Phase
Observational (Long-Term Follow-up)
Status
Enrolling by invitation
Intervention
AAV2-GDNF (AB-1005) gene therapy follow-up
Indication
Parkinson's Disease, MSA-P
Enrollment
132 participants (estimated)
Study Start
September 4, 2025
Est. Completion
March 30, 2038
AB-1005 (also known as AAV2-GDNF) is an adeno-associated virus serotype 2 (AAV2)-based gene therapy that delivers the Glial Cell Line-Derived Neurotrophic Factor (GDNF) gene directly to the putamen of patients with Parkinson's Disease (PD) or Multiple System Atrophy of the Parkinson variant (MSA-P). This long-term follow-up study (NCT07081841) is tracking the safety and efficacy of participants who previously received AB-1005 gene transfer in earlier interventional trials.
GDNF is a potent neurotrophic factor that promotes the survival and function of dopaminergic neurons, which degenerate in Parkinson's disease. By delivering the GDNF gene via AAV2, the therapy enables continuous local production of GDNF protein in the target brain region, potentially providing long-lasting neuroprotective effects.
- Phase: Long-term Follow-up (Observational)
- Status: Enrolling by invitation
- Study Type: Observational
- Sponsor: AskBio Inc.
- Collaborator: Bayer
- ClinicalTrials.gov Identifier: NCT07081841
- Official Title: Long-Term Safety and Efficacy Follow-up of AB-1005 Gene Transfer Study Participants With Parkinson's Disease or Multiple System Atrophy
- Enrollment: 132 participants (estimated)
- Study Start Date: September 4, 2025
- Estimated Completion: March 30, 2038
This observational study is designed to:
- Monitor Long-Term Safety — Assess the continued safety profile of AB-1005 gene transfer over extended follow-up periods
- Evaluate Durability of Efficacy — Determine whether the therapeutic benefits observed in the initial trials are sustained over time
- Characterize Disease Progression — Compare the natural history of PD/MSA in treated versus untreated patients
- Identify Late Effects — Detect any delayed adverse events that may emerge years after treatment
The study includes participants from:
- REGENERATE-PD (NCT04815625) — Phase 2 trial of AAV2-GDNF for Parkinson's disease
- NCT07215403 — PIA (Prescriptive Infusion Algorithm) study optimizing delivery techniques
- Other AB-1005 interventional studies
Patient populations:
- Parkinson's Disease (PD)
- Multiple System Atrophy, Parkinson variant (MSA-P)
Participants must meet the following criteria to be eligible for this long-term follow-up study:
- Prior AB-1005 Treatment — Previous participation in an interventional AB-1005 gene therapy study
- Ability to Comply — Willing and able to attend follow-up visits
- Informed Consent — Able to provide continued informed consent
- Withdrawal from Prior Study — Previously withdrawn from AB-1005 interventional studies
- Contraindications — Medical conditions precluding follow-up assessments
- Concomitant Exclusions — Participation in other interventional trials
Participants undergo regular assessments including:
- Neurological Examinations — Comprehensive motor and non-motor evaluations
- Imaging Studies — MRI and PET scans to monitor brain structure and function
- Clinical Rating Scales — UPDRS (Unified Parkinson's Disease Rating Scale), MDS-UPDRS
- Quality of Life Measures — PDQ-39, non-motor symptom scales
- Biomarker Sampling — CSF and blood biomarkers where available
- Safety Monitoring — Adverse event collection and analysis
AB-1005 employs AAV2-mediated gene delivery to achieve sustained GDNF expression:
- Vector Delivery — AAV2 serotype engineered to carry the human GDNF gene
- Stereotactic Injection — Direct delivery to bilateral putamen using precision neurosurgery
- Cellular Transduction — AAV2 enters neurons and other glial cells
- Gene Expression — Cells begin producing GDNF protein from the delivered gene
- Neurotrophic Effects — GDNF promotes dopaminergic neuron survival, axonal outgrowth, and function
| Aspect |
Historical GDNF Trials |
AB-1005 Gene Therapy |
| Delivery Method |
Continuous protein infusion |
Single gene transfer procedure |
| GDNF Source |
Recombinant protein |
Endogenous production from transduced cells |
| Treatment Duration |
Requires ongoing infusions |
Potential long-term expression from single treatment |
| Targeting |
Variable distribution |
Precision putaminal delivery |
| Surgical Burden |
External devices needed |
Single stereotactic procedure |
| Year |
Milestone |
| 2019-2020 |
Preclinical studies demonstrating efficacy |
| 2021 |
IND application cleared |
| 2022-2023 |
REGENERATE-PD Phase 2 initiation |
| 2024 |
First patient treated in REGENERATE-PD |
| 2025 |
Long-term follow-up study initiated (NCT07081841) |
| 2026 |
PIA study (NCT07215403) begins enrollment |
Currently enrolled sites include:
- San Francisco, California, United States
- Columbus, Ohio, United States
Additional sites may be added as the program expands.
- Long-term Safety and Tolerability — Incidence and severity of adverse events
- Serious Adverse Events — Characterize any SAEs related to treatment
- Motor Function — Change in MDS-UPDRS scores from baseline
- Off-Medication UPDRS — Assessment of untreated motor function
- Quality of Life — PDQ-39 total score and subdomain scores
- Imaging Biomarkers — DaTscan, FDG-PET changes
- CSF Biomarkers — Alpha-synuclein, neurofilament light chain (NfL)
- Cognitive Function — MoCA, neuropsychological testing
This long-term follow-up study is critical for:
- Understanding Durability — Determining if neurotrophic factor therapy provides lasting benefits
- Optimizing Patient Selection — Identifying which patients benefit most from treatment
- Refining Delivery Techniques — Improving targeting and distribution
- Regulatory Decisions — Providing data for potential FDA/EMA approval
AB-1005 represents one of the most advanced CNS-directed gene therapy programs:
- Proof of Concept — Demonstrates feasibility of neurotrophic factor gene delivery
- Delivery Innovation — Pioneers convection-enhanced and prescriptive infusion approaches
- Regulatory Pathway — Establishes precedent for approval of CNS gene therapies
| Trial ID |
Title |
Phase |
Status |
| NCT04815625 |
REGENERATE-PD |
Phase 2 |
Active |
| NCT07215403 |
PIA Study |
Phase 2 |
Not yet recruiting |
| NCT07081841 |
Long-Term Follow-up |
Observational |
Enrolling |
¶ Challenges and Considerations
- Gene Expression Duration — Long-term stability of GDNF production
- Immune Response — Potential for neutralizing antibodies against AAV2
- Disease Modification — Whether effects are truly disease-modifying vs. symptomatic
- Patient Heterogeneity — Variable response across patient populations
- Follow-up Compliance — Maintaining patient engagement over 10+ years
- Standard of Care Evolution — Accounting for new PD therapies during follow-up
- Data Collection — Consistent methodology across multiple sites
- Analytical Approaches — Appropriate statistical methods for observational data