PET Scans Show Gene Therapy Normalizes Brain
Function in Parkinson’s
Study focuses on power of modern brain scans to show
that gene therapy altered brain activity in a favorable way
Nov. 20, 2007 - 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. 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., 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
http://www.FeinsteinInstitute.org
or the Feinstein Institute’s blog at
http://feinsteininstitute.typepad.com/feinsteinweblog/
