PET Scans Show How Gene Therapy Normalizes Brain Function in Parkinson's Patients

Positron emission tomography (PET) scans of the brain used to monitor changes in 12 patients who received an experimental gene therapy revealed that the treatment normalizes brain function--and the effects are still present one year later.

Andrew Feigin, M.D., and David Eidelberg, M.D., from the Feinstein Institute for Medical Research (Manhasset, NY, USA) collaborated with Michael Kaplitt, M.D., from Weill Cornell Medical Center (New York, NY, USA) and others to deliver genes for glutamic acid decarboxylase (GAD) into the subthalamic nucleus of the brain in Parkinson's patients. The study was designed as a phase I safety study, and the genes were delivered to only one side of the brain to reduce risk and to better assess the treatment.

A recently published study included the clinical results of the novel gene therapy trial, but this new report from the same study focuses on the power of advanced brain scans to show that the gene therapy altered brain activity in a favorable way. The patients only received the viral vector-carrying genes to the side of the brain that controls movement on the side of their body most affected by the disease. It was a so-called open-label study--everybody received the gene therapy so the scientists knew that there could be a placebo effect. That is why brain scans were so vital to the study. Dr. Eidelberg and his colleagues pioneered the technology and used it to identify brain networks in Parkinson's disease and a number of other neurologic 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 revealed 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 ã-aminobutyric acid (GABA) that decreases 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.

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 gene therapy technique was developed by Neurologix, Inc. (Fort Lee, NJ, USA). Scientists are now working on a design for a phase II blinded study that would include a larger number of patients to assess the effectiveness of the treatment.


Related Links:
Feinstein Institute for Medical Research
Weill Cornell Medical Center
Neurologix