CRISPR Therapy Warrants Further Study for Inherited Retinal Diseases


Nine of 14 participants receiving EDIT-101 had meaningful improvements in at least 1 key functional outcome.

Eric Pierce, MD, PhD, director, Ocular Genomics Institute and Berman-Gund Laboratory for the Study of Retinal Degenerations, Mass Eye and Ear, Harvard Medical School, and Mass General Brigham healthcare system

Eric Pierce, MD, PhD

Credit: Mass Eye and Ear

EDIT-101 (Editas Medicine), an in vivo, CRISPR/Cas9 gene therapy, improved photoreceptor function in study participants with inherited retinal degenerations due to the IVS26 variant of centrosomal protein 290 (CEP290), also known as Leber’s congenital amaurosis, according to a paper published on the phase 1/2 BRILLIANCE trial (NCT03872479).1

“This research demonstrates that CRISPR gene therapy for inherited vision loss is worth continued pursuit in research and clinical trials,” principal investigator Eric Pierce, MD, PhD, director, Ocular Genomics Institute and Berman-Gund Laboratory for the Study of Retinal Degenerations, Mass Eye and Ear, Harvard Medical School, and Mass General Brigham healthcare system, said in a statement.2 “While more research is needed to determine who may benefit most, we consider the early results promising. To hear from several participants how thrilled they were that they could finally see the food on their plates –that is a big deal. These were individuals who could not read any lines on an eye chart and who had no treatment options, which is the unfortunate reality for most people with inherited retinal disorders.”

The BRILLIANCE trial administered EDIT-101 to 14 participants, 12 adults with a median age of 37 years (range, 17 to 63), and 2 children aged 9 and 14 years with CEP290-associated inherited retinal degeneration caused by a homozygous or compound heterozygous IVS26 variant. The participants received a subretinal injection of EDIT-101 in the worse (study) eye at either a low (n = 2), intermediate (n = 7, including 2 children), or high dose (n = 5).1

“Our patients are the first congenitally blind children to be treated with gene editing, which significantly improved their daytime vision,” the paper’s third corresponding author, Tomas S. Aleman, MD, pediatric ophthalmologist, Children’s Hospital of Philadelphia and Scheie Eye Institute, University of Pennsylvania, said in another statement.3 “Our hope is that the study will pave the road for treatments of younger children with similar conditions and further improvements in vision. This trial represents a landmark in the treatment of genetic disease, in specific genetic blindness, by offering important alternative treatment when traditional forms of therapy, such as gene augmentation, are not an option.”

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Investigators did not observe any serious adverse events related to treatment or procedure, or any dose-limiting toxicities. Most adverse events were mild (76%) or moderate (22%), and 41% were related to the procedure.1

At baseline, participants had a median best corrected visual acuity (BCVA) in the study eye of 2.4 log10 of the minimum angle of resolution (range, 3.9 to 0.6); 9 participants (64%) had meaningful improvements in BCVA, full-field stimulus test (FST), or mobility test scores. With a median follow-up of 376 days (interquartile range, 193 to 454) as of February 2023, meaningful improvements in FST were observed in 6 participants including both children, 5 of whom had improvements in at least 1 other key secondary outcome. Overall, 11 participants (79%) had improvement in at least 1 of 4 key efficacy outcomes, whereas 6 (43%) had improvement in 2 or more outcomes. Six participants also had meaningful improvements from baseline in vision-related quality of life scores.1 

“This trial shows CRISPR gene editing has exciting potential to treat inherited retinal degeneration,” corresponding author Mark Pennesi, MD, PhD, ophthalmologist and lead scientist on the trial, Oregon Health & Science University, added.3 “There is nothing more rewarding to a physician than hearing a patient describe how their vision has improved after a treatment. 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.”

1. PIerce EA, Aleman TS, Jayasundera KT, et al. Gene Editing for CEP290-Associated Retinal Degeneration. New Eng J Med. 2024. Published online May 6, 2024. doi: 10.1056/NEJMoa2309915
2. CRIPSR gene editing leads to improvements in vision for people with inherited blindness, clinical trial shows. News release. Mass Eye and Ear. May 6, 2024.
3. Participants of pioneering CRISPR gene editing trial see vision improve. News release. Oregon Health & Science University.
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