Human embryonic stem cells - from the bench to a clinical transplantation trial in retinal degeneration

We describe the road map of preclinical studies towards the development of human embryonic stem cells (hESCs)-derived retinal pigmented epithelial (RPE) cells (OpRegen) for transplantation therapy in dry age-related macular degeneration (dAMD), the leading untreatable cause of blindness in the western world.

The retinal degeneration in dAMD results from the loss of RPE cells. We describe the development of hESC-derived RPE, that when transplanted subretinally in pre-clinical studies, survive and integrate anatomically and provide functional rescue of the photoreceptors.

We describe interim results of an ongoing Phase I/IIa clinical transplantation study, conducted by Cell Cure Neurosciences Ltd. and Lineage Cell Therapeutics, Inc.,

in patients with advanced dry AMD (NCT02286089). We report accumulated safety and imaging data from first fifteen patients.

Subretinal clinical transplantation appears well tolerated to date and there have been no unexpected adverse events (AEs) or treatment-related systemic serious AEs. The most common AEs were the formation of mild epiretinal membranes. One instance of retinal detachment was reported. The event was not able to be assigned as related to treatment, procedure, or to the combination and the patient continued in the study following successful surgical repair. Findings on imaging suggest presence of transplanted cells in the subretinal space. Potentially positive structural and clinical changes observed in some of the patients will require additional follow-up over time.