In a groundbreaking clinical trial, researchers have successfully demonstrated the safety and efficacy of CRISPR gene editing in treating inherited blindness caused by mutations in the CEP290 gene. The trial, known as BRILLIANCE, involved 14 participants who received a single injection of the CRISPR/Cas9-based medicine, EDIT-101, directly inside the body. This marks the first instance of CRISPR being administered internally, highlighting its potential to correct genetic defects underlying severe visual impairments.

Led by principal investigator Dr. Eric Pierce of Mass Eye and Ear, the trial showed measurable improvements in vision for 11 out of the 14 participants. The participants, including 12 adults and two children, all had a form of Leber Congenital Amaurosis (LCA) caused by mutations in the CEP290 gene. Previous to this trial, they had no available treatment options.

The results, published in The New England Journal of Medicine, support the continued pursuit of CRISPR gene therapy for inherited vision loss. Dr. Pierce emphasized the promising nature of the early findings, mentioning the thrill expressed by participants who could now see things they were previously unable to, such as food on their plates.

Safety was a crucial aspect of the trial, and no serious adverse events were reported. The researchers focused primarily on the safety of the CRISPR/Cas9 treatment, with a secondary analysis for efficacy. The study examined measures such as best-corrected visual acuity, dark-adapted full-field stimulus testing, visual function navigation, and vision-related quality of life. Eleven participants demonstrated improvements in at least one of these measures, while four had clinically meaningful improvement in best-corrected visual acuity.

Dr. Baisong Mei, Chief Medical Officer at Editas Medicine, the sponsor of the trial, expressed optimism about the findings. He stated that the BRILLIANCE trial provides proof of concept and important insights for the development of new and innovative medicines for inherited retinal diseases.

Mutations in the CEP290 gene are the leading cause of inherited blindness during the first decade of life. The CRISPR-Cas9 gene editing toolkit was used to target these mutations, with the aim of restoring the ability to produce the gene and protein responsible for light-sensing cells in the eye's retina.

The trial's success paves the way for potential treatments of younger children with similar conditions. Future studies will explore ideal dosing, the impact on different age groups, and refined endpoints to measure the effects of improved cone function on daily activities.

Although enrollment in the BRILLIANCE trial has been paused, further trials in collaboration with other commercial partners are being considered.

This landmark clinical trial represents a significant advancement in the treatment of genetic diseases, particularly genetic blindness. The use of CRISPR gene editing offers hope for the development of life-changing treatments for patients with inherited retinal disorders, ultimately improving their quality of life and opening new possibilities for treatment.