In the Phase I study, the investigators injected an adeno-associated virus (AAV) vector carrying an inhibitory gene (glutamic acid decarboxylase or GAD) into one side of the subthalmic nucleus (STN) of the brain of 12 patients with advanced Parkinson’s disease. The GAD gene was intended to increase the synthesis of the major inhibitory neurotransmitter in the brain, gamma-aminobutyric acid and thus calm the overactive STN.
Although all patients had symptoms on both sides of their bodies, the gene transfer procedure was performed on only one side of the brain, enabling the untreated side to serve as a study control. Improvements in both clinical symptoms and abnormal brain network activity were seen predominately on the treated side of the brain at six months following treatment. Both the clinical benefit and the metabolic improvement persisted through the 12 months of the study period. Moreover, the improvements in brain metabolism occurred in areas of the motor network different from those known to be produced by brain lesioning alone. At the same time, the activity of the cognition-related brain network did not change following the gene transfer procedure.
John Mordock, president and CEO of Neurologix, said: “We are very encouraged by these findings. They suggest a highly useful, measurable biomarker of efficacy for use in subsequent studies of our gene transfer approach to the treatment of Parkinson’s disease and potentially other neurodegenerative conditions. We expect to begin a Phase II study of our approach in Parkinson’s disease within the coming weeks, and believe that we are on track to begin a Phase I study in epilepsy.”