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EW RETINA 66 June 2015 by Maxine Lipner EyeWorld Senior Contributing Writer anatomic outcomes may be at the cellular level and below current imaging resolution thresholds." Moving forward "The collaborators, who include professors at Bascom Palmer, Harvard, Wills Eye, and Moorfields Eye Hospital, have agreed to move forward into the next phase of the project," Dr. Schwartz said, adding that this would take the research into phase 2A and B studies. Overall, investigators are enthu- siastic about the potential that the approach might have. "As a group, we're excited and enthusiastic about moving forward," Dr. Schwartz said. "We hope that down the line there is a real chance we could be talking about regenera- tive ophthalmology." EW Reference Schwartz SD, Regillo CD, Lam BL, et al. Human embryonic stem cell-derived retinal pigment epithelium in patients with age-re- lated macular degeneration and Stargardt's macular dystrophy: follow-up of two open- label phase 1/2 studies. Lancet. 2015 Feb 7;385(9967):509–16. Editors' note: Dr. Schwartz has no financial interests related to this article. This work was the first success- ful stem cell-derived tissue trans- plantation in humans ever pub- lished, he noted, adding that this makes it important from a regener- ative medicine standpoint. From an ophthalmic standpoint, Dr. Schwartz noted there are other treatments in the pipeline for dry AMD that are further along. Still, he views the use of such tissue transplantation as an exciting and promising area. In the study, vision was considered as part of the safety profile. Investigators found that there was no visual loss, Dr. Schwartz reported. "In fact, almost half of the patients gained vision," he said. "This is outside of our clin- ical experience with these diseases." However, at this point investigators do not have an explanation for why patients gained vision, he stressed. There are many explanations for the gain in vision, including placebo effect and chance. "In early safety studies, it's hard to hang your hat on function- al results with small numbers of patients," Dr. Schwartz said. "We observed some anatomic results that are promising, but they don't clearly explain the functional improvements observed in some of the participants. Detailed work is ongoing in this area as the "Even though the cause of their loss is different in the 2 conditions, the final common pathway as vision is lost, especially at the end stages, is loss of retinal pigment epithelium," Dr. Schwartz said. The consequence of this loss of retinal pigment epi- thelium includes central blindness. As part of the dose-ranging, placebo-controlled study, investiga- tors transplanted stem cell-derived retinal pigment epithelium into the subretinal space, he continued. The 18 patients included in the study were then followed for a mean of 22 months. "We immunosuppressed patients 1 week prior to transplan- tation and for up to 6 months following transplantation, as mild to severe rejection was a legitimate concern," Dr. Schwartz said. "We carefully surveilled patients for safety issues including immune rejection, tumor formation, unwant- ed tissue differentiation and visual loss." Investigators also considered vision from a safety perspective. While the immune suppression was a little hard on the elderly patients, investigators were pleased to find that the study demonstrated a good safety profile. No safety signals related to the transplanted stem cell progeny or the surgeries, according to Dr. Schwartz. Honing in on safety- related issues S targardt disease and atrophic or dry age-relat- ed macular degeneration (AMD) are very different conditions that can have the same result. "Macular degeneration is the leading cause of new blindness in the developed world," said Steven D. Schwartz, MD, Ahmanson pro- fessor of ophthalmology, retina divi- sion chief, Jules Stein Eye Institute, David Geffen School of Medicine, UCLA, adding that approximately 80% of that is due to dry macular degeneration, which by definition affects older individuals. Stargardt disease robs people of their central vision during the prime of their life at an incidence ranging from 1 in 10,000 to 1 in 15,000, he said. Both are currently untreatable, unmet medical needs. However, in a recent study, a common approach was tried—use of stem cell therapy. In the study, published in the February 2015 issue of Lancet, investigators considered the safety of treating patients with human stem cell-derived retinal pigment epithelium. "Stem cells, or the idea of regenerative medicine, has held tremendous promise for a number of conditions across the spectrum of all human disease," Dr. Schwartz said. "Together with my collaborators, I felt that the time had come to move from the laboratory to the bedside and test the safety of these complex biological entities and see what we could discover about them." First successful transplant For the investigation, the stem cell line was derived from just one cell that a family had allowed to be taken from an in vitro-fertilized embryo, Dr. Schwartz explained. The collaborators were able to grow that one cell into a whole line of stem cells, cells that could differentiate into any cell type in the body. What investigators did was induce these cells to differentiate into retinal pigment epithelium, which is com- promised and then absent in both dry AMD and Stargardt disease, he explained. Transplanting stem cell-derived retinal pigment epithelium New research on stem cell treatment holds tremendous promise for some ophthalmic conditions. Source: National Eye Institute

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