For many it would have been an ordinary scene. But as Munira Yamani watched her 7-year-old daughter Ruqaiyah move through their Conroe kitchen, turning on the oven to preheat and pulling out ingredients to bake a cake without any help, she marveled at what her youngest daughter, who had been going blind since she was a baby, could do on her own. “She was baking a cake for her grandma. She didn’t want help, and I could see she didn’t need it. She could see,” Munira recalls. “It was one of the best cakes I’ve ever tasted.”
There was a time when even the easiest tasks—picking Legos up off the floor, walking through a dimly lit room without stumbling—were nearly impossible for Ruqaiyah. When she was just 4 months old, her parents had noticed that her eyes didn’t seem to be focusing properly. After appointments with numerous doctors, a specialist at Baylor College of Medicine diagnosed Ruqaiyah with Leber Congenital Amaurosis, an inherited disease in which a mutation of the gene known as RPE65 causes the shortage of a protein with a key function: translating light into electrical signals that the brain can understand. Without it, patients start to lose their sight in childhood, becoming legally blind by the time they are teenagers.
In 2012, when Ruqaiyah was less than a year old, she began working with state-provided teachers to develop the skills she would need to live with limited sight. But her parents were already hearing there might be another option. Dr. Timothy Stout, chair of ophthalmology and director of the Cullen Eye Institute at Baylor, just a drive away in the heart of the Texas Medical Center, was performing clinical trials for a possible treatment on patients 3 and older. “We knew if there was something to be done, we would do it,” Ruqaiyah’s father, Hussein Yamani, says.
Since his med student days at Baylor, Stout had been researching ways to use viruses to transport useful information to cells. After becoming an ophthalmologist, he decided to try to combine that research with gene-therapy advances to treat eye diseases like LCA. “There were all of these devastating diseases that cause blindness in little kids, and I thought this would be the perfect place to test out gene therapy,” he says. “I thought that maybe we could put these therapeutic genes into viruses and make kids better.”
Working with a half dozen doctors and researchers across the country, Stout figured out how to insert copies of the RPE65 gene into the Adeno-associated virus—chosen for its small size, excellent carrying capacity, and general harmlessness—with the idea that, in surgery, doctors would remove the vitreous, clear fluid behind the retina and replace it with fluid full of the gene-loaded virus. Clinical trials, launched in 2007, found that while the treatment wasn’t as effective for adults, children with LCA saw vast improvements. And for the youngest patients, the results were staggering.
“Watch this,” Stout says as he pulls up a video on his iPad. A little boy wearing an eye patch tosses a baseball into the air. “We have all kinds of tests to show how the treatment has worked, but there’s nothing compared to a mom with a smartphone. With his untreated eye, he can’t catch the ball. But with his treated eye …” Stout taps the screen, and the video shows the boy, now using his other eye—surgeons operate on one at a time—catching the ball.
In December 2017 the FDA approved Luxturna—an RPE65-loaded fluid manufactured by Spark Therapeutics, based on the work of Stout and his collaborators—making it the first FDA-approved gene therapy treatment in the country. And suddenly children diagnosed with LCA had options.
“When I finished my fellowship on retina surgery in 2016, the main teaching was still that there was really nothing we could do to help patients with these types of conditions,” says Dr. Tahira Scholle, assistant professor of ophthalmology at Baylor, where she’s one of three doctors who perform the procedure. “But once this hit the market that changed, almost overnight. We could do something for them now.”
Since Ruqaiyah had missed the chance to participate in Stout’s clinical trials, turning 3 after they were over, her parents had to wait for FDA approval to go forward. It was last fall that the girl, then 6, finally underwent the surgeries. At the time she was learning to use a cane, and aides would guide her through school every day. But within weeks she required fewer services. “She could go from her class to the library and to the cafeteria without any help at all,” Hussein says. “She didn’t want help, because she’s very independent. You never know what the future holds, but I never thought this would be possible.”
After Ruqaiyah’s surgery, her mother realized she was no longer nervous about her youngest daughter. Munira has even gone back to work, taking a part-time job in digital marketing. “It’s changed our lives, all of our lives. She can take care of herself, dress herself. And when she goes outside I’m not worried anymore, her siblings aren’t as worried, because she can see,” Munira says. “It’s like a miracle. It is a miracle.”