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Virus Therapy

Gene Therapy for AADC Deficiency (AADC Trial)

Phase 1

Recruiting

Led By Nalin Gupta, MD, PhD

Research Sponsored by Krystof Bankiewicz

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Age 24 months and older

Brain MRI does not show any conditions or malformations that are clinically significant with respect to risks for stereotactic brain surgery

Must not have

Presence of other significant medical or neurological conditions that would create an unacceptable operative or anesthetic risk (including congenital heart disease, respiratory disease with home oxygen requirement, history of serious anesthesia complications during previous elective procedures, history of cardiorespiratory arrest), liver or renal failure, malignancy, or HIV positive

Coagulopathy, or need for ongoing anticoagulant therapy

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a gene therapy for children with AADC deficiency, a disease that affects the brain's ability to produce certain neurotransmitters. The therapy involves injecting a virus carrying the healthy gene into the brain.

Who is the study for?

This trial is for children aged 4 and older with AADC deficiency, a rare metabolic disorder. They must have a stable medication regimen, confirmed diagnosis through specific tests, be unable to walk independently, and have no recent changes in medications. Children who haven't benefited from standard treatments may qualify. Those with certain medical conditions or previous brain surgery are excluded.

What is being tested?

The study is testing the safety and effectiveness of delivering the gene therapy drug AAV2-hAADC directly into parts of the brain responsible for movement control in kids with AADC deficiency. The goal is to see if this treatment can improve symptoms related to this genetic condition.

What are the potential side effects?

While not explicitly listed here, potential side effects could include reactions at the injection site in the brain, immune responses to the viral vector used for gene delivery (AAV2), and any complications arising from neurosurgical procedures.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am at least 24 months old.

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My brain MRI is clear for stereotactic surgery.

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I couldn't walk on my own without help by 18 months old.

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My skull is fully formed for a specific head frame placement.

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I have been diagnosed with AADC deficiency based on specific test results.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I do not have major health issues that would make surgery or anesthesia very risky.

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I have a blood clotting disorder or need continuous blood thinner treatment.

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I have not taken any experimental drugs in the last 60 days.

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I have had precise brain surgery before.

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I cannot be sedated for surgery or certain imaging tests.

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I show signs of an active adenovirus or herpes virus infection.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 2 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Operative Surgical Procedures

CSF neurotransmitter metabolite concentrations

Secondary study objectives

Fluorodopa PET scan

Gross Motor Function Measure

Symptom Diary created by PI

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Single treatment armExperimental Treatment1 Intervention

Single-stage dose-escalation, open-label safety study of AAV2-hAADC delivered by image-guided convection-enhanced delivery bilaterally into the substantia nigra pars compacta and the ventral tegmental area of pediatric patients with AADC deficiency. Primary aim is to determine the dose for future studies based on safety, biomarkers of pharmacological activity of AADC and clinical outcomes. Cohort 1 (3 subjects) will receive a single low dose of AAV2 hAADC. The total AAV2-hAADC dose will be infused via MR guided infusion into 4 sites in both the left and right SNc and VTA. Dose intervals will be 90 days between the first 3 subjects. Cohort 2 dose (4 subjects) will be determined by Cohort 1 results. Following Cohort 2, Cohort 3/4 will be dose and divided divided by age. Cohorts 3/4 will receive the same dose by MR guided infusion to 1-2 sites bilaterally in-between the SNc and VTA. Cohort 5 (24-47mo old) will have same vector concentration and lower volume of infusion than Cohorts 3/4

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

AAV2-hAADC

2016

Completed Phase 2

~20

0 / 11Eligibility criteria met