December 2009




One year and counting: gene therapy for Leber’s congenital amaurosis

by Maxine Lipner Senior EyeWorld Contributing Editor


Intact genes continue to restore vision

Patients with Leber’s congenital amaurosis (LCA) continue to enjoy improved vision one year after receiving gene therapy for the inherited form of blindness. Results published in the August 2009 issue of the New England Journal of Medicine indicate that the three young adults who received gene therapy for the RPE 65 gene mutation continued to show improved vision in dim light.

“Leber’s congenital amaurosis is a genetic condition that has to do with misspellings in the genes that we inherit from our parents,” said Brian P. Brooks, M.D., Ph.D., tenure track investigator, National Eye Institute, Bethesda, Md. “The genetic types all have in common the fact that they’re important in the function of the photoreceptors.” These may be more important for rods, cones, or both, depending on the specific gene that’s involved.

There were three legally blind patients, ages 22, 24, and 25, included in the phase study, conducted by Artur V. Cideciyan, Ph.D., research associate professor of ophthalmology, University of Pennsylvania School of Medicine, Philadelphia, and his team of investigators. “In this particular case the authors are looking at a form of Leber’s congenital amaurosis caused by mutations in RPE 65,” Dr. Brooks said. “It’s a gene that is normally expressed in the retinal pigment epithelium and is important in recycling the chemical form of vitamin A that is used in the visual cycle to enable us to see.”

Investigators injected healthy copies of the RPE 65 gene to correct this genetic defect. Each patient received one injection into retinal regions that were determined to be impaired yet intact. “The procedure is done by using a virus to deliver a normal copy of the gene with a subretinal injection,” Dr. Brooks said. “The cells take up the normal gene and we think start expressing it because we now see an effect on vision in those areas that were treated.” At the one-year mark, results indicated that the new genes continued to make the needed protein, increasing all three patients’ sensitivity to light.

One-year results

Results were promising. “The study showed that by the measures researchers had in these three patients, it appeared that it continues to be safe, the patients did not have any adverse reactions, and they were able to see a couple of months after treatment persisted for one year,” Dr. Brooks said. “When they tested the patients’ ability to see a dim light, the patients were able to see a much dimmer light than they could prior to treatment.”

In one case, one year after treatment a patient appeared to gain further functionality. “One patient appeared over the course of time to be able to better use the sensitivity of the retina that she had previously gained,” Dr. Brooks said. “Anecdotally she was able to see a digital clock in her parents’ car that she couldn’t previously see.”

Investigators theorize that she in some way learned to use this patch of retina that had gained new sensitivity right after the treatment.

New possibilities

This opens the door for others to enjoy such improvement. “One of the unanswered questions is, now that we’re aware of this in at least one patient, can we perhaps train patients to become more aware of these areas and better utilize the vision that they’re given?” Dr. Brooks said.

Dr. Brooks is encouraged by the results. “It is fantastic that the effect of the gene has been this long-lived,” he said. “It’s encouraging that we’re dealing with a treatment where it doesn’t look like we’re going to have to do repeat injections every few months.”

While it is too early to give a precise timeline on when the treatment might become available to all who need it, Dr. Brooks sees the research as continuing to progress. “We are trying to move this therapy into younger patients to see if we can get an even better effect,” he said. “It’s hard to say at this stage of the game when this will be available in the doctor’s office.”

Going forward, Dr. Brooks envisions this treatment as likely helping a wider range of patients. “In cases where there is a clear pattern of inheritance where we think the problem is that a patient is simply missing the function of a given gene, I think that this methodology will have much broader implications,” he said. “I think it’s only a matter of time, given the success that we’ve seen with RPE 65-related treatment, before other forms of LCA are attempted and other inherited blinding diseases of the retina can be treated.”

Editors’ note: Dr. Brooks has no financial interests related to his comments.

Contact information

Brooks: 301-451-2238,

One year and counting: gene therapy for Leber’s congenital amaurosis One year and counting: gene therapy for Leber’s congenital amaurosis
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