinpointed the location of a gene they
believe is responsible for some cases of Parkinson's disease. Their discovery provides
strong evidence that a genetic alteration is capable of causing the disease. The study,
published in the November 15 issue of Science,1 sheds light on the mysterious origins of
this devastating neurological disease that affects at least 500,000 Americans.

The findings are reported by National Institutes of Health (NIH) scientists from the
National Center for Human Genome Research (NCHGR) and the National Institute of
Neurological Disorders and Stroke (NINDS), in collaboration with researchers from the
UMDNJ-Robert Wood Johnson Medical School in New Brunswick, New Jersey, and
the Istituto de Scienze Neurologiche in Naples, Italy.

"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 NINDS Director Zach Hall, Ph.D.

Efforts to locate the gene intensified after an August 1995 NIH-sponsored workshop on
Parkinson's disease at which scientists from NCHGR and NINDS met Roger Duvoisin,
M.D., of UMDNJ-Robert Wood Johnson Medical School. Soon after, the NIH scientists,
led by Mihael Polymeropoulos, M.D., of NCHGR, began to carry out a genetic
analysis of Parkinson's disease using DNA from patients identified and followed by an
international team led by Dr. Duvoisin.

The impact of the current finding is to show that a single gene alteration can cause the
disease. The next step will be to find and identify the specific gene involved, which is
located somewhere within a region of DNA on the long arm of chromosome 4. Learning
the gene's exact location and isolating it may eventually lead to genetic testing that will
help early diagnosis and treatment. Learning what the gene is and how it works may
help researchers design treatments for all forms of Parkinson's disease--not only
inherited cases, but also those with no familial link

"We don't know that this gene affects all people with Parkinson's disease, since we've
only found it in one family," says Dr. Duvoisin. "But this is a very important step. We
now know what we have to do to understand what causes the disease."

Until recently, most scientists believed the disease was due almost exclusively to
environmental factors such as drugs or toxic chemicals, although in most cases, no
environmental cause has been identified. But many people appear to have an inherited
susceptibility to the disease. Studying a causative gene will help researchers discover
how the disease occurs and how to develop methods of preventing or curing the disease.

"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," says Dr.
Polymeropoulos, lead author of the report. "Understanding how that happens will help
fit all the pieces of this complicated disease together."

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.

Dr. Duvoisin and his colleagues have studied the inheritance patterns of Parkinson's
disease for decades. In the 1980's, they began studying families with multiple cases of
the disease. They have now defined the pattern of inheritance in 80 multicase families.

"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 Dr. 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 gene mutation in this family is inherited in a dominant fashion, meaning that
people who possess the mutation have a 50 percent chance of passing it on to their
children. Only one parent must carry the mutation for the disease to appear in a couple's
offspring. The symptoms of familial Parkinson's are identical to those in families with
no history of the disease, except that the inherited form sometimes develops earlier in
life.

Symptoms of Parkinson's disease include tremor (particularly tremor of a body part at
rest), stiff limbs, slow or absent movement, lack of facial expression, a shuffling gait,
and a distinctive stoop. Other symptoms, such as depression and impaired ability to
think may also develop, especially during the later stages of the disease. These
symptoms result from degeneration of nerve cells in the brain. The withered cells fail to
release dopamine, one of the neurotransmitters, or nerve signaling chemicals, crucial for
communication between nerve cells.

To learn what percentage of Parkinson's disease patients possess an alteration in the
chromosome 4 gene, Dr. Polymeropoulos and his colleagues plan to study additional
families with several affected individuals to see if they carry the distinctive marker in
the same region on chromosome 4. Although many families have more than one
member with Parkinson's disease, "there are not very many of the size of the family that
we used, so it may be a question that will take some time to answer," says Dr.
Polymeropoulos. Families with different inheritance patterns may have mutations that
are different from the one found in the Italian family.

"Even with a relatively common disease like Parkinson's, it is rare to find families or
situations that give us such particular insight and research power," says Robert
Nussbaum, M.D., Chief of NCHGR's Laboratory of Genetic Disease Research. "We
need the help of the public, as well as physicians who are out there taking care of those
patients, to keep their eyes open for these unusual situations which can be so helpful in
furthering our research."

The long list of people with Parkinson's disease includes evangelist Billy Graham,
science journalist Earl Ubell, and Attorney General Janet Reno. Many other people,
including the former boxer Muhammed Ali, have Parkinson's-like symptoms due to
head injury, toxic chemicals, or other problems. Another Parkinson's-like disorder,
Wilhelmsen-Lynch disease (disinhibition-dementia-parkinsonian-amyotrophy complex),
has been linked to a region of chromosome 17. A defect in mitochondrial DNA, which is
separate from a person's chromosomes, was recently linked to sporadic Parkinson's
disease with unusual symptoms. Other genetic mutations may also play a role in some
cases.

The NCHGR oversees NIH's role in the Human Genome Project, an international
research effort to develop tools for gene discovery. The NINDS is the nation's leading
supporter of research on the brain and nervous system and a lead agency for the
Congressionally-designated Decade of the Brain.