The Gift of Sight: Treating Blindness with Gene Therapy

By Johnathan Nieves

Findings from a new study show that gene therapy may be effective in treating a rare disease that progresses to total blindness by adulthood.

Imagine how difficult daily activities would be without being able to see. For 1.3 million Americans today, that is the reality they face.  For a subset of individuals, though, gene therapy may be the answer to curing their debilitating disease. Findings from a study published March 3^rd in Science Translational Medicine showed that gene therapy may be effective in treating Leber’s congenital amaurosis (LCA), a rare genetic disease that progresses to total blindness by adulthood.

Gene therapy for LCA, which produced dramatic improvements last year in 12 children and young adults who received the treatment in a clinical trial, has cleared another hurdle.  In the human trial for LCA reported last year, researchers at PENN Medicine and The Children’s Hospital of Philadelphia treated only one eye in each of their 12 patients. Because the treatment was experimental, researchers left one eye untreated in the event of unexpected complications. After the patients experienced partially restored eyesight in their treated eyes, many were eager to receive the same treatment in the other eye.

The same research team that conducted the human trial now reports that a study in animals has shown that a second injection of genes into the opposite, previously untreated eye is safe and effective. The study suggests that patients with LCA who benefited from gene therapy in one eye may experience similar benefits from treatment in the other eye.

“We designed this study to investigate the immunological consequences of administering the

gene therapy injection to the second eye after treating the first one,” said corresponding author Jean Bennett, M.D., Ph.D., F.M. Kirby professor of Ophthalmology at the University of Pennsylvania School of Medicine. “The good news is that in animals, the second injection, like the first, is benign.”

 As in the human trials of this gene therapy, the researchers packaged a normal version of the missing gene that causes LCA into a vector. The vector, a viral messenger that is used to incorporate a gene into a cell’s DNA, was used to deliver the gene therapy to cells of the retina, the light sensing region of the eye. Once in the retina cells, the vector is able to incorporate the gene into the cell’s DNA. Once incorporated into the DNA, the cell’s DNA reading machinery can translate the gene and produce an enzyme that restores retinal function, effectively reversing blindness (to view an animation of this processess click on the image above).

 Although the virus used in the study does not cause human disease, it previously set off an immune response that cut short the initial benefits of gene therapy. In the current study, the team found no evidence of toxic side effects in the 10 animals that received treatment. All the animals, which had been specially bred to have inherited blindness, had improved vision, and showed no toxic effects from the treatment.

The study “provides encouraging indications that immune responses will not interfere with human gene therapy in both eyes,” said co-author Katherine A. High, M.D.  Additionally, the results may set the stage for gene therapy in LCA patients who were excluded from the previous trial. At present, the research team is planning another clinical trial of LCA gene therapy, which may include some of the patients from the first human trial.

 To view the original press release pertaining to this article, click here.