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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 [log in to unmask] ---------------------------------------------------------------------- To sign-off Parkinsn send a message to: mailto:[log in to unmask] In the body of the message put: signoff parkinsn