NIH’s stem cell-based AMD therapy set for first human trial

NIH’s National Eye Institute has developed an iPSC-based therapy to prevent blindness in dry age-related macular degeneration. (Pixabay)

Induced pluripotent stem cells (iPSCs)—adult cells that are reprogrammed back to an embryonic state—hold promise as regenerative medicines. Researchers at the NIH’s National Eye Institute (NEI) have developed such a therapy to prevent blindness in dry age-related macular degeneration, and they have turned up positive animal data that set the stage for a human trial.

AMD is characterized by the loss of the retinal pigment epithelium (RPE), a thin cell layer that nurtures photoreceptors—the light-sensing cells in the retina. The NEI’s iPSC-derived therapy is designed to replace dying RPE cells and therefore salvage the eye before vision loss occurs.

The NEI scientists took blood cells from AMD patients, converted them into iPSCs and directed them to become RPE tissue, the team reported in the journal Science Translational Medicine. The iPSC-derived RPE cells were grown in a single layer—just like how they exist naturally—on a biodegradable scaffold designed to promote integration once they reach the retina.

That protocol “helps ensure that the transplanted cells function reliably and that unintended consequences are minimized,” said Kapil Bharti, Ph.D., head of the NEI Unit on Ocular and Stem Cell Translational Research and the lead investigator for the animal study, in a statement. “[It] also minimizes the chance of rejection by developing the iPSC-RPE with an individual’s autologous blood cells.”

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One major concern that limits iPSC’s therapeutic use in humans is that it can propagate uncontrollably and develop into cancer. The NEI researchers designed their manufacturing process to avoid cancer-causing mutations.

In studies in rat and pig models, the scientists reported that their lab-made cells had integrated within the animal retina 10 weeks after the RPE patches were implanted and safely reversed degeneration of the animals' retinas.

Immunostaining confirmed that the RPE expressed the gene RPE65, suggesting the cell layer had reached a level of maturity necessary for regenerating visual pigment within the photoreceptors. Further tests showed that the implanted RPE cells exhibited "phagocytosis," a crucial function that involves trimming the photoreceptors' outer segments to maintain a healthy size, according to the statement.

Moreover, electrical pulses recorded from the photoreceptors after the RPE transplant were normal. A set of control animals treated with an empty scaffold, by contrast, experienced photoreceptor death.

Using stem cells to grow healthy tissue is a popular idea for treating eye diseases. Scientists led by the University of Southern California’s Roski Eye Institute built an embryonic stem cell-derived retinal implant that also aims to replenish RPE in dry AMD, and they’ve reported early results on four dry AMD patients, showing a positive trend toward sight improvement. Another team at Mount Sinai developed a potentially safe way to activate stem cell-like Müller glial cells in mammals so they divide into new photoreceptors.

With the positive preclinical data and robust GMP protocols to make the therapy, the NEI team has started planning of a phase 1 clinical trial testing its iPSC-based therapy in people.

“If the clinical trial moves forward, it would be the first ever to test a stem cell-based therapy derived from induced pluripotent stem cells for treating a disease,” Bharti said.