for people ages 40-75 (full criteria)
at San Francisco, California and other locations
study started
estimated completion
Principal Investigator
by Paul Larson
Headshot of Paul Larson
Paul Larson



Safety and efficacy of AADC gene transfer in participants with Parkinson's disease.

Official Title

An Open-label Safety and Efficacy Study of VY-AADC01 Administered by MRI-Guided Convective Infusion Using a Posterior Trajectory Into the Putamen of Participants With Parkinson's Disease With Fluctuating Responses to Levodopa


Parkinson's disease (PD) is a neurodegenerative disorder involving loss of dopamine producing neurons located in the striatum. Levodopa is the primary treatment used to treat Parkinson's disease, which converts to dopamine by the enzyme (protein) Aromatic L-Amino Acid Decarboxylase (AADC). As PD progresses, the amount of AADC levels in the brain decreases, and in turn, reduces the amount of dopamine that is produced with each dose of levodopa. The primary objective of this study is to evaluate the safety of increasing AADC levels, via gene delivery. The investigational drug, termed VY-AADC-01, will be injected directly into the striatum during a neurosurgical procedure that is performed with real-time MRI imaging to monitor delivery. Participants will continue to take their Parkinson medications, including levodopa while participating in this study. The safety and potential clinical responses to VY-AADC-01 will be assessed by repeated clinical evaluations of Parkinson's disease, treatment review phone calls, cognitive tests, laboratory blood tests, patient reported outcomes scales, patient diaries, collection of adverse events, and neuro-imaging. Clinical evaluations will be performed over a 3 year follow-up period.


Idiopathic Parkinson's Disease Parkinson's Disease Basal Ganglia Disease Brain Diseases Central Nervous System Diseases Movement Disorders Nervous System Diseases Neurodegenerative Diseases Parkinsonian Disorders Gene Therapy PD Aromatic L- Amino Acid Decarboxylase AADC AAV2-AADC AAV2 Viral Vector Gene Transfer MRI PET VY-AADC01 Parkinson Disease Basal Ganglia Diseases Disease


You can join if…

Open to people ages 40-75

  • 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.

You CAN'T join if...

  • 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.


  • University of California, San Francisco (UCSF)
    San Francisco California 94143 United States
  • Ohio State University (OSU)
    Columbus Ohio 43210 United States

Lead Scientist at UCSF

  • Paul Larson
    Professor, Neurological Surgery. Authored (or co-authored) 105 research publications. Research interests: Deep brain stimulation · MRI-guided surgery · Gene therapy · Parkinson's disease · Essential tremor · Tinnitus.


in progress, not accepting new patients
Start Date
Completion Date
Neurocrine Biosciences
Company Website
Phase 1
Study Type
Last Updated