Objective: Evaluate the safety of VY-AADC01, an AAV2 gene therapy vector with human aromatic L-amino acid decarboxylase (AADC) administered bilaterally to the putamen using intraoperative MRI.

Background: The progressive loss of AADC, which converts levodopa to dopamine, may account for the reduced efficacy over time of levodopa therapy in people with Parkinson’s disease (PD).

Methods: Three cohorts of 5 subjects each, with PD duration of at least 5 years and motor fluctuations despite optimal medical treatment, received bilateral infusions of VY-AADC01 admixed with gadoteridol to facilitate the intraoperative MRI visualization of putaminal delivery. Subjects in Cohort 1 received up to 450 μl/putamen at a concentration of 8.3×1011 vg/ml, Cohort 2 received up to 900 μl/putamen at 8.3×1011 vg/ml, and Cohort 3 received up to 900 μl/putamen at 2.6×1012 vg/ml. AADC activity was assessed using 18F-dopa PET at baseline and month 6.

Results: Treatment was well tolerated with no vector related SAEs; one post-procedure pulmonary embolus resolved with anticoagulation. Average coverage of the putamen was 21%, 35%, and 42% for Cohorts 1, 2, and 3, respectively. By 6 months, dose dependent improvements were seen in diary measures including ON-time without troublesome dyskinesia and OFF-time [figure1] which allowed reductions of PD medications [figure2]. 18F-dopa PET imaging showed increased AADC activity of 13%, 56%, and 79%, respectively [figure3]. UPDRS motor and PDQ-39 scores showed similar dose-dependent trends. Updated long-term data will be reported.

Conclusions: Conclusion: VY-AADC01 administered to the putamen using intraoperative MRI is well-tolerated. Early signals from this Phase 1b trial show dose-dependent gene expression and potential clinical efficacy

« Back to 2018 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/vy-aadc01-gene-therapy-in-parkinsons-disease-interim-results-of-the-on-going-phase-1b-pd-1101-trial/