Potential New Treatment Approach for Age-related Macular Degeneration

A patch that uses patients’ own stem cells to protect them from vision loss will soon begin phase 1 trials.

Results of proof-of-concept studies of a stem-cell patch designed to protect age-related macular degeneration (AMD) patients from vision loss were reported by the National Eye Institute’s Kapil Bharti, PhD, at the Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting in Seattle, WA, on May 4, 2016. An abstract on the patch was also published in the ARVO proceedings.

Advanced AMD, one of the leading causes of blindness in elderly patients, is initiated by the atrophy of a monolayer of cells in the back of the eye. These cells are known as retinal pigment epithelial (RPE) cells. Researchers have reasoned that replacing RPE cells in AMD patients could protect the light-activated signal-transmitting photoreceptor neurons that overlie them from dying and thereby preserve vision. This reasoning is driving the development of a number of stem-cell-based approaches to RPE replacement that include the NEI patch.

The patch, which has been tested in pigs, contains RPE cells that have differentiated from the induced pluripotent stem cells (iPS) of three AMD patients. To form the patch, these autologous RPE cells are attached to a scaffold made of a biocompatible, biodegradable polymer, poly (lactic co-glycolic) acid (PLGA). About 70,000 to 80,000 cells are needed for a 4 x 2 mm patch, and the scaffold the cells are attached to lasts about 10-12 weeks after implantation.

To produce the RPE cells needed for the patch, the NEI team has developed a highly reproducible, efficient process that yields pure cells. The iPS cells are differentiated into committed RPE cells by using a developmentally guided protocol, which the NEI team has found to produce better results than other protocols. This process, which takes 157 days, has been streamlined by using in-process quality controls and mapping every step.

After the cells have been transferred to the scaffold, the patch’s function is confirmed by electrophysiological measurements and assessment of its polarized cytokine secretion as well as its ability to phagocytose photoreceptor outer segments, which degrade, build up in the eye over time, and hamper eye function.

To test how the patch works in vivo, the NEI team has inserted it into the retinas of pigs with laser-induced RPE injury that has caused RPE atrophy and photoreceptor cell degeneration. Using optical coherence tomography and multi-focal electroretinography, the team has confirmed that the patch can rescue photoreceptor cells from degeneration in this animal model of AMD. These results provide the data needed to initiate IND-enabling studies for a phase 1 clinical trial of the patch in AMD patients. However, at this point, it is unclear how long the transplanted RPE cells will survive.