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