Introduction: DA01 is an allogeneic hPSC-derived dopaminergic neuron cell therapy in development for Parkinson’s disease (PD). A Phase I clinical trial (NCT04802733) to assess the safety and tolerability of bilateral implantation of DA01 into the putamen, including a two-dose escalation scheme, has completed enrollment of all 12 subjects.
Methods: hPSC-derived dopaminergic neuron progenitors were derived from human pluripotent stem cells using a robust differentiation protocol followed by cryopreservation. Extensive molecular profiling confirmed midbrain dopaminergic neuronal progenitor identity and IND-enabling testing demonstrated safety and lack of toxicity and tumorigenicity of the cell product. Efficacy studies in a rat Parkinson model demonstrated consistent reversal of behavioral deficits. In the Phase I study, 12 subjects received bilateral stereotactic implantation of DA01 cells along 3 trajectories targeting the post-commissural putamen. Patients receive immunosuppression for one year and are followed closely with clinical assessments, PD clinical rating scores, MRI and 18F-Dopa PET scans.
Results: Safety data from the low-dose cohort supported the prospectively planned escalation to the high dose. All twelve planned subjects (mean age: 65.8 years (range: 57-76); 9 male, 3 female) have now undergone surgical delivery of DA01 and are currently being monitored per trial protocol. Surgical strategies will be presented and discussed.
Conclusion : This is a first in human clinical trial of off-the-shelf hPSC-derived dopaminergic neuron progenitors. The early patient experience from this study supports the feasibility of delivering DA01 stereotactically to the bilateral putamen in subjects with PD.
