Gene therapy successful in treating rare retinal disorder

A successful treatment for an inherited cause of blindness could become the first gene therapy to receive approval from the U.S. Food and Drug Administration (FDA).

The gene therapy targeted one type of the retinal disorder Leber's congenital amaurosis (LCA) that was caused by mutations in the gene RPE65.

"This is great news for the revolution of gene therapy," says Jay Haynie, O.D., executive clinical director at Retina and Macula Specialists in Tacoma, Washington. "This will probably develop a platform to move into other areas of retinal disease. It doesn't change the standard management of a low-vision patient today, but what it does is change the outlook of retinal diseases that lead to blindness."

Spark Therapeutics announced the promising results of its randomized, controlled phase 3 trial in October and its intention to file for FDA approval in 2016. The trial involved 31 people with the RPE65 mutation. Twenty-one were provided gene therapy through Spark's product, SPK-RPE65, via injections in the eye during surgery, and 10 subjects served as a control group.

Over the course of one year, participants were tested on their ability to navigate a mobility course under a variety of light levels ranging from one lux (equivalent to a moonless summer night) to 400 lux (a brightly lit office) using the bilateral testing condition, according to Spark Therapeutics.

After a year, the gene therapy group improved by an average of two light levels, according to a report from The New York Times. Two-thirds of the group completed the course in the dimmest light, the Times reported. A secondary endpoint, visual acuity, was not met.

Spark Therapeutics released only partial data in October but said it would release more data at various scientific meetings in the coming months.

This particular treatment affects only a small group of patients: those with LCA caused by an RPE65 mutation. LCA is a rare disorder, estimated to occur in 2 to 3 of every 100,000 births, plus not all types are caused by this same mutation. However, Dr. Haynie says, SPK-RPE65 could be effective against other retinal disorders discovered to be caused by an RPE65 mutation. Beyond that, researchers could use the SPK-RPE65 therapy as a model for other retinal disorders caused by mutations in only one gene. However, it would be more challenging to develop an effective gene therapy for disorders with multiple mutations and other contributing factors, such as dry age-related macular degeneration and retinitis pigmentosa. And because gene therapy works by targeting a specific gene, it won't work for disorders for which the mutation is not yet known.

Dr. Haynie says it will be up to doctors of optometry to educate their patients about what this trial means, as low-vision patients may falsely believe a cure for their eye problems is right around the corner.

"It is great for those patients who have LCA, but it will leave lay people confused about what can be cured by gene therapy," he says. "We as providers are the ones who will find ourselves educating our patients ... but I would be extremely optimistic with patients. Gene testing for ocular disease has been going on for two to three decades without much excitement, and now we have some excitement."