CRISPR gene-editing has improved the vision of patients with an inherited form of blindness, according to results of a Phase 1/2 clinical trial. The results not only give new hope to patients with the condition, but show that CRISPR could be put to use in humans to treat a range of conditions.
Leber Congenital Amaurosis (LCA) is a rare condition that affects about one in every 40,000 newborns. Those affected have a genetic mutation that results in severely reduced vision, leading to complete blindness in about a third of patients. Currently, there are no FDA-approved treatment options at all.
But that might be about to change. The BRILLIANCE trial has been investigating using CRISPR to edit the CEP290 gene, one of the main culprits behind LCA, in 14 patients. The gene-editing treatment is delivered directly to the light-sensitive cells behind the retina, making this the first time CRISPR had been put to work directly in the human body.
Now, the team has detailed the results from the first three years of the trial, from 2020 to 2023. Each patient received the treatment in one eye, and were then monitored for four different outcomes: identifying objects and letters on a chart; how well they could see colored points of light in a full-field test; how well they could navigate a maze with physical objects and different light levels; and their own reported experiences of quality of life changes.
Of the 14 participants, 11 (79%) showed improvement in at least one of those four outcomes, while six (43%) improved in two or more outcomes. Six also reported better quality of life thanks to vision improvements, while four (29%) showed clinically meaningful improvement in the eye chart tests.
“There is nothing more rewarding to a physician than hearing a patient describe how their vision has improved after a treatment,” said Mark Pennesi, corresponding author of the study. “One of our trial participants has shared several examples, including being able to find their phone after misplacing it and knowing that their coffee machine is working by seeing its small lights. While these types of tasks might seem trivial to those who are normally sighted, such improvements can have a huge impact on quality of life for those with low vision.”
No serious adverse effects were observed, and the mild to moderate ones were all resolved. The study suggests that CRISPR can be effective and safe not only for LCA, but potentially other forms of blindness or genetic diseases in general.
The research was published in the New England Journal of Medicine.
Source: OHSU
