Safety and Efficacy Study of VY-AADC01 for Advanced Parkinson's Disease

Inclusion Criteria: * Diagnosed with idiopathic PD. * Adequate duration of levodopa therapy. * Disease duration of at least 5 years or more. * Modified Hoehn \& Yahr Staging with at least 2.5 hours or more in the OFF state. * Candidate for surgical intervention because of disabling motor complications. * UPDRS Part III (total score) of at least 25 in the OFF state. * Unequivocal responsiveness to dopaminergic therapy. * Stable Parkinson's symptoms and medications for at least 4 weeks prior to screening evaluation. * Ability to comprehend and sign the informed consent. * Normal laboratory values prior to surgery. * Medically and mentally capable of undergoing and complying with the surgical procedure and protocol requirements. * Ability to travel to study visits alone or able to designate a caregiver. * Subject agrees to defer any neurological surgery, including deep brain stimulation, until after completing the 12 month study visit (unless recommended by study neurologist). * Approved by the Eligibility Review Committee. Exclusion Criteria: * Atypical or secondary parkinsonism, including but not limited to symptoms believed to be due to trauma, brain tumor, infection, cerebrovascular disease, other neurological disease, or to drugs, chemicals, or toxins. * Presence of dementia as defined by a Mattis Dementia Rating Scale - Second Edition (MDRS-2) score of less than 130 at screening. * Presence or history of psychosis, with the exception of mild, benign hallucinations believed in the judgment of the Investigator to be related to Parkinson's medications. * Presence of severe depression, as indicated by a BDI-II score greater than 28, or a history of a major affective disorder within 5 years of screening evaluation. * Active suicidal ideation or suicide attempt within 5 years of screening evaluation. * History of substance abuse within 2 years of screening evaluation. * Brain imaging abnormalities in the striatum or other regions that would substantially increase risk of surgery. * Contraindication to MRI and/or gadoteridol. * Coagulopathy or inability to temporarily stop any anticoagulation or antiplatelet therapy prior to surgery. * Prior brain surgery including lesioning procedures, deep brain stimulation, infusion therapies or any other brain surgery. * Prior gene transfer. * History of stroke, poorly controlled or significant cardiovascular disease, diabetes, or any other acute or chronic medical condition. * History of malignancy other than treated carcinoma in situ within 3 years of screening evaluation. * Clinically apparent or laboratory-detected infection. * Prior or current treatment with any investigational agent within 2 months of screening evaluation. * Inability to comply with the procedures of the protocol, including completion of paper Parkinson's disease diaries, frequent and prolonged study visits including off medication visits, and travel. * Chronic immunosuppressive therapy, including chronic steroids, immunotherapy, cytotoxic therapy, and chemotherapy. * Any serious medical condition or abnormal finding on physical examination or laboratory investigation that would substantially increase the risks of the study procedures. * Any medical condition that is likely to lead to disability during the course of the study and interfere with or confound study assessments. * Pregnant and lactating women. * Male or female with reproductive capacity who is unwilling to use barrier contraception for 6 months after surgery. * Plans to receive any vaccination within 30 days of surgery. * Any factors, medical or social, which would likely cause the participant to be unable to follow the study protocol, including geographical inaccessibility. * Ongoing treatments including neuroleptic medications, apomorphine, or levodopa infusion therapy (Duopa®). * Plans to participate in any other therapeutic intervention study within 12 months after surgery.