A new National Eye Institute (NEI) clinical trial is testing the safety of a novel patient-specific stem cell-based therapy to treat geographic atrophy, the advanced “dry” form of age-related macular degeneration (AMD), which currently has no treatment.

“The protocol, which prevented blindness in animal models, is the first clinical trial in the U.S. to use replacement tissues from patient-derived induced pluripotent stem cells (iPSC),” said Kapil Bharti, Ph.D., a senior investigator and head of the NEI Ocular and Stem Cell Translational Research Section.

In animal models, the researchers genetically analyzed the iPSC-derived RPE cells and found no mutations linked to potential tumor growth

The therapy uses the patient’s blood cells and converts them into iPS cells, which may take the form of almost any type of cell in the body. The iPS cells are programmed to become retinal pigment epithelial (RPE) cells, the type of cell that dies early in the geographic atrophy stage of macular degeneration.

RPE cells nurture photoreceptors, the light-sensing cells in the retina. In geographic atrophy, RPE cells die and lead to the demise of photoreceptors, which results in blindness. The therapy is an attempt to shore up the health of remaining photoreceptors by replacing dying RPE with iPSC-derived RPE.

The making of RPE cells

Before transplantation, the iPSC-derived RPE is grown in sheets one cell thick, replicating their natural structure within the eye. This monolayer of iPSC-derived RPE is grown on a biodegradable scaffold designed to promote the integration of the cells within the retina. Surgeons position the patch between the RPE and the photoreceptors using a specially designed surgical tool.

Under the phase I/IIa clinical trial protocol, 12 patients with advanced-stage geographic atrophy will receive the iPSC-derived RPE implant in one of their eyes and be closely monitored for at least one year to confirm safety. In animal models, the researchers genetically analyzed the iPSC-derived RPE cells and found no mutations linked to potential tumor growth.
The use of an individual’s autologous (own) blood cells is expected to minimize the risk of the body rejecting the implant.

Should early safety be confirmed, later study phases will include more patients to assess the efficacy of the implant to prevent blindness and restore vision in patients with geographic atrophy.