Effect of Human Central Nervous System Stem Cell Subretinal Transplantation on Progression of Geographic Atrophy Secondary to Non Neovascular Age-Related Macular Degeneration

Background: The safety and efficacy of subretinally transplanted human central nervous system stem cells (HuCNS-SCR) in subjects with geographic atrophy (GA). Methods: Twenty-two eyes of 11 subjects with bilateral GA due to age-related macular degeneration (AMD) were enrolled in this IRB-approved, multicenter, prospective Phase I/II open-label clinical trial. For each subject, the eye with the worst best-corrected visual acuity was selected for treatment and considered the study eye; the fellow eye was treated as a control for this analysis. A total of 0·25 X 106 or 1·0 X 106 HuCNS-SC cells were directly infused into the subretinal space, superotemporal to the fovea near the junctional zone outside the area of GA. Subjects were followed for 12 months and the GA was monitored with fundus autofluorescence (FAF) imaging. Total GA area in both eyes was measured at baseline and month 12 by certified graders and sectoral (clock hour)/directional GA progression rates with respect to the foveal center were computed, and compared between study and control eyes. Findings: Although there was a numerical difference and trend, no statistically significant difference was observed in the overall 12 month enlargement in GA area between study and fellow eyes (1·07 ± 0·84 vs. 2·08 ± 1·97 mm2, P=0·08). However, the month 12 sectoral/directional GA growth rate for the superotemporal region (i.e. toward the location of HuCNS-SC transplantation) showed a significantly slower progression rate in study eyes compared to the same region in fellow eyes (0·06 ± 0·11 vs. 0·21 ± 0·13 mm2, P=0·03). The progression rate in the superotemporal quadrant of the study eye was also significantly slower than in the other three quadrants of the study eye combined (P=0·003). Interpretation: In this Phase I/II trial, HuCNS-SC transplantation was well tolerated and appeared to be associated with slower expansion of the GA lesion in the transplanted quadrant. Trial Registration: NCT01632527. Funding Statement: The clinical study was supported in full by the original trial sponsor, StemCells, Inc. Declaration of Interests: Financial disclosure: Dr. Sadda receives research support from Carl Zeiss, Meditec, Optos, Genentech, and Allergan. He has served as a consultant for Genentech, Allergan, Alcon, Novartis, and Roche. Dr. Birch receives research support from Nightstar, Allergan, AGTC, 4D Molecular Therapeutics, and ProQR Therapeutics. He has served as a consultant for Nightstar, AGTC, Nacuity Pharmaceuticals, Editas Medicine, Acucela, Foundation Fighting Blindness, and ProQR Therapeutics. All other authors declare no conflicts of interest. Ethics Approval Statement: All study procedures were approved by the institutional review boards (IRBs) of the participating clinical centers, and the research adhered to the tenets set forth in the Declaration of Helsinki. Informed consent was obtained from all subjects after explanation of the study procedures and the expected risks and benefits.