Teams of researchers in the United States and Britain reported this week that preliminary results from two gene therapy clinical trials for Leber's congenital amaurosis - the first ever - suggest treatment is safe in the short term and can restore some vision.
The surgery delivers a healthy copy of the human retinal pigment epithelium-specific 65 kDa protein gene (RPE65) into the retina using a harmless virus or "vector" to carry the gene into the cells. Each patient received a single subretinal injection of RPE65 during vitrectomy.
All three participants in the U.S. study showed evidence of improvement in retinal function as evidenced by pupillary light reflex. In addition, all three reported having improved vision in dimly lit environments beginning two weeks after surgery. Two of the volunteers who could only see hand motions were able to read a few lines of an eye chart.
Five-month data from the U.S. study showed that the postoperative average visual-acuity logMAR score improved by 0.28 for Patient 1, whose scores increased from hand-motion recognition (0 letters) to a Snellen equivalent of 20/1050 (approximately 3 lines on the eye chart) (P<0.001 by the Wilcoxon rank-sum test). The logMAR score for Patient 2 improved by 0.45, from hand-motion recognition (0 letters) to a Snellen equivalent of 20/710 (22.5 letters, or >4.5 lines on the chart) (P<0.001 by the Wilcoxon rank-sum test). Patient 2 also showed an increase in visual acuity in his left (untreated) eye, with an increase in the Snellen equivalent from 20/500 to 20/220 and an improvement in the logMAR score of 0.36. For the right (treated) eye of Patient 3, the change in the logMAR score was 0.34, more than 3.5 lines of letters (P=0.002 by the Wilcoxon rank-sum test).
British researchers, reporting 12 months of data, observed no clinically significant change in visual acuity or in peripheral visual fields on Goldmann perimetry in any of the three patients enrolled in their study.
But one participant in the British study did experience improved visual function. This 18-year-old patient had better baseline visual acuity in both the study eye and control eye than the two other participants, and had less advanced retinal disease at baseline. According to newspaper accounts this participant couldn't walk through a darkened room unassisted before surgery. Now he can walk home at night, unassisted. The 18-year old said this small improvement in his vision has made a big difference in his life.
Both studies reached the primary outcome of safety. Of all six patients, only one patient developed a macular hole, but researchers believe it was unrelated to the treatment, since they observed no signs of inflammation or acute retinal toxicity. They hypothesize that the macular hole was caused by contraction of a preexisting membrane stimulated by the surgical procedure, or it may have been caused by the surgical procedure itself.
Researchers say that the ability to deliver genes by subretinal injection to an extremely fragile site in the eye without complication has been encouraging.
In an editorial appearing along with the study results, Joan Miller, MD, of the Massachusetts Eye and Ear Infirmary called the results "suggestive of efficacy."
She wrote: "The preliminary results from these investigations suggest that in the short term, the procedure is safe. Moreover, the data are suggestive of efficacy. Both groups recognize that longer follow-up and additional subjects are necessary to provide satisfying safety data. Certainly, efficacy data will be available only in larger trials."
The April 27 issue of the New England Journal of Medicine includes videos from both the U.S. and British studies.