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Gene Therapy for Parkinsons Disease

According to the first scientific review of a dozen patients who have received the treatment over the last three years ,a novel gene therapy technique is safe and may be effective at staving off worsening symptoms of Parkinson's disease.

The patients, half of whom live on Long Island, are in advanced stages of the illness and were no longer responding to medicines when they signed on for the experimental therapy. The study was conducted by Andrew Feigin, MD, director of Neuroscience Experimental Therapeutics at The Feinstein Institute for Medical Research and his colleagues in collaboration with Parkinsons scientists at New York Presbyterian Hospital-Weill Cornell Medical Center in Manhattan.

One woman and 11 men received a surgical infusion of fluid containing a viral vector and genes for a protein called GAD, glutamic acid decarboxylase. This enzyme is critical in controlling a neurotransmitter called GABA. In Parkinsons, GABA is reduced in an area of the brain called the subthalamic nucleus.

This region is working on overdrive in the disease process and GABA is an inhibitory transmitter and is important in trying to calm this hyper-reactive circuit.

The gene therapy would be used to reduce symptoms and not alter the underlying disease process. Finding novel therapies are key as many Parkinsons patients stop develop complications after prolonged use of traditional medicines.

The Feinsteins David Eidelberg, MD, took brain scans before, during and after the treatment and the scans show that the brain is re-working these abnormal circuits. Dr. Feigin said that patients had about a 27 percent improvement in symptoms, although the study was an open label design.

The scientists are now designing a double-blind placebo controlled trial that would enroll far more patients in an attempt to see whether the gene therapy is effective in reducing symptoms.

The patients' scans showed a quieting of thes e areas, on the side of the brain where the genes were infused. The study was designed to inject the genes into one side of the brain. Normally, Parkinsons patients have worsening symptoms on one side of the body.

The novel strategy included packing genes that make an inhibitory chemical called GABA into pieces of viruses that have been rendered non-infectious. They began studying the experimental treatment in Parkinsons patients in 2003. Some patients continue to show improvement. Parkinson's patients have been willing to step up to the operating table for relief from the tremors, stiffness and rigidity that characterize the disease.

Decades ago, surgeons began to make lesions in parts of the brain involved in the disease, which lessened symptoms. Fetal stem cell surgery was pioneered in Parkinson's patients. And in the past decade, the deep brain stimulation has worked in as many as 70 percent of patients who have opted for the surgical procedure. If it doesn't work, the electrodes can be removed.

Gene therapy could be a more natural way to treat the disease, said Dr. Feigin. This important study shows that gene therapy can be performed safely and may benefits patients. The gene therapy technique was developed by Neurologix, a New Jersey-based company.

Parkinson's is a movement disorder caused by a progressive depletion of the brain chemical dopamine in the substantia nigra. These dopamine-containing cells control movement. When 70 to 80 percent of these cells are destroyed, a person develops the first symptoms of disease: tremors, slowed movement, muscle rigidity and problems with balance.

The main medication used in Parkinson's is L-dopa, which replaces dopamine in cells that are still working normally. Over time, the cell death is so massive that the effects of the medication disappear.


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