Subretinal transplantation of retinal pigment epithelium derived from human embryonic stem cells (hESCs) appears to be a well-tolerated means of treating age-related macular degeneration and Stargardt’s macular dystrophy, suggest two open-label phase I/II studies.
Due to their immunoprivileged nature, hESCs have great therapeutic potential particularly for diseases affecting the eye, say Steven Schwartz (Jules Stein Eye Institute, Los Angeles, California, USA) and colleagues. But they add that “their plasticity and unlimited capacity for self-renewal raises concerns about serious safety issues”.
The researchers assessed the safety and tolerability of subretinal transplantation of hESC-derived retinal pigment epithelium in nine patients with Stargardt’s macular dystrophy and nine with atrophic age-related macular degeneration. The median age of the patients was 50 years and 77 years, respectively.
Three doses of cells – 50,000, 100,000 and 150,000 – were injected into the eye with the worst vision for each disorder and the patients took an immunosuppressant for a week before surgery and for 12 weeks afterwards.
Over a median follow-up of 22 months, no systemic safety issues were identified and concerns regarding teratoma formation, immune reactions and differentiation of cells into unwanted ectopic cell types were not realised.
The only adverse events were those characteristic of pars plana vitrectomy surgery, note the researchers, including preretinal patches of non-contractile, transplanted retinal pigment epithelium in three eyes and endophthalmitis in one patient.
An increase in subretinal pigmentation, symbolic of successful transplantation, was seen in 13 of the 18 patients. And visual acuity, although tested as a safety measure for monitoring vision loss, improved following surgery in 10 eyes, remained the same or improved in seven eyes, and decreased by more than 10 letters in one eye. The untreated fellow eyes did not show similar improvements.
Improvements following transplantation were seen for general and peripheral vision as well as near and distance activities, increasing by 16 to 25 points in the 3 to 12 months following surgery in patients with atrophic age-related macular degeneration and by 8 to 20 points in those with Stargardt’s macular dystrophy.
For eight patients, visual acuity improved by at least 15 letters during the first year after transplantation, corresponding to a clinically significant “doubling of the visual angle”, the team writes in The Lancet.
In a related commentary, Anthony Atala (Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA), says the study is “a major accomplishment”.
“Much work remains to be done before hESC and induced pluripotent stem cell therapies go beyond regulatory trials, but the path is now set in motion”, he concludes.
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