Doctors awarded science ‘Oscar’ for curing inherited blindness with gene therapy

It began with a phone call from a lab technician: "They can see!"

The dogs, blind since birth and once stumbling through obstacle courses, suddenly twirled and moved around easily with their newly restored eyes. That call, decades ago, was the first sign that a bold idea two physician-scientists had imagined in medical school could actually work.

Jean Bennett, Albert Maguire, and Katherine High received the Breakthrough Prize in Life Sciences, often called science's version of the Academy Awards.

They were honored for their idea and the 40 years of work it took to create Luxturna, the world's first FDA-approved gene therapy for an inherited disease.

Three scientists, one vision

Bennett, 71, and Maguire, 66, are married emeritus professors of ophthalmology at the University of Pennsylvania's Perelman School of Medicine. They met as students at Harvard Medical School, where they were paired together to dissect a brain.

High, 74, is a former emeritus professor of pediatrics at the Children's Hospital of Philadelphia (CHOP) and is now CEO of RhyGaze, a gene therapy company.

While Bennett and Maguire were developing their therapy, High was working on a similar path at CHOP, focusing on gene therapy for hemophilia, a life-threatening bleeding disorder. She showed long-term disease reversal in dogs and moved into early human trials.

The disease they set out to beat

Leber Congenital Amaurosis, or LCA, is a rare inherited retinal disease caused by mutations in the RPE65 gene, which produces a protein critical to the visual cycle — the biological process by which the retina responds to light.

Children born with faulty copies of this gene can typically detect only very bright light at birth. Most progress to complete blindness by early adulthood, often before their 20s, and sometimes as early as kindergarten.

When Bennett and Maguire started their work in the early 1990s, only a few retinal disease genes had been identified. The technology to treat them was not available yet.

They spent about ten years developing the basic tools, learning how to deliver a corrected gene into retinal cells using a modified virus as the carrier, and how to measure the results.

Their first test subjects were blind dogs housed at the University of Pennsylvania School of Veterinary Medicine, whose condition was very similar to human LCA.

They injected the experimental therapy into one eye of each of three dogs. The call from the lab technician came soon after. Two of those dogs, Venus and Mercury, later became the couple's pets.

What the trials showed

The results from 37 eligible clinical trial participants were remarkable. Seventy-two percent reported the greatest possible improvement on a standard test of low-light vision, which simulates night conditions. Many also gained both peripheral and central vision.

One patient who had previously been able to detect only changes in light became capable of walking unaided through Philadelphia at night and could make out the clock on City Hall. Another saw a star for the first time in her life, six days after the procedure.

In 2017, the therapy, then developed by Spark Therapeutics, a company spun out from CHOP, was approved by the U.S. Food and Drug Administration under the name Luxturna. It was the first time the FDA approved a gene therapy for any inherited disease.

A foundation for the entire field

The impact of this work goes far beyond LCA. According to Penn Medicine, the therapy has paved the way for more than 140 gene therapy trials for retinal conditions, including macular degeneration and diabetic retinopathy. These diseases together affect about 30 million people in the U.S. Another 80 trials are now underway. A separate treatment based on High's hemophilia research received its own FDA approval in 2024.

For Bennett, Maguire, and High, this recognition marks the end of what they called a difficult journey through a field that sometimes seemed to be falling apart around them.