RESTORE-1: first patient dosed with gene therapy in Parkinson’s trial

Written by Sharon Salt, Editor

Voyager Therapeutics (MA, USA) has announced that they have dosed the first patient in RESTORE-1, a Phase II, randomized, double-blind, placebo-controlled trial evaluating the safety and efficacy of VY-AADC for the treatment of Parkinson’s disease (PD) in patients with motor fluctuations that are refractory to medical management.
VY-AADC is an investigational gene therapy product designed to deliver the AADC gene directly into neurons of the putamen where dopamine receptors are located. This approach bypasses the substantia nigra neurons and is reported to enable the neurons of the putamen to produce the AADC enzyme to convert levodopa into dopamine.

By using this approach, VY-AADC has the potential to enhance the conversion of levodopa to dopamine and provide clinically meaningful improvements by restoring motor function in patients and improving symptoms following a single administration.

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“Patients with PD need new therapeutic options, especially as the disease progresses and there is less AADC enzyme in parts of the brain where it is needed to convert levodopa to dopamine,” commented Mark Richardson (University of Pittsburgh Medical Center, PA, USA), principal investigator in the RESTORE-1 trial.

The eligibility criteria for the Phase II RESTORE-1 trial includes individuals who have been diagnosed with PD for at least 4 years, are not responding adequately to oral medications and have at least 3 hours OFF time during the day, as measured by a validated self-reported patient diary. People who meet the eligibility criteria about will be randomized (1:1) to either a one-time administration of VY-AADC or placebo surgery.

The primary endpoint for RESTORE-1 includes an ON time without troublesome dyskinesia, or good ON time, as measured by a self-reported patient diary at 12 months. The secondary endpoints for the study include diary OFF time, other motor function, and quality-of-life measures.

Biomarker data will also include measurements of the coverage of the putamen targeted with VY-AADC and measurements of AADC enzyme expression and activity in the putamen (as measured by PET using fluorodopa F-18). The investigators also note that changes in patients’ daily doses of oral levodopa and related medications will also be recorded.