Just a few weeks ago I noted the results from an early trial of a form of retinal patch, in which the patients involved showed striking signs of improved vision, considering their age and the degree to which their macular degeneration had advanced. Today another set of clinical trial results were published by a separate group using a similar approach - human embryonic stem cells are used to derive sufficient retinal pigment epithelium cells to create a structured patch, resembling retinal tissue in at least some aspects. The patch is then implanted into the retina, and sufficient cells survive and integrate to restore some function to areas damaged by the progression of age-related macular degeneration. That two teams are seeing positive outcomes from this type of approach is good news for the broader field.
The advance over prior efforts to produce a cell therapy for macular degeneration, present in both of these trials, lies in the methodologies that allow cells to form a more life-like retinal structure prior to implantation. Cells transplanted into the retina without that support largely die before they can do much good, and this is an issue across the entire spectrum of cell therapies. Many present cell therapies are only marginally beneficial precisely because the transplanted cells last a few days or a few weeks at most. They change the balance of local signaling for a while, and this can have quite useful effects, such as the suppression of inflammation achieved via mesenchymal stem cell therapies, but this doesn't realize the potential of cell therapies to achieve regeneration and replacement of tissue.
The tissue engineering community has, over the past few years, made meaningful progress towards the delivery of structured patches rather than cells on their own. For example, heart muscle patches have recently demonstrated much higher rates of cell survival and integration. Just like the retinal patches noted here, these are cells and scaffolds that are similar to the native tissue, more resilient and more effective. We should expect to see this type of approach spread widely throughout the field, now that it has been proven effective in multiple different tissues - though it will take some time, as each tissue type requires the establishment of its own recipes and methods.
The treatment, which consists of a layer of human embryonic stem cell-derived retinal pigment epithelium cells on an ultrathin supportive structure, was implanted in the retina of four patients. The patients were followed for up to one year to assess its safety. There were no severe adverse events related to the implant or the surgical procedure, indicating that the treatment was well-tolerated. There was also evidence that the implant integrated with the patients' retinal tissue, which is essential for the treatment to be able to improve visual function.
"This is the first human trial of this novel stem cell-based implant, which is designed to replace a single-cell layer that degenerates in patients with dry age-related macular degeneration. This implant has the potential to stop the progression of the disease or even improve patients' vision. Proving its safety in humans is the first step in accomplishing that goal." Dry age-related macular degeneration is the most common type of age-related macular degeneration. Over time, it can lead to loss of central vision, which can diminish people's ability to perform daily tasks like reading, writing, driving and seeing faces.
As part of the study, the research team also performed a preliminary assessment of the therapy's efficacy. One patient had improvement in visual acuity, which was measured by how many letters they could read on an eye chart, and two patients had gains in visual function, which was measured by how well they could use the area of the retina treated by the implant. None of the patients showed evidence of progression in vision loss.
Retinal pigment epithelium (RPE) dysfunction and loss are a hallmark of photoreceptors ultimately degenerate, leading to severe, progressive vision loss. Clinical and histological studies suggest that RPE replacement strategies may delay disease progression or restore vision. A prospective, interventional, U.S. Food and Drug Administration-cleared, phase 1/2a study is being conducted to assess the safety and efficacy of a composite subretinal implant in subjects with advanced NNAMD. The composite implant, termed the California Project to Cure Blindness-Retinal Pigment Epithelium 1 (CPCB-RPE1), consists of a polarized monolayer of human embryonic stem cell-derived RPE (hESC-RPE) on an ultrathin, synthetic parylene substrate designed to mimic Bruch's membrane.
We report an interim analysis of the phase 1 cohort consisting of five subjects. Four of five subjects enrolled in the study successfully received the composite implant. In all implanted subjects, optical coherence tomography imaging showed changes consistent with hESC-RPE and host photoreceptor integration. None of the implanted eyes showed progression of vision loss, one eye improved by 17 letters and two eyes demonstrated improved fixation. The concurrent structural and functional findings suggest that CPCB-RPE1 may improve visual function, at least in the short term, in some patients with severe vision loss from advanced NNAMD.