Researchers at the National Eye Institute (NEI) will launch a clinical trial to test 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), a leading cause of vision loss among people age 65 and older. There is no treatment for the geographic atrophy form of AMD.

A protocol which prevented blindness in preclinical research on animals, this will be the first clinical trial in the United States to use replacement tissues from patient-derived induced pluripotent stem cells (iPSC), reports Kapil Bharti, PhD, a senior investigator and head of the NEI Ocular and Stem Cell Translation Research Section. The NEI is part of the National Institutes of Health (NIH).

The Regenerative Therapy

This regenerative medicine-based therapy involves taking a patient’s blood cells and, in a lab, converting them into iPS cells, which have the potential to form 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, once RPE cells die, photoreceptors eventually also die, resulting in blindness. The therapy is an attempt to shore up the health of remaining photoreceptors by replacing dying RPE with iPSC-derived RPE.

More on the Production Process

Prior to being transplanted, the iPSC-derived RPE are 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 surgical tool designated specifically for that purpose.

The Study

A Phase I/IIa clinical trial protocol, the study will include patients with advanced-stage geographic atrophy and will receive iPSC-derived RPE implant in one of their eyes and be closely monitored for a period of at least one year to confirm safety.

Concerns: Oncogenic Potential

One major concern with such stem-based therapy is its oncogenic potential—the ability for cells to multiply uncontrollably and form tumors. In animal models, the researchers genetically analyzed the iPSC-derived RPE cells and found no mutations linked to potential tumor growth. Furthermore, the use of individual’s autologous (own) blood cells is expected to minimize the risk of the body rejecting the implant. The study will include more patients to assess the efficacy of the implant to prevent blindness and restore vision in patients with geographic atrophy should early stage safety be confirmed.

FDA Requirements for this Study

The FDA is requiring that as a condition to move forward with the study, a good manufacturing practice (GMP) set of protocols be established to ensure that the iPSC-derived RPE are clinical-grade product. GMP protocols are vital for evidencing the ability to reproduce and scale up production, should the therapy receive FDA approval.

Preclinical Leadership

The NEI Intramural Research Program supported preclinical research for the trial via a NIH Common Fund Therapeutic Challenge Award. The clinical trial will be conducted at the NIH Clinical Center in Bethesda, MD.

Source: National Institutes of Health

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