Neurology, diagnostic imaging

Brain scans show gene therapy normalizes brain function in Parkinson's patients

26 November 2007

PET scans of the brains of Parkinson's patients given an experimental gene therapy to improve muscular control showed that the treatment worked and had lasting results.

The study was conducted by researchers from The Feinstein Institute for Medical Research and the Weill Cornell Medical Center in the US. In the study, genes for glutamic acid decarboxylase (GAD) were delivered into the subthalamic nucleus of the brain in a dozen Parkinson's patients using a viral carrier. The genes were delivered to only one side of the brain to reduce risk and to better assess the treatment.

All the patients in the study received the gene therapy so, as there was no control group, the scientists knew that there could be a placebo effect. This made the brain scans so critical to the experiment to determine if the changes in the patients were caused by changes in the brain.

Dr David Eidelberg and his colleagues Dr Andrew Feigin and Dr Michael Kaplitt pioneered the technology and used it to identify brain networks in Parkinson's disease and a number of other neurological disorders. In Parkinson's, they identified two discrete brain networks — one that regulates movement and another that affects cognition.

The results from the brain scan study on the gene therapy patients show that only the motor networks were altered by the therapy. "This is good news," said Dr. Eidelberg, the senior investigator of the study. "You want to be sure that the treatment doesn't make things worse." The gene makes an inhibitory chemical called GABA that turns down the activity in a key node of the Parkinson's motor network. The investigators were not expecting to see changes in cognition, and the scans confirmed that this did not occur.

Position emission tomography (PET) scans were performed before the surgery and repeated six months later and then again one year after the surgery. The motor network on the untreated side of the body got worse, and the treated side got better. The level of improvements in the motor network correlated with increased clinical ratings of patient disability, added Dr Feigin.

"Having this information from a PET scan allows us to know that what we are seeing is real," Dr. Eidelberg added. The scans also detected differences in responses between dose groups, with the highest gene therapy dose demonstrating a longer-lasting effect. "This study demonstrates that PET scanning can be a valuable marker in testing novel therapies for Parkinson's disease," he said.

The study was published in the Proceedings of the National Academy of Sciences. The gene therapy technique was developed by Neurologix Inc., a New Jersey-based company. Scientists are now working on a design for a phase 2 blinded study that would include a larger number of patients to test the effectiveness of the treatment.

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