VY-AADC Phase 1b and RESTORE-1

The research record

This is the project's file for this landmark, as written and checked. Sources are listed at the end; anything not yet confirmed is marked "Not yet verified".

Who

Voyager Therapeutics, with Neurocrine Biosciences as partner and then sponsor from 2019. Trade press named Mark Richardson as RESTORE-1's principal investigator.

What happened

AADC (the enzyme that turns levodopa into dopamine) falls as dopamine neurons die. VY-AADC is an AAV2 virus carrying the AADC gene, infused into the putamen under real-time MRI (landmark 253). The first human trials are in landmark 112; the 15-person Phase 1 (NCT01973543, three doses, completed Jan 2020) is the one reported there.

• Phase 1b (PD-1102, NCT03065192). 16 people, one dose (9.4×10^12 vector genomes), started May 2017, completed Aug 2021. No results were found.
• RESTORE-1 (NCT03562494). Randomised, double-blind, sham-surgery-controlled. It began in October 2018. It was designed with 1:1 randomisation and a main goal of "good ON time" (hours when symptoms are controlled without dyskinesia) at 12 months. The registry names the product VY-AADC02 (also NBIb-1817), up to 3.6×10^12 vector genomes. The registry now lists 14 participants, status Completed (Oct 2024), and a safety-only primary outcome.
• Halt. Screening was paused in April 2020 for COVID-19. In December 2020 the FDA put RESTORE-1 on clinical hold after the safety board asked for a dosing pause because of MRI abnormalities. On 2 Feb 2021 Neurocrine gave notice it would end the Parkinson's part of the deal (effective 2 Aug 2021), saying it was a portfolio decision. Three-year data from earlier cohorts, shown in September 2020, reported lower medication needs and no related serious adverse events; these are company data.

Why it moved us toward a cure

Honestly framed, this treats symptoms, not the disease. It was a sham-controlled test of a brain gene therapy aimed at dopamine production, and the hold stopped it before a clear answer appeared.

Outcome

Dead end for Parkinson's. No RESTORE-1 efficacy result was found. This is not a disease-modifying trial, so it is not added to the dead-ends table.

Sources

• ClinicalTrials.gov NCT01973543, NCT03065192, NCT03562494 (API checked 19 Oct 2026)
• NeurologyLive on the termination, Feb 2021
• Clinical Trials Arena on RESTORE-1 design
• Not yet verified: planned and actual RESTORE-1 enrolment (the registry shows 14; an earlier report said 42 planned); how many were dosed before the hold; the Phase 1b results; the COVID pause date (search summary of a Voyager release); the nature of the MRI abnormalities; Voyager's own releases (blocked).