Gene Therapy for Parkinson's Disease

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

14 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the treatment AAV-GAD for Parkinson's Disease?

Gene therapy using adeno-associated virus (AAV) vectors has shown promise in treating Parkinson's Disease by delivering genes that help produce important brain chemicals like dopamine and GABA, which can improve motor functions. In one study, patients showed a 46% improvement in motor functions after receiving a similar AAV-based gene therapy, indicating potential effectiveness. ^{1 2 3 4 5}

Is gene therapy using AAV-GAD safe for humans?

Gene therapy using AAV-GAD has been tested in humans for Parkinson's disease, and while it shows promise, there have been reports of severe adverse reactions, including death, in some AAV gene therapy trials. This highlights the need for careful safety monitoring. ^{1 6 7 8 9}

How is the treatment AAV-GAD unique for Parkinson's disease?

AAV-GAD is a gene therapy that uses a virus to deliver a gene into the brain, which helps produce GABA, a chemical that calms overactive brain areas in Parkinson's disease. This approach is different from traditional treatments that mainly focus on replacing dopamine, the brain chemical that is low in Parkinson's patients. ^{1 3 8 9 10}

What is the purpose of this trial?

The objective of this study is to evaluate the long-term safety of AAV-GAD delivered bilaterally to the subthalamic nuclei (STN) in participants with Parkinson's disease.

Eligibility Criteria

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

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

Treatment Details

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).

Participant Groups

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 a period of 60 months after vector administration.

Who Is Running the Clinical Trial?

MeiraGTx, LLC

Lead Sponsor

Trials

6

Recruited

310+

Findings from Research

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Pre-existing immunity to adeno-associated virus (AAV)2 limits transgene expression following intracerebral AAV2-based gene delivery in a 6-hydroxydopamine model of Parkinson's disease. [2014]

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

A phase I study of aromatic L-amino acid decarboxylase gene therapy for Parkinson's disease. [2021]

3. England pubmed.ncbi.nlm.nih.gov

A next step in adeno-associated virus-mediated gene therapy for neurological diseases: regulation and targeting. [2021]

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

Gene therapy for Parkinson's disease: where are we now and where are we going? [2012]

5. England pubmed.ncbi.nlm.nih.gov

Gene therapy for Parkinson's disease using recombinant adeno-associated viral vectors. [2019]

6. England 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. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Safety and tolerability of gene therapy with an adeno-associated virus (AAV) borne GAD gene for Parkinson's disease: an open label, phase I trial. [2022]

8. United States 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. [2012]

9. Austria pubmed.ncbi.nlm.nih.gov

AAV-GAD gene for rat models of neuropathic pain and Parkinson's disease. [2019]

10. Japan pubmed.ncbi.nlm.nih.gov

[Gene therapy for Parkinson's disease]. [2019]