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Safety and tolerability of RPESC-RPE transplantation in patients with dry age-related macular degeneration: Low-dose clinical outcomes

09/2025

Journal Article

Authors:
Rao, R. C.; Arduini, B. L.; Borden, S.; Sareen, D.; Svendsen, C.; Lee, P.; Ryan, C.; Kodati, S.; Nyaiburi, C.; Wolsieffer, K.; Oh, E.; Park, S.; Ford, G.; Dionne, K.; Temple, S.; Stern, J.

Journal:
Cell Stem Cell

PMID:
40961946

URL:
https://www.ncbi.nlm.nih.gov/pubmed/40961946

DOI:
10.1016/j.stem.2025.08.012

Keywords:
adult stem cell cell therapy clinical trial geographic atrophy macular degeneration retina retinal pigment epithelium vision

Abstract:
Retinal pigment epithelium (RPE) cell atrophy in dry age-related macular degeneration (AMD) compromises photoreceptor cell function, leading to vision loss. Stem cell-based RPE replacement therapy aims to reverse disease progression and restore vision. RPESC-RPE-4W, a post-mitotic adult RPE stem cell-derived RPE (RPESC-RPE) progenitor cell product, exhibits consistent safety and efficacy in preclinical studies. The first-in-human clinical trial of RPESC-RPE-4W completed low-dose cohort 1 interventions (NCT04627428). Six subjects received a subretinal suspension of 50,000 RPESC-RPE-4W cells. No significant inflammation, tumor, or product-related serious adverse events were observed. Best-corrected visual acuity in the three worse-seeing group A subjects improved by an average of +21.67 letters from baseline at 12 months. Three better-seeing group B subjects improved by an average of +3.0 letters at 6 months. The positive safety and tolerability outcomes for low-dose cohort 1 enabled dose escalation to mid-dose RPESC-RPE-4W therapy for dry AMD.

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