Gene Therapy for Parkinson's Disease

(REGENERATE-PD Trial)

Recruiting at 57 trial locations

Overseen By Amber Van Laar, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Asklepios Biopharmaceutical, Inc.

Must be taking: Antiparkinsonian

Must not be taking: Immunosuppressants

Disqualifiers: Vascular disease, Cognitive impairment, Psychosis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 18 months

87 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new gene therapy treatment called AAV2-GDNF for individuals with moderate Parkinson's Disease. The aim is to determine if this treatment is safe and effective in easing symptoms such as tremors and movement difficulties. Participants will either receive the gene therapy or undergo a control surgery without the treatment. This trial suits those who have had Parkinson's for 4-10 years, experience movement issues, and find some relief from current treatments. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that AAV2-GDNF is likely to be safe for humans?

Research has shown that the treatment AAV2-GDNF is generally safe for people with Parkinson's disease. In earlier studies, participants handled the therapy well, and researchers found no major safety problems. These studies involved patients with mild to moderate Parkinson's disease, who either maintained their condition or even improved.

Although the treatment remains under study, the results so far are encouraging regarding safety. No serious side effects have been directly linked to AAV2-GDNF, suggesting it could be a safe option for those considering joining this trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Parkinson's Disease?

Unlike the standard treatments for Parkinson's disease, which typically involve medications like Levodopa to manage symptoms, AAV2-GDNF is unique because it uses gene therapy to address the condition at a deeper level. This treatment involves delivering the gene for Glial Cell Line-Derived Neurotrophic Factor (GDNF) directly into the brain using an adeno-associated virus (AAV) vector. This approach aims to protect and potentially restore damaged neurons, offering hope for a more long-lasting impact on the disease's progression. Researchers are excited because, unlike traditional treatments that primarily alleviate symptoms, AAV2-GDNF targets the underlying neurodegeneration, potentially offering a more effective and durable solution for patients.

What evidence suggests that AAV2-GDNF might be an effective treatment for Parkinson's Disease?

Research has shown promising results for AAV2-GDNF, one of the treatments studied in this trial, as a treatment for Parkinson's disease. Studies indicate that this gene therapy is generally safe for patients with moderate Parkinson's. The treatment delivers a protein called GDNF to protect brain cells, potentially slowing the disease. Early findings suggest that patients with mild Parkinson's remain stable, while those with moderate cases may see some improvement. These initial results make AAV2-GDNF a hopeful option for managing Parkinson's symptoms. Participants in this trial may receive either the AAV2-GDNF treatment or undergo a control surgery as part of the study's design. ^{1 2 4 5 6}

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• AAV2-GDNF

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

Direct gene delivery of AAV2-glial-derived neurotrophic factor (GDNF) to the brain shows promise for treating Parkinson's disease, with successful transport and expression observed in key brain regions after targeted delivery.

Using real-time image-guided techniques improved the accuracy of gene transfer, which is crucial since previous trials failed due to insufficient coverage of the target area, highlighting the importance of delivery methods in achieving therapeutic efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glial-derived neurotrophic factor gene transfer for Parkinson's disease: anterograde distribution of AAV2 vectors in the primate brain. Kells, AP., Forsayeth, J., Bankiewicz, KS.[2021]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. askbio.com askbio.com/askbio-presents-18-month-phase-ib-trial-results-of-ab-1005-gene-therapy-for-patients-with-parkinsons-disease/

AskBio presents 18-month Phase Ib trial results of AB-1005 ... These early findings are encouraging and show AB-1005 to be well tolerated in this study in patients with mild to moderate Parkinson's disease.

2. neurology.org neurology.org/doi/10.1212/WNL.0000000000206690

Phase 1b Safety and Preliminary Efficacy of Bilateral ... These preliminary findings suggest AAV2-GDNF is well tolerated in participants with PD, demonstrating general stability of the Mild Cohort and possible ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT01621581

AAV2-GDNF for Advanced Parkinson s Disease The gene transferred in this study, called AAV2-GDNF, may help produce GDNF to protect the damaged brain cells. Objectives: - To test the safety and ...

4. bayer.com bayer.com/en/us/news-stories/phase-ii-gene-therapy-trial-for-parkinsons-disease

First participants randomized in AskBio Phase II gene ... The objective of this randomized, double-blind, Phase II clinical trial is to evaluate the safety and efficacy of AB-1005 delivered to the putamen in adult ...

5. movementdisorders.onlinelibrary.wiley.com movementdisorders.onlinelibrary.wiley.com/doi/full/10.1002/mds.30193

Intraputaminal Delivery of Adeno‐Associated Virus Serotype 2 ... Bilateral intraputaminal AAV2-GDNF gene therapy was well tolerated and associated with numerical stability (mild cohort) and improvement (moderate cohort) in ...

6. bayer.com bayer.com/media/en-us/askbio-announces-completion-of-enrollment-in-phase-1-clinical-trial-of-ab-1005-gene-therapy-for-multiple-system-atrophy-parkinsonian-type-msa-p/

AskBio Announces Completion of Enrollment in Phase 1 ... Preliminary Efficacy of GDNF Gene Therapy (AAV2-GDNF; AB-1005) in Parkinson's Disease: 36-Month Follow-Up From a Phase 1b Study. Presented at ...