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

Nov 19, 2007, 00:00 ET from The Feinstein Institute for Medical Research

    MANHASSET, N.Y., Nov. 19 /PRNewswire-USNewswire/ -- Brain scans used to
 track changes in a dozen patients who received an experimental gene therapy
 show that the treatment normalizes brain function -- and the effects are
 still present a year later.
     Andrew Feigin, MD, and David Eidelberg, MD, of The Feinstein Institute
 for Medical Research collaborated with Michael Kaplitt, MD, of Weill
 Cornell Medical Center in Manhattan and others to deliver genes for
 glutamic acid decarboxylase (or 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 modern brain scans to show that the gene therapy altered brain
 activity in a favorable way. This latest study is published this week in
 the Proceedings of the National Academy of Sciences.
     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 critical to the experiment. Dr.
 Eidelberg and his colleagues 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.
     "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., 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.
     About The Feinstein Institute for Medical Research
     The Feinstein Institute for Medical Research is home to international
 scientific leaders in Parkinson's disease, Alzheimer's, psychiatric
 disorders, rheumatoid arthritis, lupus, sepsis, inflammatory bowel disease,
 diabetes, human genetics, leukemia, lymphoma, neuroimmunology, and
 medicinal chemistry. Part of the North Shore-LIJ Health System, FIMR ranks
 in the top 6th percentile of all National Institutes of Health grants
 awarded to research centers. Feinstein researchers are developing new drugs
 and drug targets, and producing results where science meets the patient.
 For more information, please visit or the
 Feinstein Institute's blog at

SOURCE The Feinstein Institute for Medical Research