AB-1005 GDNF Gene Therapy Long-Term Follow-up Study

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clinical1235 wordssynced 2026-04-02

<div class="infobox infobox-trial">
<div class="infobox-header">Long-Term Follow-up Study</div>
<div class="infobox-row">
<div class="infobox-label">NCT Number</div>
<div class="infobox-value">NCT07081841</div>
</div>
<div class="infobox-row">
<div class="infobox-label">Phase</div>
<div class="infobox-value">Observational (Long-Term Follow-up)</div>
</div>
<div class="infobox-row">
<div class="infobox-label">Status</div>
<div class="infobox-value">Enrolling by invitation</div>
</div>
<div class="infobox-row">
<div class="infobox-label">Sponsor</div>
<div class="infobox-value">AskBio Inc.</div>
</div>
<div class="infobox-row">
<div class="infobox-label">Collaborator</div>
<div class="infobox-value">Bayer</div>
</div>
<div class="infobox-row">
<div class="infobox-label">Intervention</div>
<div class="infobox-value">AAV2-GDNF (AB-1005) gene therapy follow-up</div>
</div>
<div class="infobox-row">
<div class="infobox-label">Indication</div>
<div class="infobox-value">Parkinson's Disease, MSA-P</div>
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<div class="infobox-row">
<div class="infobox-label">Enrollment</div>
<div class="infobox-value">132 participants (estimated)</div>
</div>
<div class="infobox-row">
<div class="infobox-label">Study Start</div>
<div class="infobox-value">September 4, 2025</div>
</div>
<div class="infobox-row">
<div class="infobox-label">Est. Completion</div>
<div class="infobox-value">March 30, 2038</div>
</div>
</div>

Overview

...

Overview

Mermaid diagram (expand to render)

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["@longterm"][@hovde2024].

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["@bartus2013"].

Trial Details

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

Study Design

Purpose

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

Study Population

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)

Eligibility Criteria

Inclusion Criteria (General for Long-Term Follow-up)

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

Exclusion Criteria

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

Assessment Schedule

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 Gene Therapy Background

Mechanism of Action

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

Key Advantages Over Historical GDNF Approaches

| 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 |

Clinical Development Timeline

| 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 |

Clinical Sites

Currently enrolled sites include:

San Francisco, California, United States
Columbus, Ohio, United States

Additional sites may be added as the program expands.

Outcome Measures

Primary Outcomes

Long-term Safety and Tolerability — Incidence and severity of adverse events
Serious Adverse Events — Characterize any SAEs related to treatment

Secondary Outcomes

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

Scientific Significance

For Parkinson's Disease

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

For Gene Therapy Field

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

Scientific Challenges

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

Practical Considerations

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

External Links

[ClinicalTrials.gov - NCT07081841](https://clinicaltrials.gov/study/NCT07081841)
[AskBio Inc. - Gene Therapy Pipeline](https://www.askbio.com)
[Michael J. Fox Foundation - GDNF Research](https://www.michaeljfox.org/research-funding)
[Parkinson's Foundation - Treatment Advances](https://www.parkinson.org/)

References

Unknown, AB-1005 Long-Term Follow-up Study (NCT07081841) (n.d.)

[Hovde S, et al., (2024). AB-1005 gene therapy for Parkinson's disease: first patient treated. Brain. 147(6):1523-1535 (2024)](https://pubmed.ncbi.nlm.nih.gov/38547652/)

[Bartus RT, et al., (2013). Beyond the 6-OHDA model of Parkinson's disease: GDNF and AAV-GDNF. Mol Ther. 21(3):498-505 (2013)](https://pubmed.ncbi.nlm.nih.gov/23292652/)

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AB-1005 GDNF Gene Therapy Long-Term Follow-up Study

Overview

Overview

Trial Details

Study Design

Purpose

Study Population

Eligibility Criteria

Inclusion Criteria (General for Long-Term Follow-up)

Exclusion Criteria

Assessment Schedule

AB-1005 Gene Therapy Background

Mechanism of Action

Key Advantages Over Historical GDNF Approaches

Clinical Development Timeline

Clinical Sites

Outcome Measures

Primary Outcomes

Secondary Outcomes

Scientific Significance

For Parkinson's Disease

For Gene Therapy Field

Related Trials

Challenges and Considerations

Scientific Challenges

Practical Considerations

See Also

External Links

References