“This research demonstrates that CRISPR gene therapy for inherited vision loss is worth continued pursuit in research and clinical trials,” said Pierce, director of the Ocular Genomics Institute and Berman-Gund Laboratory for the Study of Retinal Degenerations at Mass Eye and Ear and Harvard Medical School. “While more research is needed to determine who may benefit most, we consider the early results promising. Hearing from several participants about their excitement at finally being able to see the food on their plates is a significant milestone.”

The clinical trial involved 14 participants, including 12 adults (ages 17 to 63) and two children (ages 10 and 14), all born with a form of Leber Congenital Amaurosis (LCA) caused by mutations in the centrosomal protein 290 (CEP290) gene. They received a single injection of a CRISPR/Cas9 genome editing medicine, EDIT-101, in one eye through a specialized surgical procedure. This trial, which marked the first time a CRISPR-based investigational medicine was administered directly inside the body, primarily assessed safety while also evaluating efficacy.

No serious treatment or procedure-related adverse events were reported, nor were there any dose-limiting toxicities. The researchers assessed four measures for efficacy: best-corrected visual acuity (BCVA), dark-adapted full-field stimulus testing (FST), visual function navigation (VNC, measured by a maze participants completed), and vision-related quality of life.

Eleven participants demonstrated improvements in at least one of these outcomes, while six showed improvement in two or more measures. Four participants had clinically meaningful improvement in BCVA. Six participants experienced significant improvements in cone-mediated vision as indicated by FSTs, five of whom also improved in at least one other outcome. Cone photoreceptors are critical for daytime and central vision.

“The results from the BRILLIANCE trial provide proof of concept and important learnings for the development of new and innovative medicines for inherited retinal diseases. We’ve demonstrated that we can safely deliver a CRISPR-based gene editing therapeutic to the retina and achieve clinically meaningful outcomes,” said Baisong Mei, MD, PhD, Chief Medical Officer at Editas Medicine.

Studies like this highlight the promise of gene therapy for treating previously incurable conditions. Mass General Brigham’s Gene and Cell Therapy Institute is working to translate scientific discoveries into first-in-human clinical trials and, ultimately, life-changing treatments for patients.

Mutations in the CEP290 gene are the leading cause of inherited blindness during the first decade of life. These mutations cause rod and cone photoreceptors in the retina to malfunction, eventually leading to irreversible vision loss. Pierce compares it to a small part of an engine breaking down, causing the entire engine to fail over time. CRISPR-Cas9, a gene editing toolkit, acts as a GPS-guided scissor to cut out the mutated portion of the genome, allowing a functional gene to be expressed.

The goal of the treatment for inherited blindness was to inject CRISPR into the retina to restore the ability to produce the gene and protein responsible for light-sensing cells. The CEP290 gene is larger than what traditional adeno-associated virus (AAV) vector gene therapies can accommodate, making CRISPR a suitable alternative for this specific application.

The continued research and clinical trials will focus on further understanding the treatment’s efficacy and determining the best candidates for this groundbreaking therapy.

By Impact Lab