Summary: A new clinical trial suggests stem cell therapy may restore vision in people with advanced dry age-related macular degeneration, a disease that currently has no cure. Researchers transplanted retinal pigment epithelial stem cells, derived from adult postmortem eye tissue, into patients’ eyes.
The treatment was safe and led to surprising vision improvements, with some patients gaining the ability to read 21 more letters on an eye chart after one year. These results mark an early but promising step toward regenerative therapies for a leading cause of blindness.
Key Facts
Stem Cell Source: Retinal pigment epithelial cells derived from adult eye-bank tissue.Safety Confirmed: No serious inflammation or tumor formation after transplantation.Vision Gains: Patients improved by 21 letters on an eye chart in one year.
Source: University of Michigan
In the United States, age-related macular degeneration is a leading cause of irreversible vision loss in people who are 60 and older.
It affects the central portion of the retina, called the macula. This region is packed with cells responsible for high-resolution color vision.
When tested with an eye chart, the participants in the low-dose group were able to see 21 more letters after a year. Credit: Neuroscience News
About 20 million U.S. adults are living with some form of AMD. Although they cannot see objects that are directly in front of them, their peripheral vision is unaffected.
Current treatments slow the disease, but none restore vision.
In a study, published in Cell Stem Cell, researchers used retinal pigment epithelial stem cells derived from adult postmortem eye tissue in a phase 1/2a clinical trial. These early phase trials are used to determine whether a therapy intervention is safe.
There are two types of macular degeneration: dry and wet.
More than 90% of people with this condition have the dry form, which is caused by dysfunction and eventual loss of retinal pigment epithelial cells.
In early stages of AMD, these cells do not function properly. In late stages, they die and do not regenerate.
As the disease progresses, several areas inside the central eye lose these cells.
In the current study, patients with advanced dry AMD received transplanted stem cells, originally isolated from eye-bank tissues. These adult stem cells were specialized and could only develop into retinal pigment epithelial cells.
Six patients received the lowest dose of transplanted stem cells (50,000 cells) through a surgical eye procedure.
In all of them, the treatment was safe and did not cause serious inflammation or tumor formation.
The participants also experienced improved vision in the transplanted eye; the non-transplanted eye did not have these improvements, hinting that the approach could provide a new therapeutic avenue.
“Although we were pleased with the safety data, the exciting part was that their vision was also improving,” said Rajesh C. Rao, M.D., Leonard G. Miller Professor of Ophthalmology & Visual Sciences, and an associate professor of pathology and human genetics.
“We were surprised by the magnitude of vision gain in the most severely affected patients who received the adult stem cell-derived RPE transplants. This level of vision gain has not been seen in this group of patients with advanced dry AMD.”
When tested with an eye chart, the participants in the low-dose group were able to see 21 more letters after a year.
The team is now following the 12 other patients who received medium and high doses of 150,000 and 250,000 cells.
If no safety concerns arise, the research team will proceed with the next phases of the clinical trial.
“We are grateful to all our participants who are allowing to better understand whether this intervention is safe enough to be a future therapy,” Rao said.
“These kinds of NIH-funded studies can help us offer advanced treatments in the field of regenerative medicine, and we are happy we can offer this first-in-human, cutting-edge clinical trial at the University of Michigan.”
About this AMD and genetics research news
Author: Ananya Sen
Source: University of Michigan
Contact: Ananya Sen – University of Michigan
Image: The image is credited to 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. Cell Stem Cell
Abstract
Safety and tolerability of RPESC-RPE transplantation in patients with dry age-related macular degeneration: Low-dose clinical outcomes
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.