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Thursday October 26 7:10 PM ET
Gene Therapy May Affect Parkinson's

By PAUL RECER, AP Science Writer

WASHINGTON (AP) - A gene therapy experiment relieved
severe symptoms of Parkinson's disease in monkeys, and
experts say the technique offers promise for treating
the 1.2 million Americans who suffer from the disease.

A virus that had been joined with a gene that prompts
production of dopamine, a chemical neurotransmitter,
was injected into the brains of monkeys who had
chemically induced Parkinson's disease.

Three monkeys that had severe symptoms of Parkinson's
were restored to near normal by the gene therapy, said
Jeffrey H. Kordower, first author of a study appearing
Friday in the journal Science.

``We are able to stop the disease in its tracks and to
keep it from progressing,'' said Kordower, the
director of the Research Center for Brain Repair at
the Rush Presbyterian-St. Luke's Medical Center in
Chicago.

``The experiment showed dramatic protective effects,''
said Dr. Ted M. Dawson, head of the Parkinson's
Disease Research Center at Johns Hopkins University
Medical Center. ``It is promising, but I would be only
cautiously optimistic.''

Parkinson's disease, which affects about 1.2 million
Americans, is a progressive disorder that affects
brain cells that make dopamine. The loss of dopamine
causes the classic Parkinson's symptoms: trembling,
slow and stiff movement of limbs, a halting walk,
speech difficulties and loss of balance. Cause of the
disease is unknown and there is currently no cure.

Before the gene therapy could be tried in humans,
questions about safety would have to be answered,
Dawson said.

Dr. Mark H. Tuszynski, head of a brain disorder
research center at the University of California, San
Diego, said the experiment in monkeys was
``fascinating'' and offers the promise of ``a very
attractive therapy.''

He said, however, that it is not known whether the
brain cells affected by the chemically induced
Parkinson's in monkeys are precisely the same as those
affected by the actual disease in humans.

Kordower said a separate safety study is under way in
monkeys, and when that is completed in about six
months, an application for human clinical trials would
be prepared for presentation to the Food and Drug
Administration (news - web sites).

If all of the studies go smoothly, said Kordower, the
gene therapy could be ready for human testing in three
to five years.

In the experiment, researchers Patrick Aebischer and
Nicole Deglon at the Lausanne University Medical
School in Switzerland altered a virus so it carried a
human gene for a brain chemical called glial-derived
neurotrophic factor, or GDNF. This chemical prompts
the production of dopamine. The virus also was
modified so it would not cause an infection.

The altered virus was injected into the brains of aged
monkeys. Autopsies later showed the gene caused brain
cells to make dopamine and halted the normal
degeneration of brain cells.

In effect, said Kordower, the GDNF gene restored parts
of the aged brains to a ``youthful'' condition,
including an increase in the production of dopamine.

Kordower said the researchers then injected a group of
Rhesus monkeys with a drug, MPTP, that artificially
induces Parkinson's disease symptoms in both monkeys
and humans. Ten of the monkeys developed slow movement
and other symptoms of the disease.

Five of the monkeys were then given GDNF gene therapy
injections into the brain. Five others were given a
placebo. One monkey in each group died, for unknown
reasons, following the injections.

Of the four remaining monkeys in the gene therapy
group, three were totally relieved of the Parkinson's
symptoms. The four control monkeys continued to show
signs of the disease and became ``severely impaired,''
said Kordower.

He said the beneficial effect lasted for at least
eight months. The monkeys were then killed for a
detailed analysis of their brains.

In the treated monkeys, the analysis showed the
brain's dopamine production cells were protected and
there was an increase in levels of dopamine. Brain
cells in the control monkeys showed signs of
degeneration, he said.

Among the Americans with Parkinson's, only about 15
percent of the patients are diagnosed before the age
of 50. About one out of every 100 persons past the age
of 60 has the disease, experts say.

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YH

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