Gene Therapy for Parkinson's Disease

Not currently recruiting at 5 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: MeiraGTx, LLC

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the safety of a gene therapy called AAV-GAD for people with Parkinson's disease. The therapy targets a specific brain area that controls movement. The trial includes two groups: one receives the gene therapy, while the other undergoes a different procedure and is closely monitored. Participants must have taken part in a previous related study to join. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Do I need to stop taking my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications.

Is there any evidence suggesting that AAV-GAD is likely to be safe for humans?

Research has shown that AAV-GAD, a gene therapy for Parkinson's disease, was safe and well-tolerated in earlier studies. Patients who received AAV-GAD experienced no serious side effects. This finding suggests the treatment is generally safe. Additionally, some patients demonstrated improved movement abilities after receiving the therapy. These results build confidence in the safety of AAV-GAD for potential trial participants. ^{1 2 3 4 5}

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

Researchers are excited about AAV-GAD for Parkinson's disease because it offers a new way to tackle this challenging condition. Unlike standard treatments like Levodopa and dopamine agonists, which primarily aim to replenish or mimic dopamine, AAV-GAD uses gene therapy to increase the production of GABA, a neurotransmitter that helps regulate brain activity. This approach targets the root of abnormal brain signaling, potentially slowing or altering the progression of the disease rather than just managing symptoms. By delivering therapeutic genes directly into the brain, AAV-GAD could offer longer-lasting effects and a new hope for people with Parkinson’s.

What evidence suggests that AAV-GAD might be an effective treatment for Parkinson's disease?

Research has shown that AAV-GAD gene therapy might help treat Parkinson's disease. In this trial, participants in the active treatment group will receive AAV-GAD. Studies have found that this therapy greatly improves movement, with patients showing an 18-point improvement in their movement scores. The benefits of this treatment lasted for at least a year. Additionally, AAV-GAD has proven safe, with no serious side effects directly linked to it. Overall, these findings suggest that AAV-GAD could provide lasting improvements for people with Parkinson's disease. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

This trial is for participants who were previously enrolled in Study MGT-GAD-025. There are no additional exclusion criteria, meaning that past participants of the mentioned study can join regardless of other conditions.

Inclusion Criteria

Previously enrolled in Study MGT-GAD-025

Exclusion Criteria

Not applicable.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Active Treatment

Participants who received sham surgery will transition to an active treatment schedule including open-label bilateral treatment

6 months

Long-term Follow-up

Participants are monitored for long-term safety of AAV-GAD delivered bilaterally to the subthalamic nuclei

54-60 months

What Are the Treatments Tested in This Trial?

Interventions

• AAV-GAD

Trial Overview

The trial is studying the long-term safety of a gene therapy called AAV-GAD, which was given to patients with Parkinson's disease by injecting it into a part of the brain known as the subthalamic nuclei (STN).

How Is the Trial Designed?

Group I: Active treatment group Experimental Treatment 1 Intervention

Participants who were randomized to sham surgery in Study MGT-GAD-025 will transition to an active treatment schedule, including open-label bilateral treatment, upon confirmation of continued eligibility. Upon completion of the treatment period, participants will enter the long-term follow-up schedule to complete a total of 60 months of follow-up.

Group II: Follow-up group Active Control 1 Intervention

Participants who were randomized to immediate treatment in Study MGT-GAD-025 will transition directly to a long-term follow-up schedule to complete an additional 54 months of follow-up. All study participants are to be followed for 60 months after vector administration.

Who Is Running the Clinical Trial?

MeiraGTx, LLC

Lead Sponsor

Trials

6

Recruited

310+

Published Research Related to This Trial

Gene therapy for Parkinson's disease involves delivering genes that can produce dopamine or protect neurons, using recombinant adeno-associated viral (rAAV) vectors that are effective and safe for long-term use in the brain.

These rAAV vectors have minimal inflammatory responses and can be monitored using imaging techniques, highlighting their potential for safe clinical applications as researchers work on improving transgene expression regulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gene therapy for Parkinson's disease using recombinant adeno-associated viral vectors. Muramatsu, S., Tsukada, H., Nakano, I., et al.[2019]

The phase I trial involving 10 patients with Parkinson's disease confirmed that the putaminal convection-enhanced delivery (CED) of the AAV2-hAADC gene therapy was accurately targeted, as shown by MRI imaging that revealed T2 hyperintensity around the cannula tracts shortly after treatment.

The correlation between MRI findings and PET uptake suggests that T2-weighted MRI can effectively visualize the distribution of the hAADC gene therapy, which is crucial for optimizing future trials and ensuring effective treatment delivery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Qualitative imaging of adeno-associated virus serotype 2-human aromatic L-amino acid decarboxylase gene therapy in a phase I study for the treatment of Parkinson disease. Valles, F., Fiandaca, MS., Eberling, JL., et al.[2012]

A systematic review of adeno-associated virus (AAV) gene therapies highlights their potential efficacy in treating previously untreatable neurological conditions, with an increasing number of clinical trials underway.

However, there are significant safety concerns, including reports of severe adverse reactions and even deaths, emphasizing the need for unified reporting of these events to enhance treatment safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review of adeno-associated virus gene therapies in neurology: the need for consistent safety monitoring of a promising treatment. Horton, RH., Saade, D., Markati, T., et al.[2022]

Citations

1.

investors.meiragtx.com

investors.meiragtx.com/news-releases/news-release-details/meiragtx-announces-positive-data-randomized-sham-controlled

MeiraGTx Announces Positive Data from Randomized, Sham ...

Top-line data summary: AAV-GAD was safe and well tolerated, with no serious adverse events (SAEs) related to AAV-GAD treatment. · About AAV-GAD.

2.

neurologylive.com

neurologylive.com/view/gad-related-parkinson-gene-therapy-aav-gad-demonstrates-efficacy-topline-findings

GAD-Related Parkinson Gene Therapy AAV ...

High-dose AAV-GAD therapy significantly improved motor function in Parkinson's patients, with an 18-point UPDRS Part 3 score improvement. · The ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC5374069/

Long-term follow-up of a randomized AAV2-GAD gene ...

These findings show that clinical benefits after gene therapy with STN AAV2-GAD in PD patients persist at 12 months. TRIAL REGISTRATION.

4.

medicalsciencepulse.com

medicalsciencepulse.com/article/162849/en

Parkinson's disease gene therapy: a comparative ...

VY-AADC01, AAV-GAD, and CERE-120 were found to be safe and potentially effective in the treatment of PD, while ProSavin demonstrated ...

5.

clinicaltrials.gov

clinicaltrials.gov/study/NCT00643890?term=AREA%5BConditionSearch%5D(Parkinson)%20AND%20AREA%5BBasicSearch%5D(%22gene%20therapy%22%20OR%20%22gene%20transfer%22%20OR%20%22virus%20delivery%22)&rank=8

NCT00643890 | Study of AAV-GAD Gene Transfer Into the ...

The purpose of this study is to determine the safety and efficacy of AAV-GAD gene transfer into the subthalamic nucleus (STN) region of the brain. This study ...