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Gene Therapy for Parkinson's Disease

22.06.2007
Injection of genetic information directly into the brain cells of patients (gene therapy) with neurodegenerative conditions such as Parkinson’s disease could safely alleviate symptoms of these conditions, conclude authors of a study published in this week’s edition of The Lancet.

However an accompanying comment questions the advantages of gene therapy over deep-brain stimulation, a current method for treating Parkinson’s disease.

Professor Matthew During, Weill Medical College of Cornell University, New York, USA, and colleagues did a safety and tolerability trial on 11 men and one woman, average age 58 years. The patients were divided into groups of four and given low, medium, or high dose, injections of the glutamic acid decarboxylase (GAD) gene, with associated adeno-associated virus (AAV). The injections were given into the subthalamic nucleus of the brain, and all took place at the Weill Medical College of Cornell University/New York Presbyterian Hospital, USA.

All patients survived the surgery and had no side effects related to gene therapy. Substantial improvements in movement were seen within three months of surgery in the side of the body opposite to that of the brain where injections were given, and continued until 12 months after surgery – the endpoint of the trial. Improvements in motor scores were also seen in both the “on” state (when subjects were on standard medication, and typically not improved with other surgical approaches), as well as the “off” state despite the gene therapy being given in only one hemisphere.

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Brain scans also showed reductions in metabolism in the ipsilateral thalamus (IT), similar to reductions which occur after other successful surgery for Parkinson’s disease. The study also showed a correlation between improved clinical motor scores and brain metabolism in the supplementary motor area, again similar to findings reported after surgery of patients with Parkinson’s disease.

The authors also point out that the gene therapy approach has advantages over the currently used deep-brain stimulation method. They say: “The absence of indwelling hardware [for gene therapy] reduces the risk of infection, and some patients with Parkinson’s disease simply prefer not to have the implanted device.” They add that frequent hospital visits would not be necessary for the gene therapy approach.

The authors conclude: “Our results show that AAV-mediated gene transfer can be done safely in the human brain, with no evidence of substantial toxic effects or adverse events in the perioperative period and for at least one year after treatment.”

In the accompanying Comment, Dr Jon Stoessl, Pacific Parkinson’s Research Centre, University of British Columbia, Canada, asks: “Apart from the avoidance of stimulator adjustments and potential hardware problems, what is the real advantage of this approach compared with deep-brain stimulation of the subthalmic nucleus?”

He concludes: “During and colleagues have taken a proactive approach to the treatment of neurodegenerative disease, and should be congratulated for their circumspection in the description of the potential implications of their findings. They made an important step in showing proof of principle, but much work should be done before neurologists and neuroscientists will regard this therapy as an effective approach.”

Tony Kirby | alfa
Further information:
http://www.thelancet.com/webfiles/images/clusters/thelancet/press_office/Parkinson's.pdf

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