Imaging Outcomes of a Dopaminergic Neuronal Cell Therapy for Parkinson’s Disease: 18-month Results from a Phase 1 Study of Bemdaneprocel
Claire Henchcliffe1, Yilong Ma2, Harini Sarva3, Andres Lozano4, Alfonso Fasano5, Suneil Kalia6, Kenny Kwok Hei Yu7, Cameron Brennan7, Nicki Jennings8, Whitney stemple9, Nauman Abid9, Marcus Yountz9, Ahmed Enayetallah9, Antoine Lampron9, Viviane Tabar7, David Eidelberg2
1University of California, Irvine, 2Feinstein Institute for Medical Research, 3Weill Cornell Medical Center, 4Toronto Western Hosp, 5Toronto Western Hospital - U of Toronto, 6University of Toronto, 7Memorial Sloan Kettering Cancer Center, 8BlueRock Therapeutics LP, 9BlueRock Therapeutics
Objective:
Evaluate [18F]-fluorodopa (18F-DOPA) positron emission tomography (PET) signal 18 months post transplantation (6 months after cessation of immunosuppression) in 12 participants who received intraputamenal transplants of bemdaneprocel.
Background:
Bemdaneprocel is an investigational cellular therapy composed of pluripotent stem cell–derived dopaminergic neuron precursor cells under development for the treatment of Parkinson’s disease. At 1 year post transplantation, bemdaneprocel was generally safe and well tolerated in 12 participants. Relative to baseline, increases in putamen 18F-DOPA PET signal indicated successful transplantation and graft survival in the target region.
Design/Methods:
In this open-label, 24-month, non-controlled study, 12 participants received 1 of 2 doses of bemdaneprocel to the post-commissural putamen bilaterally and a 1-year immunosuppression regimen. Changes from baseline in 18F-DOPA uptake were measured by striatal-to-occipital ratio for each participant within regions of interest defined by voxel-based brain mapping analysis at a group level. Participants were also assessed for morphologic changes by magnetic resonance imaging (MRI) before and after surgery and at multiple time points through year 1.
Results:
Compared with baseline, group-level analysis (N=12) of 18F-DOPA uptake at 1 year post transplantation revealed clusters of increased signal within the striatal hypothesis testing space (p<0.05). Whereas increases in 18F-DOPA uptake were discerned along surgical tracts through the putamen (p<0.005), caudate signal declined over the same time interval (p<0.01). MRI demonstrated no changes in target volume over the 1 year post transplantation.
Conclusions:
Increased post-transplantation 18F-DOPA PET signal along posterior putamen surgical trajectories is consistent with survival of bemdaneprocel grafts at 1 year. Concurrent MRI assessments of target volume did not reveal evidence of cell overgrowth during the same time period. Additional results will be presented, including imaging data acquired 18 months after transplantation (6 months after the cessation of immunosuppression).