1. Treatment with human-embryonic stem cell-derived (hESC-derived) retinal pigment epithelium led to improved visual acuity and vision-related quality-of-life measures for patients with age-related macular degeneration and Stargardt’s macular dystrophy.
2. No evidence of serious ocular or systemic safety issues, adverse proliferation, or rejection related to the hESC-derived tissue was observed, suggesting hESC-derived cells could provide a safe tissue source for medical disorders arising from tissue degeneration.
Evidence Rating Level: 2 (Good)
Study Rundown: HESCs are a potential therapeutic source of cells for diseases caused by tissue loss. Despite this potential, their capacity for self-regeneration raises safety concerns. Degeneration of the retinal pigment epithelium in age-related macular degeneration and Stargardt’s macular dystrophy is currently untreatable. This study investigated tolerability and safety of hESC-derived retinal pigment epithelium in patients with Stargardt’s macular dystrophy or age-related macular degeneration by surgically introducing hESC-derived retinal pigment epithelium in differing doses and measuring visual outcomes during follow-up.
Eight of 18 patients experienced improved visual acuity of at least 15 letters within the first year after surgery, corresponding to a clinically significant doubling of the visual angle. Participants also reported improvement in near and distant activities, general vision, and peripheral vision as measured with the National Eye Institute Visual Function Questionnaire 25 subscales. Additionally, hESC-derived cells were well tolerated for up to 37 months after transplant. Though this is the first report of safety and tolerability after transplantation of cells derived from pluripotent stem cells in individuals with any disease, results may be subject to placebo effect and examiner bias inherent in non-blinded study design.
This study was funded by Advanced Cell Technology.
In-Depth [prospective phase 1/2 clinical trial]: This study investigated the tolerability, safety, and efficacy of hESC-derived retinal pigment epithelium in patients with either age-related macular degeneration or Stargardt’s macular dystrophy. Nine patients with Stargardt’s macular dystrophy and nine patients with age-related macular degeneration were evenly divided into three dose-cohorts (dose group 1, 50,000 cells; dose group 2, 100,000 cells; and dose group 3, 150,000 cells). Patients were given immunosuppression therapy consisting of tacrolimus and mycophenolate mofetil for one week before the procedure and for 12 weeks after. Serial ophthalmic, physical, and laboratory examinations were done for a median follow-up of 22 months.
13 (72%) of 18 patients had an increase in subretinal pigmentation after surgery. In patients with age-related macular degeneration, at 12 months the median difference in change in visual acuity from baseline between treated and untreated eyes that did not have ocular surgery or develop cataracts was eight letters (range 4-23) for dose group 1, eight letters for dose group 2, and 15 letters for dose group 3. This result was significant (p=0.0117). The median difference in change in patients with Stargardt’s macular dystrophy was nine letters (range 9-9) for dose group 1, two letters (range 0-10) for dose group 2, and five letters for dose group 3. This difference was not significant due to limitation in sample size. No evidence of growth of transplanted tissue at the injection site suggestive of teratoma or ectopic tissue, adverse proliferation, or adverse safety issues related to the hESC-retinal pigment epithelium was demonstrated in any patient during the observation period. Four eyes developed visually significant progression of cataract requiring surgery, in one patient with age-related macular degeneration, and three with Stargardt’s macular dystrophy. Additionally, one patient developed acute postoperative endophthalmitis.
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