Parkinson's Hope
 Brain scans of patients who received an experimental gene therapy for
Parkinson's disease provide proof that the therapy actually changes brain
circuits. As this ScienCentral News video reports, the first person to get
the treatment wants to give hope to others who suffer from the disease by
sharing his story.
Taking the Leap
"I couldn't live the way I was living. It was just too intense," says Nathan
Klein.
The married freelance television producer and father of two was 45 years old
when he found out that that his tremors and loss of motor control were
symptoms of Parkinson's disease. He tried various treatments and
medications, including dopamine drugs.
Explains Klein, "The symptoms don't get better. They get worse. And the
pills you take eventually don't help out. So, you know, what's there to look
forward to? Nothing."
So Klein researched experimental therapies and four years ago decided to
enroll in a clinical trial to assess the safety of an experimental gene
therapy for Parkinson's. He became the first person in the world to undergo
the procedure. Neurosurgeon Michael Kaplitt of Weill Cornell Medical Center
operated on Klein. He injected viruses carrying the therapeutic genes
directly into the overactive area of his brain, the subthalamic nucleus,
that controls movement. Because of the experimental nature of the study, the
twelve participants were only treated on one side of the brain. The study
was a joint endeavor with The Feinstein Institute for Medical Research
in Long Island.





Pioneering Technology





The patients reported an improvement in symptoms and none of them had side
effects from the procedure. In addition, Feinstein Institute neurologist
David Eidelberg and his team performed positron emission tomography (PET)
scans on the patients' brains before the surgery, and then again six and 12
months afterward. Eidelberg and colleagues pioneered the use of this
technology to identify networks in the brain. In this study, he monitored
two different networks, or circuits. One regulates movement and the other is
a thinking network. The scans measure activity or metabolism in these
networks.
"This is the first time that measuring a network has been used to assess the
outcome of a trial where you're looking to determine whether a therapy has
worked or not," explains Eidelberg.
Pedal to the Metal
"The gene therapy study was to look at an area of the brain called the
subthalamic nucleus. The area is overactive when you have Parkinson's
disease. So it represents a sort of a brake - a braking mechanism in a car.
And in normal people. when you want to stop moving it's depressed, and when
you want to move, the brake is relaxed a bit," says Eidelberg.
"Parkinson's - that's pedal to the metal; that brake is pushed all the way
down and the person can't move altogether."
The goal of the gene therapy is to relax that braking mechanism.
"Relaxing it just a tad, just a small degree, can help a person immensely in
terms of their capacity to initiate movement, plan movements and do simple
day-to-day activities," says Eidelberg.
"My life is a lot better now," says Klein. "I mean an incredible, incredible
transformation."

Scans show that treatment relaxed abnormally high brain activity.

The brain scan study confirms what Klein is feeling. Eidelberg explains that
the scans prove the overactive movement network actually changed. He wrote
in the Proceedings of the National Academy of Sciences that treatment
relaxed brain activity in the motor network, making a patient with severe
over-activity look like a person with moderate or mild Parkinson's disease.
And because patients only received the therapy on one side of their brains,
the researchers used the untreated side as a control.
"The network activity in the treated side went down while the other network
in fact got worse over the period of time. It was as if the disease had
progressed on one side of the brain, but not the other," says Eidelberg.
But just as important was to determine whether the gene therapy affected the
thinking network - and results show it did not.
"We also wanted to take this out of the realm of the subjective assessments
that are typically used in these kinds of circumstances and use modern
technology with computing, and just modern imaging to make that
determination independently. And this study was a big success, probably a
landmark from that standpoint," adds Eidelberg.

Eidelberg and his colleagues plan to start their next clinical trial in
early 2008. This will be a double-blind sham-operated placebo-controlled
phase II gene therapy study. If the therapy proves beneficial, the group
that received the placebo will be offered the therapy after the study ends.
Klein says that the medications that were ineffective before the operation
now help him when symptoms increase.
"It's really incredible," Klein says. "I mean, no one can understand unless
they had Parkinson's."
And, because he understands, he talks to others with the disease and offers
his comfort and support.
"There's hope-- that there are people in the field of curing the disease
that are becoming more successful in finding a cure," Klein says.
PUBLICATION: Proceedings of the National Academy of Sciences, November 19,
2007
TITLE: Modulation of metabolic brain networks after subthalamic gene therapy
for Parkinson's disease
AUTHORS: Andrew Feigin, Michael G. Kaplitt, Chengke Tang, Tanya Lin, Paul
Mattis, Vijay Dhawan, Matthew J. During, and David Eidelberg
RESEARCH FUNDING: Neurologix, Inc.

Rayilyn Brown
Board Member AZNPF
Arizona Chapter National Parkinson's Foundation
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