Gene Therapy for Parkinson's Disease

(REGENERATE-PD Trial)

Recruiting at 38 trial locations

Overseen By Christian Urrea, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Asklepios Biopharmaceutical, Inc.

Must be taking: Antiparkinsonian

Must not be taking: Immunosuppressants

Disqualifiers: Vascular disease, Cognitive impairment, Psychosis, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

The objective of this randomized, surgically controlled, double-blinded, Phase 2 study is to evaluate the safety and efficacy of AAV2-GDNF delivered to the putamen in subjects with moderate Parkinson's Disease.

Will I have to stop taking my current medications?

The trial requires that participants have a stable anti-parkinsonian medication regimen for at least 4 weeks before screening, so you should not stop taking your current medications.

What data supports the effectiveness of the treatment AAV2-GDNF, AB-1005 for Parkinson's disease?

Research shows that using AAV2 to deliver the GDNF gene in animal models of Parkinson's disease can help protect and restore dopamine-producing neurons, leading to improved movement and brain function. This suggests that AAV2-GDNF could be a promising treatment for Parkinson's disease. ^{1 2 3 4 5}

Is AAV2-GDNF gene therapy safe for humans?

AAV2-GDNF gene therapy has shown a promising safety profile in animal studies, with no systemic toxicity observed and local effects at the injection site being reversible. In primate studies, no adverse immune responses were detected, although significant weight loss was noted with certain delivery methods. Long-term safety data from similar gene therapies in humans showed no unexpected adverse events, suggesting it can be administered safely. ^{2 5 6 7 8}

How is the treatment AAV2-GDNF different from other treatments for Parkinson's disease?

AAV2-GDNF is a gene therapy that uses a viral vector to deliver a gene encoding a neuroprotective protein directly into the brain, aiming to promote the survival and growth of dopamine-producing neurons, which is different from traditional treatments that typically focus on managing symptoms rather than addressing the underlying neuronal degeneration. ^{2 4 5 6 9}

Eligibility Criteria

Adults aged 45-75 with moderate Parkinson's Disease can join this trial. They should have specific scores on the MDS-UPDRS Part III in an OFF state, experience motor fluctuations for over 2.5 hours daily, and respond to levodopa treatment. Those with severe disease stages or unstable medication regimens cannot participate.

Inclusion Criteria

My Parkinson's disease symptoms are moderate to severe when not on medication.

I am between 45 and 75 years old.

I experience stiffness, shaking at rest, and balance issues.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive AAV2-GDNF or undergo sham surgery to evaluate safety and efficacy

18 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Treatment Details

Interventions

• AAV2-GDNF (Virus Therapy)

Trial Overview The study is testing AAV2-GDNF gene therapy versus a control surgery to see if it's safe and effective for Parkinson's when delivered to a brain region called the putamen. It’s randomized and double-blinded, meaning neither participants nor researchers know who gets which treatment until after results are collected.

Participant Groups

Group I: AAV2-GDNF Experimental Treatment 1 Intervention

Group II: Control Surgery Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Asklepios Biopharmaceutical, Inc.

Lead Sponsor

Trials

8

Recruited

440+

AskBio Inc

Lead Sponsor

Trials

8

Recruited

440+

Bayer

Industry Sponsor

Trials

2,291

Recruited

25,560,000+

Founded

1863

Headquarters

Leverkusen, Germany

Known For

Pharmaceutical Innovations

Top Products

Aspirin, Aleve, Yaz, Nexavar

Bill Anderson

Bayer

Chief Executive Officer since 2023

BSc in Chemical Engineering from the University of Texas, MSc in Chemical Engineering and Management from MIT

Michael Devoy

Bayer

Chief Medical Officer since 2014

MD, PhD

Findings from Research

Recombinant viral vectors, specifically AAV and LV, have been shown to effectively deliver glial cell line-derived neurotrophic factor (GDNF) in rat models of Parkinson's disease, preventing degeneration of dopamine neurons and preserving striatal function.

Long-term delivery of GDNF using these vectors over 3-6 months resulted in significant functional recovery in both rats and monkeys, indicating their potential for neuroprotective treatments in human patients with Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Towards a neuroprotective gene therapy for Parkinson's disease: use of adenovirus, AAV and lentivirus vectors for gene transfer of GDNF to the nigrostriatal system in the rat Parkinson model. Björklund, A., Kirik, D., Rosenblad, C., et al.[2022]

Glial cell line-derived neurotrophic factor (GDNF) shows promise in protecting and regenerating dopamine neurons in animal models of Parkinson's disease, suggesting it could be a potential treatment for preserving and restoring function in patients.

Gene therapy using encapsulated, GDNF-secreting cells offers a novel approach for delivering GDNF, with the added safety feature of being able to remove the cells if adverse effects occur, paving the way for future clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Encapsulated cell biodelivery of GDNF: a novel clinical strategy for neuroprotection and neuroregeneration in Parkinson's disease? Lindvall, O., Wahlberg, LU.[2008]

Adeno-associated viral (AAV) vector-mediated delivery of the GDNF gene significantly improved the survival of dopaminergic neurons and increased dopamine levels in a rat model of Parkinson's disease, even when administered 4 weeks after neuron degeneration began.

