Gene therapy for blindness dims a bit

After initial improvement seen in three patients with rare inherited disease, vision cells die

illustration of gene therapy in retina

NO GAIN  Patients with an inherited form of blindness experienced temporary gains in vision after receiving gene therapy. But the retina of one person shows that nearly six years after the treatment, vision cells died in the treated area (outlined upper left corner; cooler colors signify cell death) and in the rest of the retina. 

S.G. Jacobson et al/NEJM 2015

Gene therapy for a rare form of inherited blindness improves sight temporarily but can’t yet save vision cells from dying.

Light-gathering rod and cone cells continued to die in the retinas of three people despite gene therapy to correct Leber congenital amaurosis, researchers report online May 3 in the New England Journal of Medicine. A mutation in a gene called RPE65 caused the people’s blindness. That mutation impairs recycling of light-gathering proteins in the eye, leading to the death of rods and cones, also called photoreceptors.

Beginning in 2007, Samuel Jacobson of the University of Pennsylvania School of Medicine and colleagues injected viruses carrying a healthy version of the gene under the retina of one eye in each of 15 people with the disease. The team reports results from three of the participants, who were followed up to nearly six years after getting the treatment.

All three had initial improvement in how the retina responds to light in the first year after treatment, and one continued to improve for another two years. But after those short-term gains, the patients’ retinas began to lose light sensitivity again. Researchers measured this sensitivity by shining light of various intensities on the people’s retinas and recording the dimmest light they could see. “The dimmer the light they can detect, the more sensitive they are,” study coauthor Artur Cideciyan, also from the University of Pennsylvania, said in an email. In two of the patients, the retina had fewer photoreceptors at the end of the study than before getting the therapy, indicating that cells were still dying, the researchers report.

There is no reason for alarm that gene therapy won’t work to treat blindness, says Jean Bennett, a molecular biologist also at the University of Pennsylvania. She has conducted similar gene therapy trials but was not involved in this study. “There was a high amount of data selection here,” she says. Findings from those three people may not be typical for the rest of the study participants.

Jacobson’s team did not compare disease progression in the treated eye with the untreated eye. “I think the jury is still out as to whether the changes they see are due to normal aging” or the disease, Bennett says.

Even with diminished sensitivity, patients may still benefit from the therapy, she says. “This is just a number scientists can measure,” Bennett says. “It doesn’t really reflect how this affects someone’s life.”

Jacobson declined an interview with Science News, saying that the data stand for themselves. In a press release, he said that although the gene therapy was not the permanent fix the researchers had hoped for, the results may help improve future treatment. “We’ve been able to positively alter and extend the visual life of patients with LCA, and we now have to develop workable strategies for extending it even further,” he said.  

Tina Hesman Saey is the senior staff writer and reports on molecular biology. She has a Ph.D. in molecular genetics from Washington University in St. Louis and a master’s degree in science journalism from Boston University.

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