Leber congenital amaurosis (LCA) is an inherited disorder leading to vision loss beginning in childhood. Researchers have found that gene therapy can improve eyesight and retinal sensitivity in in LCA patients, with positive results peaking at one to three years after treatment before diminishing.
In a clinical trial supported by the National Institutes of Health's National Eye Institute, a subset of participants underwent extensive tests routinely to assess their vision and capture images of their retina from baseline until six years after receiving treatment. According to these tests, areas of the retina that have been treated quickly developed visual sensitivity and expanded before contracting.
Samuel Jacobson, M.D., Ph.D., led the clinical trial which was held at the Scheie Eye Institute, Philadelphia at the University of Pennsylvania. He said that the clinical trial has shown that gene therapy can be used for alleviating LCA, pointing out the possibility of treating previously incurable and untreatable conditions involving the retina. And while the current gene therapy that the researchers are using does not correspond to a permanent treatment, the knowledge gained in the clinical trial opens up the opportunity to improve the therapy so that vision may be restored in LCA patients for longer periods of time.
Around 10 percent of people suffering from LCA have a mutated form of the RPE65 gene, which is responsible for producing a key protein in retinal pigment epithelium cells. Photoreceptors in the eye rely on these cells to maintain light sensitivity. When the cells die due to a disruption in their protein supply, it affects the function of photoreceptors. When retinal pigment epithelium cells are no longer around, photoreceptors stop functioning, ceasing eye-to-brain communication.
The clinical trial started in 2007 with 15 subjects, each one given shots of a harmless virus carrying RPE65 genes to their retinas. Within days of getting the injections, some patients had reported increased ability to see lights, though dim, that they have never seen before.
"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," said Jacobson.
Current results hint at a number of possible strategies for improvement, like staging the disease before gene therapy begins to clarify potential benefits for every individual or integrating gene therapy with medication for protecting cell loss in the retina or boosting the visual cycle. It's also possible that a second round of treatment may yield better results for LCA patients.
