Summary: A phase 1/2a clinical trial indicates that stem cell therapy may partially restore vision in people with advanced dry age-related macular degeneration (AMD), a condition that currently has no cure. Researchers transplanted retinal pigment epithelial stem cell–derived RPE cells, sourced from adult postmortem eye-bank tissue, into patients’ eyes and observed both a favorable safety profile and notable visual improvements in the lowest-dose group.
The treatment demonstrated safety in early testing and produced unexpected gains in visual acuity: some participants in the low-dose cohort could read substantially more letters on a standard eye chart one year after surgery. These early results represent a promising step toward regenerative approaches for a leading cause of vision loss.
Key facts
- Stem cell source: Retinal pigment epithelial cells derived from adult eye‑bank tissue, processed into RPESC‑RPE progenitor cells.
- Safety profile: No significant inflammation, tumor formation, or product-related serious adverse events were observed in the low‑dose cohort.
- Vision improvement: In the low‑dose group, the most affected eyes improved by an average of about 21 letters on a visual acuity chart at 12 months.
Source: University of Michigan
Background: In the United States, age‑related macular degeneration is a leading cause of irreversible central vision loss in adults aged 60 and older. The disease affects the macula, the central region of the retina responsible for high‑resolution, color, and detail vision. While peripheral vision typically remains intact, loss of macular function substantially reduces the ability to read, recognize faces, and perform detailed tasks.
About 20 million adults in the U.S. live with some form of AMD. There are two primary forms of macular degeneration: dry and wet. More than 90% of diagnosed cases are the dry form, which results from dysfunction and eventual loss of the retinal pigment epithelium (RPE). In early stages, RPE cells function poorly; in late stages, these cells atrophy and do not regenerate, causing progressive central vision loss as multiple central retinal areas lose viable RPE support.
Current therapies for AMD can slow progression, especially for the wet form, but there are presently no widely available treatments that reliably restore lost RPE cells or reverse vision loss in advanced dry AMD. Stem cell–based strategies aim to replace damaged RPE and rescue photoreceptor function, offering a potential regenerative solution.
This first‑in‑human trial evaluated RPESC‑RPE‑4W, a post‑mitotic adult RPE stem cell‑derived progenitor product developed for RPE replacement. In the low‑dose cohort (clinical trial NCT04627428), six patients received a subretinal injection of 50,000 RPESC‑RPE‑4W cells via a surgical procedure. The primary goal of this early‑phase study was to assess safety and tolerability.
Across these six participants, investigators observed no significant inflammation, tumor development, or other serious product‑related adverse events over the follow‑up period. Functionally, patients showed differential visual responses: the three subjects with worse baseline vision (group A) improved substantially, gaining an average of +21.67 letters at 12 months. The three better‑seeing subjects (group B) experienced smaller average gains (+3.0 letters at 6 months). These improvements were limited to the transplanted eye, with no parallel gains in the untreated eye, supporting a localized treatment effect.
Study leaders described the safety data as encouraging and emphasized that the degree of vision gain in the most severely affected patients was unexpected for this population. Because low‑dose outcomes were positive for safety and preliminary efficacy, the trial has progressed to higher dose cohorts, and the research team is actively monitoring the medium and high‑dose groups (150,000 and 250,000 cells) for safety and visual outcomes.
If ongoing monitoring continues to show acceptable safety, investigators plan to advance to subsequent trial phases to further define efficacy, optimal dosing, and long‑term durability. Researchers also expressed gratitude to trial participants for their contribution to evaluating whether RPESC‑RPE transplantation can become a viable future therapy for advanced dry AMD.
About this AMD and genetics research news
Author: Ananya Sen
Source: University of Michigan
Contact: Ananya Sen – University of Michigan
Image credit: Neuroscience News
Original research (open access): Safety and tolerability of RPESC‑RPE transplantation in patients with dry age‑related macular degeneration: Low‑dose clinical outcomes by Rajesh C. Rao et al., published in Cell Stem Cell. DOI cited in the original report.
Abstract (summary)
Safety and tolerability of RPESC‑RPE transplantation in patients with dry age‑related macular degeneration: Low‑dose clinical outcomes
Retinal pigment epithelium (RPE) atrophy in dry AMD undermines photoreceptor health and leads to progressive vision loss. Stem cell‑based RPE replacement seeks to halt or reverse this process and restore visual function. RPESC‑RPE‑4W is an adult RPE stem cell‑derived progenitor product that showed consistent safety and efficacy in preclinical testing. In the initial human trial cohort, six participants received 50,000 RPESC‑RPE‑4W cells delivered subretinally. No significant inflammation, tumor formation, or product‑related serious adverse events were reported. The subset of participants with poorer baseline vision demonstrated meaningful best‑corrected visual acuity gains at 12 months, supporting dose escalation to mid‑dose therapy for further study in dry AMD.