Safety Study of AADC Gene Therapy (VY-AADC01) for Parkinson's Disease

Inclusion Criteria: * Diagnosed with idiopathic Parkinson's disease * Disease duration of at least 5 years or more * Adequate duration of levodopa therapy * Modified Hoehn and Yahr Staging of at least 2.5 in the OFF state * Candidate for surgical intervention because of disabling motor complications. * UPDRS Part III (total motor) score ≥ 25 and a maximum of 60 in the OFF state. * Unequivocal responsiveness to dopaminergic therapy. * Stable Parkinson's symptoms and medication regimen for at least 4 weeks prior to screening examination. * Ability to comprehend and sign the informed consent. * Normal Laboratory values prior to surgery. * Neutralizing AAV2 antibody titer ≤ 1:1200 * 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). * Subject agrees to not participate in any other therapeutic intervention study for 12 months after surgery. * Subject agrees to not have any vaccinations within 30 days of surgery. 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) of less than 130 at screening. * Presence or history of psychosis, with the exception of mild, benign hallucinations believed in the judgment of the investigators to be related to Parkinson's medications. * Presence of severe depression as measured by Beck Depression Inventory II (BDI-II) \> 28 or a history of a major affective disorder within 5 years of screening examination. * Current suicidal ideation or suicide attempt within 5 years of screening examination. * History of substance abuse within 2 years of screening examination. * 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 prior to surgery. * Prior brain surgery including 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 three years of screening evaluation. * Clinically apparent or laboratory-detected infection. * Prior or current treatment with any investigational agent within 2 months of screening evaluation. * Chronic immunosuppressive therapy, including chronic steroids, immunotherapy, cytotoxic therapy and chemotherapy. * Pregnant and lactating women. * Subject with reproductive capacity who is unwilling to use barrier contraception. * Any medical condition that is likely to lead to disability during the course of the study and interfere with confound study assessments * Any factors, medical, or social, which would likely cause the subject to be unable to follow the study protocol, including geographical inaccessibility. * Ongoing treatments such as, neuroleptic medications, apomorphine, or levodopa infusion therapy (Duodopa®).