Stem Cell Trials for AMD and Stargardt Disease
Jan 24, 2012 - Very preliminary results are being reported today from two clinical trials of a treatment for Stargardt disease and age-related macular degeneration (AMD) using transplanted tissue derrived from human embryonic stem cells. This research paper in The Lancet shares early results from two patients: one with dry AMD, and one with a form of Stargardt disease.
Both patients are enrolled in small-scale safety studies (Phase 1 clinical trials) of a new cell-transplant therapy developed by Advanced Cell Technologies. These trials, which are being done at the Jules Stein Eye Institute at UCLA (University of California, Los Angeles), aim to enrol 12 patients with each condition. Both studies were launched about a year ago (see our previous stories about the AMD and Stargardt disease trials), and the investigators now have followed two patients for four months after treatment.
This is the first human trial of a transplant therapy derived from human embryonic stem cells to reach this stage, so it is important to note that these two patients experienced no complications after 16 weeks. Embryonic cells can become any type of cell, so although the transplanted cells have been modified to look and act like retinal pigmented epithelial (RPE) cells, such transplants might, in principle, be capable of causing a tumour or other abnormal growth. It is encouraging that no such problems have been observed so far.
The goal of this therapy is to revitalize the RPE, a layer of cells that makes up the foundation of the retina. These cells nurture and support the photoreceptors (the light sensitive cells in the retina) and are disrupted in people with both AMD and Stargardt disease. It is hoped that the transplanted cells would grow within the RPE restoring this foundation and improving vision.
In the patient with Stargardt disease, the research team confirmed that the transplanted cells established themselves within the RPE and were making new RPE cells that survived for at least 16 weeks. This was less clear for the individual with AMD, but that individual had not taken all of their immune-suppressing therapies in the first week after the transplant. Preventing the immune system from rejecting the transplant may be important for the success of this treatment.
Both patients appeared to have some improvements in their vision, increasing the number of letters they could read on an eye chart. These were particularly notable for the Stargardt disease patient. At the beginning of the study, the patient with Stargardt disease could only see hand movement, but by 12 weeks after the treatment, visual acuity had improved to 20/800 and the patient could read 5 letters on an eye chart.
“These findings are very hopeful,” says Dr. Bill Stell, FFB Director of Research Programs, “however these are very preliminary results, and we cannot say with certainty that this treatment is either safe or effective. These findings do encourage investigators to continue their efforts to establish whether this therapy is safe and effective for human use.”
“The study reported here is different from many of the stem-cell therapies we hear about these days,” says Dr. Stell, “because it does not aim to replace the photoreceptors. By replacing and rejuvenating the RPE, which is the foundation for retinal function, the investigators hope to revive some photoreceptors that are still living but have not been properly nourished or supported. This is similar to repairing the foundation of an old house. It does not give you a new house, but it may make an old house more functional.”
Many investigators are working towards replacement of lost photoreceptor cells with new ones derived from stem cells in the hope of restoring vision to people with advanced retinal degenerative disease. Some day such treatments might restore vision to someone who is completely blind. This approach is being pursued by several scientific groups funded by the FFB in Canada, such as those of Drs. van der Kooy, Wallace, Cayouette, and Bernier.
Embryonic stem cells are only one possible source of cells for transplantation into the retina. Other research groups are studying stem cells retrieved from the adult eye (Dr. Derek van der Kooy in Toronto) or induced pluripotent stem cells, which are derived from skin cells and other cell types and have been reprogrammed genetically to have stem cell-like potential. To learn more about stem cell therapies, see the FFB Stem Cell fact sheet.