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Gene Therapy Shows Promise for Parkinson's
Date:10/14/2009

Treatment tested in monkeys addresses only motor issues, though, experts say,,,,

WEDNESDAY, Oct. 14 (HealthDay News) -- Macaque monkeys that received gene therapy for symptoms of Parkinson's disease saw a significant improvement in their motor function without the side effects associated with current standard therapy, researchers say.

Simultaneous insertion of three genes allowed certain cells in the brain to take over production of the neurotransmitter dopamine. Too-low levels of dopamine cause the hallmark motor-control symptoms of Parkinson's.

But even if this gene therapy approach were to someday produce good results in humans, it still would not solve many of the myriad other problems associated with Parkinson's.

Although tremors and other movement problems mediated by dopamine are characteristics of Parkinson's, people with the disease are also likely to develop dementia, behavior problems, depression, anxiety, heart problems, loss of the ability to smell, constipation and sexual dysfunction, most of which are not related to dopamine, said Dr. Fatta Nahab, assistant professor of neurology and director of movement disorder research at the University of Miami Miller School of Medicine.

"The studies that are being done are addressing the dopamine problem in Parkinson's and treating some of the movement-related symptoms," Nahab said. "That doesn't necessarily fix any of the other non-movement-related symptoms of Parkinson's, which can actually cause a greater amount of disability."

Dr. Bechir Jarraya, from the department of neurosurgery at Henri-Mondor Hospital in Paris and the study's lead author, said that the gene therapy would be considered a treatment rather than a cure because it "corrects only dopamine-related symptoms."

For the past 40 or so years, the treatment of choice for Parkinson's has been so-called dopamine replacement therapy, which uses drugs to increase dopamine levels in the brain.

The approach helps, but because the infusion of dopamine takes place in fits and bursts, not continuously, people often develop involuntary movements.

Scientists have thus been focused on finding ways to deliver dopamine to the brain more continuously.

The new study, published Oct. 14 in Science Translational Medicine, represents one such effort.

After inducing Parkinson's-like symptoms, such as tremors and rigidity, in macaque monkeys, French researchers inserted three genes involving dopamine production. The genes had been introduced into animals before, but separately, never with the same viral delivery system, according to the study.

Dopamine was restored and sustained at about 50 percent of normal concentrations, resulting in motor improvements without the side effects seen with conventional drugs, the study found. The benefits were seen for up to 44 months.

But the genes were introduced into nerve cells that normally do not produce dopamine, which could foreshadow problems.

"They were basically giving non-dopamine cells the machinery to produce dopamine on their own, completely unrestricted," Nahab said. "That's a little bit different from prior studies, which have tried to use a drug that would convert to dopamine. In this case, there are some additional safety concerns."

Jarraya, however, pointed out that "in monkeys, [the therapy] has proved 'safe' even after 44 months, which was the longest follow-up."

When the therapy might be ready for use in people, however, remains unclear.

"What they've done, and the success they've had is very exciting and very promising, but I wouldn't basically say the next step is doing this in humans," Nahab said. "It's a small study. I think we're going to need more, larger trials in non-human primates to assess for safety."

The French researchers, though, said that an early-phase clinical trial in humans is in progress. "So far, six Parkinson's disease patients have been treated -- no serious adverse events, encouraging results so far," Jarraya said. "[But] the study is not ended, so still no final results."

Roughly 50,000 Americans are diagnosed with Parkinson's disease each year, according to the U.S. National Institute of Neurological Disorders and Stroke. The average age of onset is 60.

More information

The U.S. National Institute of Neurological Disorders and Stroke has more on Parkinson's disease.



SOURCES: Fatta Nahab, M.D., assistant professor, neurology, and director, movement disorder research, University of Miami Miller School Medicine, Miami; Bechir Jarraya, M.D., Ph.D., Department of Neurosurgery, Henri-Mondor Hospital, Paris, and head, cognitive and translation neuroscience laboratory, Inserm (National Institute of Health and Medical Research), Paris; Oct. 14, 2009, Science Translational Medicine Medicine


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