Evidence map›Paper›PMID 30802998›Full record

ArticleAnnals of neurology2019

Magnetic resonance imaging-guided phase 1 trial of putaminal AADC gene therapy for Parkinson's disease.

Chadwick W Christine, Krystof S Bankiewicz, Amber D Van Laar, R Mark Richardson, Bernard Ravina, Adrian P Kells, Brendon Boot, Alastair J Martin, John Nutt, Marin E Thompson and 1 more

2 registry-linked trialsOpen access · hybridAbstract readClinical Trial, Phase I
PubMed Full text at PMC Publisher
In one paragraph

Article in Annals of neurology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 92 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
92citing papers in PubMed, 1 pooled it
13.3field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01973543 phase1completednot on this map

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

TypeinterventionalSponsorNeurocrine BiosciencesRan2013 to 2020Enrolled15ConditionsParkinson's DiseaseArmsVY-AADC01
NCT03733496 completednot on this map

An Observational, Long-Term Extension Study for Participants in Prior VY-AADC01 Clinical Studies

TypeobservationalSponsorNeurocrine BiosciencesRan2018 to 2023Enrolled14ConditionsParkinson's Disease
3 · Its place in the literature

Who cites it

92 citing papers in PubMed, 1 synthesis or guideline pooled it, 155 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Review
  4. Article
  5. Review
  6. Article
  7. Review
  8. Clinical GDNF delivery methods for Parkinson's disease.Journal of Parkinson's disease · 2026
    Review
  9. Review
  10. Article
  11. Article
  12. Review
  13. Review
  14. Review
  15. Article
  16. Recent developments in gene therapy for Parkinson's disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2025
    Review
  17. Review
  18. Review
  19. Review
  20. Review

32 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 5 institutions in 1 country.

Chadwick W ChristineDepartment of Neurology, University of California, San Francisco.
Krystof S BankiewiczDepartment of Neurological Surgery, University of California, San Francisco.
Amber D Van LaarDepartment of Neurology, University of Pittsburgh.
R Mark RichardsonDepartment of Neurological Surgery, University of Pittsburgh.
Bernard RavinaVoyager Therapeutics, Inc.
Adrian P KellsVoyager Therapeutics, Inc.
Brendon BootVoyager Therapeutics, Inc.
Alastair J MartinDepartment of Radiology and Biomedical Imaging, University of California, San Francisco.
John NuttDepartment of Neurology, Oregon Health Sciences University.
Marin E ThompsonDepartment of Neurological Surgery, University of California, San Francisco.
Paul S LarsonDepartment of Neurological Surgery, University of California, San Francisco.
University of California, San Francisco · USUniversity of Pittsburgh · USNeurological Surgery · USOregon Health & Science University · USUniversity of California System · US

Funding

Oregon Clinical and Translational Research Institute - The National COVID Cohort Collaborative (N3C)UL1TR002369 · NCATS · OREGON HEALTH & SCIENCE UNIVERSITY · PI Cynthia D Morris, Christopher G. Slatore · 2017 to 2026
$78.4M
Michael J Fox FoundationNCATS NIH HHS UL1 TR002369Voyager Therapeutics
6 · The paper itself

Abstract

objectiveTo understand the safety, putaminal coverage, and enzyme expression of adeno-associated viral vector serotype-2 encoding the complementary DNA for the enzyme, aromatic L-amino acid decarboxylase (VY-AADC01), delivered using novel intraoperative monitoring to optimize delivery.

methodsFifteen subjects (three cohorts of 5) with moderately advanced Parkinson's disease and medically refractory motor fluctuations received VY-AADC01 bilaterally coadministered with gadoteridol to the putamen using intraoperative magnetic resonance imaging (MRI) guidance to visualize the anatomic spread of the infusate and calculate coverage. Cohort 1 received 8.3 × 10

resultsMRI-guided administration of ascending VY-AADC01 doses resulted in putaminal coverage of 21% (cohort 1), 34% (cohort 2), and 42% (cohort 3). Cohorts 1, 2, and 3 showed corresponding increases in enzyme activity assessed by PET of 13%, 56%, and 79%, and reductions in antiparkinsonian medication of -15%, -33%, and -42%, respectively, at 6 months. At 12 months, there were dose-related improvements in clinical outcomes, including increases in patient-reported ON-time without troublesome dyskinesia (1.6, 3.3, and 1.5 hours, respectively) and quality of life.

interpretationNovel intraoperative monitoring of administration facilitated targeted delivery of VY-AADC01 in this phase 1 study, which was well tolerated. Increases in enzyme expression and clinical improvements were dose dependent. ClinicalTrials.gov Identifier: NCT01973543 Ann Neurol 2019;85:704-714.

Indexed as

AdultAgedAromatic-L-Amino-Acid DecarboxylasesFemaleGenetic TherapyGene Transfer TechniquesHumansMagnetic Resonance ImagingMaleMiddle AgedParkinson DiseasePutamenAromatic-L-Amino-Acid DecarboxylasesDDC protein, human

Identifiers

PMID30802998
PMCPMC6593762
OpenAlexW2916632122

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.