Gene Therapy for Parkinson's Disease

(PDCS-01 Trial)

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Krzysztof Bankiewicz

Must be taking: Dopaminergic therapy

Must not be taking: Antipsychotics, Apomorphine, Levodopa infusion

Disqualifiers: Cognitive impairment, Psychosis, Severe depression, Stroke, others

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

Compensation: Varies

Number of Visits: 1

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a new gene therapy is safe and beneficial for people with Parkinson's Disease. The treatment uses a modified virus to boost dopamine levels in the brain, potentially improving movement and other symptoms. Participants will receive one of two doses to identify the most effective option. This trial targets individuals diagnosed with Parkinson's for over three years, experiencing significant movement issues, and who noticed symptoms before age 50. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects on people.

Will I have to stop taking my current medications?

The trial requires that you have a stable regimen of Parkinson's medications for at least 4 weeks before the screening. However, you may need to temporarily stop any anticoagulation or antiplatelet therapy for at least 2 weeks during the surgery period. Ongoing treatments like antipsychotic medications, apomorphine, or levodopa infusion therapy might interfere with the study and may need to be stopped.

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

Research has shown that the gene therapy AAV2-hAADC is safe for people with Parkinson's Disease. Studies have found that patients generally tolerate this treatment well. For instance, one study noted that the treatment was safe, with effects lasting at least four years. In another study, patients with advanced Parkinson's who received this therapy did not experience any major safety issues. These findings suggest that AAV2-hAADC could be a promising option for boosting dopamine levels in the brain, which is important for managing Parkinson's symptoms. ^{1 2 3 4 5}

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

Most treatments for Parkinson's disease, like levodopa and dopamine agonists, work by boosting dopamine levels in the brain to manage symptoms. But AAV2-hAADC works differently, using gene therapy to deliver a key enzyme called AADC directly to brain cells. This enzyme helps convert levodopa into dopamine more efficiently, potentially leading to better symptom control. Researchers are excited because this could mean longer-lasting effects and fewer side effects compared to current treatments. Additionally, the use of a viral vector to deliver the gene directly to the brain represents a cutting-edge approach in treating neurological disorders.

What evidence suggests that this gene therapy might be an effective treatment for Parkinson's Disease?

Research shows that AAV2-hAADC gene therapy might help increase dopamine levels in the brain, which is crucial for people with Parkinson's Disease. This therapy uses a virus to deliver a gene that aids in converting levodopa into dopamine. Studies have found that this method is safe and remains effective for at least four years. In children with a condition similar to the target of this therapy, gene delivery improved symptoms and movement. Additionally, the treatment has been well-tolerated in people with advanced Parkinson's Disease, with no major safety issues reported. This trial will test two different doses of AAV2-hAADC. These findings suggest that AAV2-hAADC could help improve symptoms by boosting dopamine production. ^{1 3 5 6 7}

Are You a Good Fit for This Trial?

This trial is for individuals with Parkinson's Disease. Participants should have a confirmed diagnosis and may be experiencing symptoms that aren't fully managed by current treatments. Specific eligibility details are not provided, but typically participants must be in stable health aside from their Parkinson's.

Inclusion Criteria

UPDRS Part III (total motor) score ≥25 in the clinically defined OFF state

My Parkinson's medication has been stable for at least 4 weeks.

My Parkinson's symptoms have been stable for at least 4 weeks.

Exclusion Criteria

Clinically significant cognitive impairment

Presence or history of psychosis, severe depression, or active suicidal ideation

Presence of impulse control disorder or substance use disorder within 2 years of screening evaluation

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

AAV2-hAADC gene therapy is administered via MRI-guided convective infusion into the putamen and caudate

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness, including adverse events, MRI findings, and physical exams

3 years

What Are the Treatments Tested in This Trial?

Interventions

• AAV2-hAADC

Trial Overview The study tests AAV2-hAADC gene therapy, which aims to increase dopamine levels in the brain by delivering a modified virus carrying genetic code to produce more of the enzyme AADC in areas affected by Parkinson's.

How Is the Trial Designed?

Group I: Dose 2 (High Dose) Experimental Treatment 1 Intervention

Total Dose (vg): up to 1.3E13

Group II: Dose 1 (Low Dose) Experimental Treatment 1 Intervention

Total Dose (vg): up to 4.2E12

Who Is Running the Clinical Trial?

Krzysztof Bankiewicz

Lead Sponsor

Trials

1

Recruited

40+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4530392/

Long-Term Evaluation of a Phase 1 Study of AADC Gene ... This study showed that AAV2-hAADC treatment was safe and that AADC gene expression was maintained at least 4 years after administration of therapy.

2. nature.com nature.com/articles/s41467-021-24524-8

Gene therapy for aromatic L-amino acid decarboxylase ... Midbrain gene delivery in children with AADC deficiency is feasible and safe, and leads to clinical improvements in symptoms and motor function.

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2352464217301256

Efficacy and safety of AAV2 gene therapy in children with ... Aromatic l-amino acid decarboxylase (AADC) deficiency is an inherited disease that causes depletion of neurotransmitters and severe motor dysfunction in ...

4. neurology.org neurology.org/doi/10.1212/WNL.0000000000012952

Safety of AADC Gene Therapy for Moderately Advanced ... This study provides Class IV evidence that, in patients with moderately advanced PD and motor fluctuations, putaminal infusion of VY-AADC01 is well tolerated ...

5. journals.lww.com journals.lww.com/neurosurgery/fulltext/2012/10000/gene_therapy_for_aromatic_l_amino_acid.4.aspx

Gene Therapy for Aromatic L-Amino Acid Decarboxylase... This first gene therapy trial for AADC deficiency adds to the established safety profile of intracerebral AAV2-mediated gene therapy.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT07267065

AAV2-hAADC for Parkinson's Disease (PDCS-01) This study is looking at whether a gene therapy called AAV2-hAADC is safe and may help people with Parkinson's Disease.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8726573/

Safety of AADC Gene Therapy for Moderately Advanced ... This study provides Class IV evidence that, in patients with moderately advanced PD and motor fluctuations, putaminal infusion of VY-AADC01 is well tolerated ...