Phase 2 Trial of Gene Therapy, VY-AADC02, for Advanced Parkinson’s Enrolling in US

A Phase 2 clinical trial testing the safety and effectiveness of the gene therapy VY-AADC02 in people with advanced Parkinson’s disease is recruiting patients at select sites across the U.S., according to a release by one such site.

Hackensack University Medical Center is among the 17 institutions across the U.S. enrolling up to 40 patients ages 40 to 75 , all diagnosed four or more years ago, for the double-blinded RESTORE-1 (NCT03562494) study.

Eligible patients must be experiencing unpredictable motor fluctuations despite use of treatments, and are not planning to undergo neurological surgeries such as deep brain stimulation or take new dopaminergic formulations during the study.

An eligibility questionnaire is available on the trial’s website.  Contact information for participating sites can also be found here.

RESTORE-1 will assess the safety and efficacy of VY-AADC02, delivered in a surgical procedure monitored in real-time via magnetic resonance imaging. Treatment with the gene therapy will be compared to a “sham” procedure, with half of the enrolled patients randomly assigned to treatment.

Trial participants must be able to make at least 21 visits to their clinical site, spread over two months of pre-treatment assessments and 12 months of follow-up.

Parkinson’s is characterized by progressive loss of dopamine-producing nerve cells and lower levels of the L-amino acid decarboxylase (AADC) enzyme, which mediates the conversion of levodopa into dopamine.

VY-AADC02 is a gene therapy developed by Neurocrine Biosciences and Voyager Therapeutics. It uses a modified, harmless viral vector to deliver the AADC gene directly into the putamen, a brain region associated with motor control and filled with dopamine receptors. This gene carries the information for the production of the AADC enzyme.

Latest results of the Phase 1 PD-1102 clinical trial (NCT03065192) found that treatment with VY-AAD01 — a precursor of VY-AADC02 — into the striatum (a brain area that includes the putamen) improved motor function and reduced the need for antiparkinsonian medications by 28% in patients with advanced Parkinson’s.

Other benefits included an 85% increase in AADC activity in the putamen, and improvements in a quality of life score.

A Phase 1b trial in that precursor therapy, called PD-1101 (NCT01973543), has shown dose-dependent improvements in motor function and quality of life, as well as a reduced need for antiparkinsonian medications.

These two studies use different surgical approaches. In PD-1101, the gene therapy was injected through the top of the head (called a frontal approach), and in PD-1102 it was delivered through the back (a posterior approach), which is intended to both reduce the infusion time and increase the therapy’s coverage of its targeted brain area.

Participants who complete trials of either VY-AADC01 or VY-AADC02 will have the possibility of joining a long-term extension study (NCT03733496), expected to conclude in August 2026.