Phase 1 Safety Assessment of CPCB-RPE1, hESC-derived RPE Cell Coated Parylene Membrane Implants, in Patients with Advanced Dry Age Related Macular Degeneration

It is estimated that by 2020, over 450,000 Californians will suffer from vision loss or blindness due to the age-related macular degeneration (AMD), the most common cause of retinal degeneration in the elderly. AMD is a progressive ocular disease of the part of the retina, called the macula, which enables people to read, visualize faces, and drive. The disease initially causes distortion in central vision, and eventually leads to legal blindness. A layer of cells at the back of the eye called the retinal pigment epithelium (RPE), provides support, protection, and nutrition to the light sensitive cells of the retina; the photoreceptors. The dysfunction and/or loss of these RPE cells is believed to play a critical role in the subsequent death of photoreceptors and resulting loss of vision in AMD. Hence, if RPE cells can be restored, it may be possible to prevent or delay progressive vision loss in patients with AMD. We are developing a therapy to replace RPE cells in patients with a form of AMD known as geographic atrophy. The RPE cells are delivered on a synthetic membrane, just as normal RPE cells in the eye are arranged as a thin layer of cells on a substrate known as the Bruch’s membrane. We have also shown that our approach of delivering the RPE as a sheet into diseased animal eyes has a much better chance of restoring retinal function than if these cells were injected as a suspension. In this current grant from CIRM, we are seeking to translate this preclinical work and to test this product in a Phase I clinical trial in patients with geographic atrophy.

It is estimated that by 2020, over 450,000 Californians and 3 million in the US will suffer from vision loss or blindness due to age-related macular degeneration (AMD), the most common cause of retinal degeneration in the elderly. AMD is a disease that affects the central part of the retina, called the macula, which enables people to read, visualize faces, and drive. The disease initially causes distortion in central vision, and eventually leads to legal blindness. Loss of vision is due to dysfunction and death of the retinal pigmented epithelium (RPE), a layer of cells at the back of the eye that provides support for the light-sensitive photoreceptors. Currently there are no available treatment options for most patients. Our approach is to replace the dying RPE with a patch of new RPE derived from stem cells. Our effort, called the California Project to Cure Blindness, involves a team of world-class experts from the University of Southern California Roski Eye Institute (Mark Humayun, MD PhD and David Hinton, MD), the University of California-Santa Barbara, the California Institute of Technology, the City of Hope, and Regenerative Patch Technologies LLC. Our goal is to develop a therapy for patients with the dry form of AMD known as geographic atrophy. A thin layer of stem cell-derived RPE cells is grown on a synthetic scaffold and delivered to the back of the eye via a surgical procedure. The implant is delivered underneath the retina using a custom delivery tool. Previous studies in animals have shown that the RPE implant can promote survival and function of the photoreceptors, and our application to begin a clinical trial was cleared by the FDA. In this ongoing phase I/IIa clinical trial we are assessing safety of the implant. The study will include two cohorts, each of 10 patients. For the first cohort, the study population will be patients with advanced, dry AMD with evidence of significant geographic atrophy. As the safety and tolerability of the implant is demonstrated in the first cohort, patients with less advanced disease will be recruited into a second cohort. We will also assess the vision of patients to see if there are any changes in their ability to see.