Study of AAV-GAD Gene Transfer Into the Subthalamic Nucleus for Parkinson's Disease

Phase 2 Safety and Efficacy Study Evaluating Glutamic Acid Decarboxylase Gene Transfer to Subthalamic Nuclei in Subjects With Advanced Parkinson's Disease

The purpose of this study is to determine the safety and efficacy of AAV-GAD gene transfer into the subthalamic nucleus (STN) region of the brain. This study involves the treatment of subjects with medically refractory Parkinson's disease (PD). The gene transfer product, a disabled virus with a gene called GAD, will be infused into the STN bilaterally using stereotactic surgical techniques. The overall goal of this approach is to normalize the activity of the STN and reduce the motor symptoms of PD.

Because the change in UPDRS demonstrated a positive outcome, the sham surgery subjects from the blinded portion of the study will be invited to crossover into the Open-label Arm portion of the study. The Open-label Arm will further evaluate the safety and efficacy of AAV-GAD gene transfer into the subthalamic nucleus (STN) region of the brain.

Inclusion Criteria:

• Idiopathic Parkinson's disease
• Duration of disease for at least 5 years
• Levodopa responsiveness for at least 12 months
• UPDRS Part 3 score ≥ 25 or more in "off" state

Exclusion Criteria:

• Past history of brain surgery for PD
• Beck Depression Inventory Score ≥ 20
• Any history of cerebral insult or central nervous system infection
• Cognitive impairment score < 130 on the Mattis Dementia Rating Scale
• Focal neurological deficits
• Evidence of significant medical or psychiatric disorders
• Secondary Parkinsonism
• Atypical Parkinson's disease
• History of substance abuse