GDNF Gene Therapy for Parkinson's Disease

Open-Label Safety Study of Glial Cell Line-Derived Neurotrophic Factor Gene Transfer (AAV2- GDNF) in Parkinson's Disease

The objective of this Phase 1b investigation is to evaluate the safety and potential clinical effect of AAV2-GDNF delivered to the putamen in subjects with either a recent or a long-standing diagnosis of PD.

Study Overview

• Status: Active, not recruiting
• Conditions: Parkinson's Disease
• Intervention / Treatment: Biological: AAV2-GDNF

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Irvine, California, United States, 92697
      • University of California Irvine
    • San Francisco, California, United States, 94103
      • University of California San Francisco
  • Ohio
    • Columbus, Ohio, United States, 43210
      • The Ohio State University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

• Male and female adults 35-75 years of age (inclusive)
• Diagnosed with Parkinson's disease
• Modified Hoehn and Yahr stage I-III OFF medication

• Time since receiving a clinical diagnosis of PD and disease severity consistent with one of the following:

  1. EITHER: Less than 5 years since clinical diagnosis of PD and mild to moderate UPDRS III OFF score
  2. OR: At least 4 years since clinical diagnosis of PD and moderate to severe UPDRS III OFF score
• Responsiveness to levodopa

Key Exclusion Criteria:

• Atypical parkinsonism
• Severe dyskinesia
• Presence of dementia, psychosis, substance abuse or qualify as "severe depression"
• Prior brain surgery (i.e. deep brain stimulator or DBS implantation) or other brain imaging abnormalities
• Receiving an investigational drug
• History of cancer or poorly controlled medical conditions that would increase surgical risk
• Inability to tolerate laying flat in an MRI or allergy to gadolinium

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Earlier stage PD	Biological: AAV2-GDNF; Bilateral image-guided infusion of AAV2-GDNF into putamen, single dose
Experimental: Later stage PD	Biological: AAV2-GDNF; Bilateral image-guided infusion of AAV2-GDNF into putamen, single dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The incidence of Treatment-Emergent Adverse Events (TEAE) assessed clinically by physical and neurological examinations	Evaluation of the safety and tolerability through the assessment of incidence of TEAE, identified by MedDRA preferred term and grouped by MedDRA System Organ Class, as well as clinically meaningful changes in clinical exams or laboratory assays.	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Motor symptoms as assessed by the Movement Disorder Society's Unified Parkinson's Disease Rating Scale (MDS-UPDRS)	Change from baseline in the MDS-UPDRS. The MDS-UPDRS contains 4 subscales: Part I, non-motor aspects of experiences of daily living (13 items); Part II, motor aspects of experiences of daily living (13 items); Part III, motor examination (33 scores based on 18 items); Part IV, motor complications (6 items). The rating for each item, or sub-item, is from 0 (normal) to 4 (severe). The total score for each Part is obtained from the sum of the corresponding item scores.	18 months
Non-motor symptoms of Parkinson's disease as assessed by the Non-Motor Symptom Scale (NMSS)	Change from baseline in the NMSS. The NMSS evaluates 9 domains of non-motor of severity and frequency of PD symptoms associated with cardiovascular health, sleep and fatigue, mood and cognition, perceptual problems and hallucinations, attention and memory, gastrointestinal tract, urinary, sexual function, and a miscellaneous domain for other common non-motor conditions. Severity x frequency scores range 0-108, with 0 being less severe and less frequent.	18 months
Brain dopaminergic cell integrity as measured by DaTscan	Percentage and absolute changes in Ioflupane retention as a marker for dopamine transporter protein expressed by dopamine producing cells within the brain. Measured by quantitative analysis of DaTscan SPECT imaging.	18 months

Collaborators and Investigators

• Sponsor: Brain Neurotherapy Bio, Inc.
• Collaborators: California Institute for Regenerative Medicine (CIRM); AskBio Inc

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2020
• Primary Completion (Actual): October 17, 2023
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: November 7, 2019
• First Submitted That Met QC Criteria: November 14, 2019
• First Posted (Actual): November 19, 2019

Study Record Updates

• Last Update Posted (Estimated): September 19, 2025
• Last Update Submitted That Met QC Criteria: September 16, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Parkinson's disease; AAV; Gene therapy; PD; GDNF; Growth factor; Neurotrophic factor; Glial cell line-derived neurotrophic factor
• Additional Relevant MeSH Terms: Synucleinopathies; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; Movement Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Parkinson Disease
• Other Study ID Numbers: GDNF-102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No