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Parkinson's studies back gene therapy

2 research teams report it's safe, eases symptoms

LOS ANGELES -- The first studies of human gene therapy for Parkinson's disease have shown that the technique is safe, and that it can reduce symptoms for patients, two groups of researchers have reported.

Each of the 24 patients who received therapy in the two separate trials received some benefit and none had significant side effects, researchers reported at neuroscience meetings yesterday and last week.

Gene therapy has a tarnished reputation because of problems encountered in trials against other diseases, said Katie Hood, deputy chief executive officer of the Michael J. Fox Foundation for Parkinson's Research.

The Food and Drug Administration temporarily halted gene therapy trials in 1999 after an 18-year-old being treated for a mild genetic disorder died after a violent reaction to the procedure. Trials were halted again in 2005 after three French children being treated for inherited immuno- deficiency disease developed leukemia and one of them died.

``It's very encouraging that two companies were able to show benefits with no significant adverse effects," Hood said. ``Safety is obviously the first hurdle."

Specialists and the researchers themselves, however, cautioned patients against investing too much hope in the findings because Parkinson's studies are notorious for showing placebo effects.

Only when the techniques are tested in controlled trials, now in the planning stages, will researchers be able to determine whether the benefits are real, and if they are long-lasting.

Parkinson's, which strikes as many as 100,000 Americans each year, is characterized by severe tremors and rigidity in the limbs and loss of muscle control. Although its cause is unknown, the disorder results from the death of brain cells that produce a neurotransmitter called dopamine, which plays a key role in transmitting commands from the brain's muscle-control centers.

The two teams used the same technology for performing gene therapy, inserting a desired gene into a common virus called adeno-associated virus.

While that virus readily infects humans, it has never been shown to cause disease. But the genes they used were quite different.

One team, led by Dr. Matthew J. During of the Weill Cornell Medical Center in New York, used a gene that is the blueprint for an enzyme called glutamic acid decarboxylase. That enzyme converts chemicals in the cell into a neurotransmitter called GABA, which is essential for controlling muscle movements.

Earlier studies in animals and humans show that Parkinson's disease is marked by a deficiency of GABA in a part of the brain called the subthalamic nucleus.

Injecting GABA directly into the brain can ease symptoms of the disease, but the hormone is quickly cleared, limiting its benefits.

During's team injected one side of the brain of 12 patients with one of three different concentrations of the gene therapy agent.

He said at an Atlanta meeting of the Society for Neuroscience yesterday that all 12 patients had an improvement of at least 25 percent on a conventional scoring system used to assess the severity of Parkinson's symptoms, nine had an improvement of at least 37 percent, and five had an improvement between 40 percent and 65 percent.

The benefits have persisted for a year. Most benefits from a placebo effect, researchers noted, are transient.

Sophisticated imaging of the patients' brains showed an increase in metabolism on the side where gene therapy was performed, and the amount of increase correlated with the degree of improvement in symptoms, During said.

The gene therapy agent was made by Neurologix Inc. of Fort Lee, N.J., a company created by During and his colleagues to commercialize the technology.

Neurologix funded the study. During said that the neurologists who assessed the patients' condition had no financial ties to the company.

The second study, led by Dr. William J. Marks Jr. of the University of California at San Francisco, used the gene for a growth factor called neurturin that is closely related to the better-known growth factor GDNF.

Studies in animals and in humans have shown that injecting GDNF into the a section of the brain known as the putamen can impede, and possibly reverse, the loss of dopamine-secreting cells.

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