A phase I clinical trial of human embryonic stem cell‐derived retinal pigment epithelial cells for early‐stage Stargardt macular degeneration: 5‐years' follow‐up

Abstract

Objectives To evaluate the long‐term biosafety and efficacy of transplantation of human embryonic stem cells‐derived retinal pigment epithelial (hESC‐RPE) cells in early‐stage of Stargardt macular degeneration (STGD1). Materials and methods Seven patients participated in this prospective clinical study, where they underwent a single subretinal transplantation of 1 × 105 hESC‐RPE cells in one eye, whereas the fellow eye served as control. These patients were reassessed for a 60‐month follow‐up through systemic and ophthalmic examinations. Results None of the patients experienced adverse reactions systemically or locally, except for two who had transiently high intraocular pressure post‐operation. Functional assessments demonstrated that all of the seven operated eyes had transiently increased or stable visual function 1‐4 months after transplantation. At the last follow‐up visit, two of the seven eyes showed visual function loss than the baseline; however, one of them showed a stable visual acuity when compared with the change of fellow eye. Obvious small high reflective foci in the RPE layer were displayed after the transplantation, and maintained until the last visit. Interestingly, three categories of patients who were classified based on autofluorescence, exhibited distinctive patterns of morphological and functional change. Conclusions Subretinal transplantation of hESC‐RPE in early‐stage STGD1 is safe and tolerated in the long term. Further investigation is needed for choosing proper subjects according to the multi‐model image and function assessments.

Human Stem Cell Transplantation for Retinal Degenerative Diseases: Where Are We Now?

“…Two of the clinical trials were not related to retinal treatments and were excluded from the study. A summary of the conclusions of the 10 papers containing results from clinical trials and published between 2014 and 2021 [10][11][12][13][14][15][16][17][18][19] is presented in Table 1. Retinitis pigmentosa.…”

“…A phase I clinical trial of human embryonic stem cell-derived retinal pigment epithelial cells for early-stage Stargardt macular degeneration: 5-years' follow-up (NCT02749734) [19] Early-stage of Stargardt macular degeneration (STGD1).…”

“…Although 36% of the trials were completed, only two of them had posted results. Seven articles from our PubMed search had published results linked with 8 of the clinical trials [10,11,[13][14][15][16]19].…”

Where Are We with RPE Replacement Therapy? A Translational Review from the Ophthalmologist Perspective

“…Binder et al enrolled in their trial 53 patients, of which 39 patients underwent RPE cells transplantation along with membranectomy while 14 patients underwent membranectomy only as a control group [ 28 ]. RPE cells were harvested subretinally from the nasal side of the optic disc, centrifugated and then injected into the subretinal space.…”

“…Li et al described the outcomes of 7 patients with Stargardt’s disease, aged 19–27 years, who were treated in a phase 1 clinical trial [ 28 ]. For each participant, the poorer-seeing eye was selected for intervention; the better-seeing contralateral eye served as an untreated control.…”