Gene therapy has given people with a rare genetic condition that causes them to lose much of their sight early in childhood 100 times better vision. Some patients saw their vision improve by 10,000 times after receiving the highest dose of the treatment for the genetic mutation that causes the disease.
Researchers from the Perelman School of Medicine at the University of Pennsylvania in the United States co-led the human trial, the results of which were published in The Lancet on September 7.
“This 10,000-fold improvement is similar to a patient being able to see their surroundings on a moonlit outdoor night, rather than needing bright indoor lighting like they did before treatment,” said study author Arthur Sedichian, MD, associate professor of ophthalmology and co-director of the Center for Genetic Retinal Diseases. “One patient reported that for the first time, he was able to navigate in the middle of the night outdoors using only the light of a campfire.”
Fifteen people took part in the trial, including three children. Each patient had a mutation in the gene GUCY2D, which led to a condition called Leber congenital amaurosis. Leber is the scientist who first described the condition. The condition, which affects fewer than 100,000 people worldwide, causes significant vision loss from early childhood.
Leber congenital blindness
According to the American Society of Retina Specialists website, Leber congenital amaurosis refers to a group of diseases that cause severe vision loss in early childhood. Vision loss occurs as a result of a malfunction of the retina, the layer at the back of the eye that captures images, much like film in a camera. In Leber congenital amaurosis, the light-sensing cells in the retina do not function properly, resulting in the inability to capture images.
Leber congenital amaurosis is inherited through genes, and there are at least 19 different genetic mutations that can be passed on and cause Leber congenital amaurosis. The affected genes are the ones that give the body instructions to make proteins necessary for vision.
Study and its results
All of the participants had severe vision loss, with their best vision measured at or worse than 20/80, meaning that if a person with normal vision could see an object clearly at 80 feet (about 24 meters) away, these patients had to get as close as 20 feet (about 6 meters) to see it. Glasses offered limited benefit to these patients, because they corrected abnormalities in the eye’s visual ability, but were unable to address medical causes of vision loss such as genetic diseases of the retina such as Leber congenital amaurosis.
The trial tested different dose levels of a gene therapy, called ATSN-101, which was developed from a microorganism and surgically injected under the retina.
In the first part of the study, groups of 3 adults received different doses: low, medium, and high, and patient safety was assessed between each dose level before increasing to the next group. The second part of the study involved only giving the high doses to both the adult and pediatric groups again after safety reviews for the previous groups.
Improvement was noted rapidly, often within the first month of treatment, which lasted for at least 12 months, and of the nine patients who received the maximum dose, two achieved a 10,000-fold improvement in vision.
“Although we previously predicted that vision could be dramatically improved in patients with Leber congenital amaurosis, we did not know how well the patients’ photoreceptors would respond to treatment after decades of blindness,” Sedichian said, according to Science Daily. “It is very satisfying to see a trial conducted in several locations successfully showing that gene therapy can be so effective.”