Monday, 13 October 2008
New Gene Therapy Study Begins
Neurologix is starting a second clinical trial of its experimental gene
therapy for PD. The theory is that an inhibitory gene (glutamic acid
decarbolylase or "GAD") can be used to selectively mimic normal physiology
and alter the neural circuitry affected in Parkinson's disease. The GAD gene
into an AAV-based viral vector, and this packaged vector is introduced
directly into the subthalamic nucleus ("STN"). The GAD gene is responsible
for synthesizing gamma aminobutyric acid ("GABA"), which is released by
nerve cells to inhibit or dampen activity.
The loss of dopamine leads to a change in the activity of several brain
structures which control movement. Central to this is the STN, which is
overactive and does not receive adequate GABA, as well as targets of the
STN, which are also hyperactive and also do not receive enough GABA. The
goal of the study therapy is to deliver GABA to the STN in order to
re-establish the normal neurochemical balance and activity among these key
structures.
The study study is a double blind comparison against a saline (sterile salt
water solution) infusion and will also use an experimental device that is
made up of a tube and a pump. The study is seeking volunteers with
Parkinson's disease living in the USA. Details are available here.
Results of the previous study were reported in 2007 (The Lancet, June 23rd).
Twelve patients with advanced bilateral Parkinson's disease were treated ,
with four patients in each of three dose-escalating cohorts. Although
patients had bilateral disease treatment was limited to one side of the
brain in this first study All procedures were performed under local
anesthesia and all 12 patients were discharged from the hospital within 48
hours of the procedure. At one year, all 12 patients as a group demonstrated
a clinical improvement of 25% in the Unified Parkinson's Disease Rating
Scale (UPDRS) compared to baseline (p less than 0.005). Nine of the 12
patients showed an average of 37% and five of these patients had substantial
improvement of between 40% and 65%. Clinical improvement also correlated
well to metabolic changes in glucose utilization as measured by PET scan.
The PET scan data revealed a significant improvement (p less than 0.001) in
brain metabolism on the treated side of the brain compared to the untreated
side. No adverse events related to the gene therapy procedure were reported
throughout the duration of the 12-month study, or in the subsequent two
years since the study formally ended.
Rayilyn Brown
Director AZNPF
Arizona Chapter National Parkinson Foundation
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