At Children’s Hospital Los Angeles Dr. Aaron Nagiel, MD, PhD, has witnessed firsthand the profound impact of retinal gene therapy on children with Leber congenital amaurosis (LCA), a rare genetic disorder that causes severe vision loss. Though visual progress is often measurable through eye chart tests, Dr. Nagiel emphasizes that the most moving signs of improvement come from the heartfelt messages he receives from parents long after the treatment.
One message from a parent described their toddler seeing animals at the zoo for the first time, another shared how their young daughter noticed her shadow on the sidewalk. One particularly touching story came from the parents of a 7-year-old who could now read the school blackboard and ride her bike at dusk. These milestones are life-changing for children with LCA, a disease that typically leads to progressive blindness starting with night blindness and poor vision in dim light.
Since 2018, Dr. Nagiel and his team at CHLA’s Vision Center have been treating LCA patients with Luxturna, a groundbreaking gene therapy. After its FDA approval in 2017, CHLA became the first West Coast center to administer this therapy, and recently celebrated performing its 100th retinal gene therapy procedure. The hospital now leads the nation in administering Luxturna.
Why Early Treatment is Essential
LCA causes vision loss that progresses rapidly, with children losing almost all vision by middle age. However, gene therapy like Luxturna has the potential not only to improve vision but also to halt further degeneration of retinal cells. Dr. Nagiel explains that the retina can be compared to a factory that cannot function because a tiny, essential tool is missing. Luxturna works by restoring that tool, allowing the retina to begin functioning again. Early treatment is crucial because if therapy is delayed too long, the “factory” could shut down completely.
How Luxturna Works
Gene therapy like Luxturna offers a revolutionary way to treat genetic diseases by making permanent changes with a single procedure. Luxturna delivers a healthy copy of the mutated RPE65 gene inside a viral vector, which acts as a carrier to transfer the gene into retinal cells. Once the gene is functional, the cells can produce healthy proteins, enabling proper retinal function. This one-time treatment can have lasting effects, potentially improving vision for a patient’s lifetime.
Who is Eligible for Luxturna?
Patients eligible for Luxturna must be over 12 months old and diagnosed with mutations in both copies of the RPE65 gene. Since over 300 genes can cause retinal degenerations, CHLA’s Center for Personalized Medicine plays a critical role in confirming the specific genetic mutations before treatment.
The Procedure
The Luxturna procedure is delicate and highly specialized. First, a vitrectomy is performed, a standard retinal technique. Then, using both his hands and feet, Dr. Nagiel delivers the gene therapy under the retina. The medication must be kept at extremely cold temperatures and prepared with precision, requiring a coordinated effort from the pharmacy and anesthesia teams.
During the procedure, Dr. Nagiel controls an advanced microscope with his left foot and adjusts the medication delivery with his right foot. This intricate process allows for the precise placement of the gene therapy into the retina.
Early Results and Success Stories
Some patients experience significant improvements in vision within the first week of treatment. Many children who had previously been unable to see objects like fish in a tank or birds in the sky begin to notice these details. One memorable moment came when a mother sent a picture of her daughter seeing her shadow for the first time.
Parents have shared stories of their children no longer being night-blind and gaining the confidence to do everyday activities like reading, going trick-or-treating, or riding bikes in the evening.
While clinical tests can’t always capture these emotional milestones, the feedback from parents about their children seeing things they had never seen before is invaluable.
The Future of Retinal Gene Therapy
CHLA continues to recruit patients for several clinical trials aimed at advancing the field of gene therapy. As awareness and access to this treatment expand, more children will receive gene therapy at an early age, preventing vision loss before it happens. Dr. Nagiel hopes that in the next decade, gene therapies will be routinely used to treat children at the onset of retinal diseases, ensuring life-changing improvements in vision from a young age.
With each new success story and milestone, CHLA’s retinal gene therapy program brings hope to children with LCA and other retinal diseases, offering them a brighter future filled with vision and possibilities.
