Experimental gene therapy for blindness considered by FDA

Christian Guardino is one patient who benefited from an experimental gene therapy treatment to improve vision loss. Earlier this year he auditioned for the show "America's Got Talent."

Story highlights

  • Leber's congenital amaurosis causes severe visual impairment beginning in infancy
  • Luxturna gene therapy supplies a normal gene to retinal cells carrying mutations 
  • If approved, it would become the first gene therapy for the treatment of an inherited disease in the U.S.

(CNN)When her son was just 3-months-old, Elizabeth Guardino began to notice that he never responded when she smiled. Dangling a toy in front of his face, Christian did not follow it with his eyes.

"He also started to stare at the sun wide-eyed," said Guardino of Patchogue, New York. "That also shook us quite a bit."
These "triggers" sent her to get Christian's vision tested when he was 6 months old.
    The diagnosis was Leber's congenital amaurosis (LCA), a rare inherited eye disease that causes severe visual impairment beginning in infancy. Scientists have identified at least 13 different types of LCA with separate genetic causes.
    "How it was explained to me is I would have to carry a gene and so would my husband, so it's that rare of an occurrence," said Guardino. Still, there was some hopeful news that day.
    Christian had the type of LCA that would remain stable or slightly improve with age.
    "No one knew what his diagnosis really meant," she recalled. "Including ourselves."
    She clung to the hope that her son's impairment wouldn't worsen with age. As he grew, he developed his natural gift for music, which served as a consolation when he struggled to keep up with friends. However, when Christian reached age 12 or so, Elizabeth started seeing a decline in his vision.
    On Facebook she happened upon an LCA support group. "I thought this cannot be, because it's so, so rare," said Guardino. A family conference in Philadelphia was scheduled for July 2012.
    "We jumped on that bandwagon," she said. Talking to the specialist there, she learned that Christian, 12 at the time, would go completely blind.
    "It took every ounce of strength for me to not go running out of that room screaming. It was devastating," she said.
    Later, when tests confirmed a mutation of the RPE65 gene, she consented to treating Christian with an experimental drug made by Philadelphia-based Spark Therapeutics, Inc.
    Luxturna (voretigene neparvovec), an untried gene therapy, would be her gamble to save what little vision her son still had.

    Drug safety and effectiveness

    "We very much included Christian in that decision because, I mean, that's a heck of a decision for someone to make for another human being when you don't know what the outcome could be," she said. "Christian was gung ho, right from the get-go."
    "Our goal going in was just to stop the progression of the disease, but we wound up getting so much more," she said.
    The life-changing therapy Christian experienced may now be poised to make history.
    On Thursday, a Food and Drug Administration advisory committee will meet to review Luxturna. Outside experts will present research and recommendations on the safety and effectiveness of the treatment for patients with retinal dystrophy caused by a confirmed RPE65 mutation. Patients will also make a case by sharing their personal experiences.
    Monique da Silva, a spokeswoman for Spark Therapeutics explained that the company believes the total "population in the US, Europe and select additional markets in the Americas and Asia/Pacific is up to approximately 6,000 individuals" who have RPE65 mutations. The US National Library of Medicine estimates that LCA occurs in 2 to 3 per 100,000 newborns, though not all of these are RPE65 mutations.
    The public meeting will conclude with a vote on whether or not to recommend the treatment for approval. This will be followed by a decision from the FDA. While the agency frequently follows the recommendations of its advisory committees, it is not required to when making approval decisions.
    A greenlight for Luxturna would be historic. If approved, it would become the first gene therapy for the treatment of an inherited disease in the United States.

    How it works

    Luxturna works by supplying a third gene -- a normal RPE65 gene -- to retinal cells. It is a liquid that is injected directly into the eye with a microscopic needle during a surgical procedure, explained Dr. Vinit B. Mahajan, an associate professor of ophthalmology, Vitreoretinal Surgery and Disease Byers Eye Institute at Stanford University.
    "In those drops of liquid that we're injecting is a gene therapy virus ... a virus that contains a healthy version of the gene," said Mahajan, who was involved in the phase 3 clinical trial of the drug while teaching at the University of Iowa, one of the testing centers for the treatment.
    Essentially then, the drug adds a third version of the gene, a normal version, to the cell, while the two mutated genes causing the disease remain inside the cell as well, explained Mahajan. They are not removed or replaced.