Behavioral recovery in the rats was observed from 4 to 20 weeks post-injection, indicating that delayed GDNF delivery can effectively counteract the progression of Parkinson's disease symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delayed delivery of AAV-GDNF prevents nigral neurodegeneration and promotes functional recovery in a rat model of Parkinson's disease. Wang, L., Muramatsu, S., Lu, Y., et al.[2022]

In a study using a rat model of Parkinson's disease, administering rAAV-GDNF after a significant neurotoxic lesion led to notable behavioral recovery and increased dopaminergic markers within 4 weeks, indicating its potential efficacy in restoring dopamine function.

This research suggests that rAAV-GDNF gene therapy could effectively rescue dopaminergic neurons and improve motor function in conditions that closely mimic advanced Parkinson's disease, highlighting its therapeutic promise.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adeno-associated viral delivery of GDNF promotes recovery of dopaminergic phenotype following a unilateral 6-hydroxydopamine lesion. McGrath, J., Lintz, E., Hoffer, BJ., et al.[2019]

The study assessed the safety of AAV2-human GDNF in rats, finding no systemic toxicity and only reversible local toxicity at the injection site, indicating a promising safety profile for this treatment in Parkinson's disease models.

The lowest dose of 6.8 × 108 vector genomes per dose was identified as the no observed adverse effect level, suggesting it may be the safest option for further studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Assessment of AAV2-hGDNF Administered Via Intracerebral Injection in Rats for Treatment of Parkinson's Disease. Terse, PS., Kells, AP., Noker, P., et al.[2022]

A long-term safety assessment of rAAV2-neurturin in 53 patients with advanced Parkinson's disease showed that the treatment is generally safe, with only a few non-serious adverse events reported, none of which were definitively linked to the therapy.

Over a follow-up period of up to 5 years, patients demonstrated stable or modestly improved motor function, indicating that rAAV2-neurturin not only has a favorable safety profile but may also provide therapeutic benefits in managing Parkinson's disease symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Safety of Patients with Parkinson's Disease Receiving rAAV2-Neurturin (CERE-120) Gene Transfer. Marks, WJ., Baumann, TL., Bartus, RT.[2022]

In a study involving 17 aged rhesus macaques, the administration of AAV2-GDNF into the substantia nigra resulted in a significant weight loss of 19.4%, raising safety concerns for this method of treatment.

Conversely, in a separate study with 11 MPTP-lesioned macaques, AAV2-GDNF delivery to the putamen did not cause weight loss and showed potential therapeutic benefits, indicating that the method may be safer when targeting the putamen rather than the substantia nigra.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety evaluation of AAV2-GDNF gene transfer into the dopaminergic nigrostriatal pathway in aged and parkinsonian rhesus monkeys. Su, X., Kells, AP., Huang, EJ., et al.[2021]

AAV2-GDNF gene therapy safely delivers therapeutic levels of glial cell-derived neurotrophic factor (GDNF) to targeted brain areas in aged nonhuman primates, enhancing dopaminergic innervation without significant adverse effects.

High-dose AAV2-GDNF treatment increased the density of dopaminergic terminals and improved dopamine turnover in the putamen, suggesting potential benefits for restoring dopaminergic function in Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinically relevant effects of convection-enhanced delivery of AAV2-GDNF on the dopaminergic nigrostriatal pathway in aged rhesus monkeys. Johnston, LC., Eberling, J., Pivirotto, P., et al.[2021]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Towards a neuroprotective gene therapy for Parkinson's disease: use of adenovirus, AAV and lentivirus vectors for gene transfer of GDNF to the nigrostriatal system in the rat Parkinson model. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Glial-derived neurotrophic factor gene transfer for Parkinson's disease: anterograde distribution of AAV2 vectors in the primate brain. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Encapsulated cell biodelivery of GDNF: a novel clinical strategy for neuroprotection and neuroregeneration in Parkinson's disease? [2008]

4. England pubmed.ncbi.nlm.nih.gov

Delayed delivery of AAV-GDNF prevents nigral neurodegeneration and promotes functional recovery in a rat model of Parkinson's disease. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Adeno-associated viral delivery of GDNF promotes recovery of dopaminergic phenotype following a unilateral 6-hydroxydopamine lesion. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Safety Assessment of AAV2-hGDNF Administered Via Intracerebral Injection in Rats for Treatment of Parkinson's Disease. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Long-Term Safety of Patients with Parkinson's Disease Receiving rAAV2-Neurturin (CERE-120) Gene Transfer. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Safety evaluation of AAV2-GDNF gene transfer into the dopaminergic nigrostriatal pathway in aged and parkinsonian rhesus monkeys. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Clinically relevant effects of convection-enhanced delivery of AAV2-GDNF on the dopaminergic nigrostriatal pathway in aged rhesus monkeys. [2021]