• Safety
  

• Improvement in brain metabolism measured by PET scans
  
• Improvement in standard clinical rating scales
  

This study involves treatment of patients with medically refractory Parkinson's disease (PD) with gene therapy. The patients are chosen from a population of patients who would normally be candidates for standard deep brain stimulation (DBS) surgery for PD. These patients respond to medical therapy, but develop substantially reduced responses over time, often with severe fluctuations in their condition between a functional and severely non-functional state. Some patients also develop dose-limiting side effects from medication, including involuntary movements called dyskinesias and nightmares. When there are no medical contraindications, DBS is often performed in these patients to try to quiet hyperactive brain regions such as the subthalamic nucleus (STN). In PD, the STN is overactive due to a loss of GABA inputs to this region, which normally reduces neuronal firing. In turn, the STN drives other brain regions, including the globus pallidus (GPi) and substantia nigra (SNr), which are also hyperactive and which also have reduced GABA inputs. The goal of this gene therapy trial is to introduce the gene for glutamic acid decarboxylase (GAD) into the STN using an adeno-associated virus (AAV) vector, in order to permit the STN to produce it's own GABA, as well as release GABA into the GPi and SNr targets, which also have reduced GABA inputs. This is anticipated to restore a more normal pattern of information flow from this basal ganglia circuit to the thalamus and higher cortical structures in order to reduce the motor symptoms of PD, while eliminating complications arising from inserting DBS electrodes and batteries into the human body.