Summary: The BRILLIANCE clinical trial has shown that a CRISPR/Cas9-based medicine, EDIT-101, can be safely delivered inside the eye and produced measurable vision improvements for people born with an inherited form of blindness due to mutations in the CEP290 gene. In this early-phase study, 14 participants received a single subretinal injection and 11 demonstrated improvement on at least one vision measure.
BRILLIANCE represents the first in vivo use of CRISPR gene editing to treat inherited retinal disease. The trial’s results provide an initial proof of concept that precise genome editing applied directly to the retina can be safe and lead to clinically meaningful gains in visual function for some patients with Leber congenital amaurosis (LCA) caused by CEP290 mutations.
Key Facts:
- Pioneering in vivo approach: BRILLIANCE is the first clinical trial to deliver CRISPR gene editing directly into the human body to treat inherited blindness, targeting pathogenic variants in the CEP290 gene.
- Clinical improvements observed: Eleven of 14 participants experienced measurable improvements in vision on one or more efficacy assessments, including visual acuity, light sensitivity, navigation testing, and vision-related quality of life.
- Safety profile: No serious treatment- or procedure-related adverse events or dose-limiting toxicities were reported in this trial.
Source: Mass Eye and Ear
The phase 1/2 BRILLIANCE trial was led by Eric Pierce, MD, PhD, of Mass Eye and Ear and sponsored by Editas Medicine, Inc. Its primary goal was to evaluate safety; secondary analyses assessed early signs of efficacy. The trial outcomes were reported May 6 in The New England Journal of Medicine.
All 14 participants—12 adults (ages 17 to 63) and two children (ages 10 and 14)—were born with LCA caused by pathogenic variants in the CEP290 gene. Each participant received a single injection of EDIT-101 into one eye via a specialized surgical procedure. EDIT-101 uses CRISPR-Cas9 genome editing to remove or correct the mutated portion of CEP290 so that retinal cells can resume producing the functional protein essential for light-sensing.
Safety monitoring found no serious adverse events attributed to the treatment or procedure, and no dose-limiting toxicities. Efficacy was evaluated across four main measures: best-corrected visual acuity (BCVA), dark-adapted full-field stimulus testing (FST) to assess rod- and cone-mediated light sensitivity, a vision-related navigation task (VNC maze), and patient-reported vision-related quality of life.
Eleven participants improved on at least one outcome measure; six improved on two or more. Four participants achieved clinically meaningful gains in BCVA. Six participants showed significant improvements in cone-mediated vision on FST, and five of those also improved on one or more other outcome metrics. Improvements in cone photoreceptor function are particularly important because cones support daytime and central vision critical for activities such as reading and identifying objects.
Investigators and sponsors emphasize the encouraging nature of these early results while noting that more research is required to determine optimal dosing, the age groups most likely to benefit, and how best to measure functional gains in daily activities. Enrollment in BRILLIANCE was paused in November 2022; the study team is exploring collaboration with additional partners to advance further trials.
The first in vivo CRISPR treatment in this program was administered at the Casey Eye Institute (OHSU), followed by the initial Mass Eye and Ear patient in September 2020 after pandemic-related delays. Other participating sites included Bascom Palmer Eye Institute, W.K. Kellogg Eye Center, Scheie Eye Institute at the Children’s Hospital of Philadelphia (CHOP), and the Hospital of the University of Pennsylvania.
Dose groups included two adults who received a low dose, five who received a mid dose, five who received a high dose, and two children who received a mid dose at CHOP. Participants were evaluated every three months for the first year and then at less frequent intervals for up to two additional years, with serum testing and comprehensive vision assessments at each visit.
Investigators highlighted patient-reported improvements in everyday tasks—such as locating a misplaced phone or noticing indicator lights on household appliances—as examples of how even modest gains in vision can substantially improve quality of life for people with severe congenital visual impairment.
Authorship and disclosures: The senior corresponding author was Eric A. Pierce, MD, PhD (Mass Eye and Ear). Co-corresponding authors included Tomas S. Aleman, MD (CHOP) and Mark E. Pennesi, MD, PhD (OHSU). Additional authors represented clinical sites and Editas Medicine. Disclosure forms and the full NEJM article provide detailed author disclosures. Funding was provided by Editas Medicine and supported by grants and endowments including NIH core grants to participating institutions and unrestricted grants from Research to Prevent Blindness.
About this CRISPR and vision research news
Author: Ryan Jaslow
Source: Mass Eye and Ear
Contact: Ryan Jaslow – Mass Eye and Ear
Image: The image is credited to Neuroscience News
Original Research: The findings are reported in The New England Journal of Medicine.