Two CHOP Patients with an Inherited Blindness Successfully Treated with Gene Editing

A multi-institutional clinical trial involving researchers from Children’s Hospital of Philadelphia (CHOP) and the Scheie Eye Institute at the University of Pennsylvania found that CRISPR-Cas9 gene editing delivered to fourteen individuals with a form of inherited blindness was safe and led to measurable improvements in vision in nearly half of the of the participants treated, including the two children treated at CHOP. The findings were published today in the New England Journal of Medicine.

The phase 1/2 BRILLIANCE clinical trial included 12 adults and two children who were born with a form of Leber Congenital Amaurosis (LCA) caused by mutations in the CEP290 gene. Mutations in the CEP290 gene are the leading cause of inherited blindness that takes place during the first year of life. The mutations cause rod and cone photoceptors in the eye’s retina to function improperly, which after some time will lead to irreversible vision loss.

The participants underwent a single injection of a CRISPR/Cas9 genome editing medicine, EDIT-101 (manufactured by Editas Medicine, Inc.) in one eye via a specialized surgical procedure. This trial, the first to deliver CRISPR-based experimental medicine to the eye, focused primarily on safety with a secondary analysis for efficacy. Participants were monitored every three months for at least six months at the time of the report with follow-ups ongoing.

The study found no reported treatment or procedure-related adverse events or dose-limiting toxicities. For efficacy, the researchers looked at four measures: best-corrected visual acuity (BCVA); dark-adapted full-field stimulus testing (FST), visual function navigation (VNC, as measured by a maze participants completed), and vision-related quality of life.

Eleven participants demonstrated improvements in at least one of those outcomes, while six demonstrated improvement in two or more. Six participants experienced meaningful improvements in cone-mediated vision as indicated by FSTs, five of whom had improvements in at least one of the three other outcomes.

“Our patients are the first congenitally blind children to be treated with gene-editing, which significantly improved their daytime vision. Our hope is that the study will pave the road for treatments of younger children with similar conditions and further improvements in vision,” said Tomas S. Aleman, MD, the Irene Heinz-Given and John LaPorte Research Professor in Ophthalmology at Penn Medicine with the Scheie Eye Institute and a pediatric ophthalmologist at CHOP who served as a site principal investigator and study co-author. “This trial represents a landmark in the treatment of genetic diseases, in specific, genetic blindness, by offering an important alternative treatment, when traditional forms of gene therapy, such as gene augmentation, are not an option.”

This research trial was conducted in collaboration with the Clinical In Vivo Gene Therapy group at CHOP, a multidisciplinary team of experts committed to advancing transformative human therapies and building upon CHOP’s legacy as a leader in breakthrough gene therapy.

This research was funded by Editas medicine. This research was also supported by the National Institute of Health P30 EY014104 core grant to Mass Eye and Ear, P30 EY010572 core grant, the Malcolm M. Marquis MD Endowed Fund for Innovation, and an unrestricted grant from Research to Prevent Blindness to Casey Eye Institute and by the Paul and Evanina Mackall Foundation Trust to the Scheie Eye Institute. 

Pierce, EA et al. “Gene-editing for CEP290-associated Retinal Degeneration.” NEJM DOI: 10.1056/NEJMoa2309915