According to an article published in the New England Journal of Medicine, around 79% of clinical trial participants saw quantifiable improvement after receiving experimental, CRISPR-based gene editing intended to correct a rare form of blindness.
This trial shows CRISPR gene editing has exciting potential to treat inherited retinal degeneration.
a corresponding author on the paper, an ophthalmologist and Oregon Health & Science University’s lead scientist for the phase 1/2.
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.
While these types of tasks might seem trivial to those who are normally sighted, such improvements can have a huge impact on quality of life for those with low vision.
Mark Pennesi, M.D., Ph.D.
The CRISPR technology-based experimental gene editing medication EDIT-101, created by Editas Medicine, was tested for safety and efficacy in the BRILLIANCE study. The goal of the experimental treatment was to correct a mutation in the CEP290 gene, which codes for a protein essential to vision.
Leber Congenital Amaurosis, or LCA, Type 10, is an uncommon disorder that affects people who carry this gene mutation. At this time, there is no FDA-approved therapy for this ailment. There are two or three cases of LCA per 100,000 infants.
Early in 2020, the first patient in the experiment received care at the OHSU Casey Eye Institute. Additionally, that process was the first instance of CRISPR being utilised for “in vivo” gene editing—editing genes within the human body.
The latest study outlines the trial’s results up to February 2023 and how its 14 participants 12 adults and 2 children reacted to receiving EDIT-101 in one eye. Important outcomes consist of:
- 11 participants, about 79%, showed improvement in at least one of four measured outcomes.
- 6 participants, about 43%, showed improvement in two or more outcomes.
- 6 participants, about 43%, reported improved vision-related quality of life.
- 4 participants, about 29%, had clinically meaningful improvement in visual acuity, or how well they could identify objects or letters on a chart.
- There were no serious adverse events related to the treatment.
- Most adverse events were mild or moderate, and all have since been resolved.
Four specific outcomes were used to evaluate the experimental treatment’s effectiveness:
- Visual acuity
- How well participants saw coloured points of light while looking into a specialized device, which scientists call a full-field test
- How well participants navigated a research maze with physical objects and varying amounts of light
- How many participants reported experiencing improved quality of life
Trial sponsor Editas Medicine declared in November 2022 that it would be stopping the trial’s recruitment and looking for a new partner to carry on the development of the investigational medicine. In cooperation with Editas, Pennesi and associates are looking at conducting more trials with various business partners. Future studies, according to the researchers, should look at the optimal dosage, if a therapy’s effects are more noticeable in younger individuals, and include more precise endpoints to gauge how the treatment affects everyday activities.
This research demonstrates that CRISPR gene therapy for inherited vision loss is worth continued pursuit in research and clinical trials,
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.
Eric Pierce, M.D., Ph.D
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. 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.
Tomas S. Aleman, M.D.
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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 have clinically meaningful outcomes.
Baisong Mei, M.D., Ph.D
The experiment involved participant recruitment from five clinical sites, including the OHSU Casey Eye Institute. The other locations are Kellogg Eye Centre in Ann Arbour, Michigan; Scheie Eye Institute at the University of Pennsylvania and Children’s Hospital of Philadelphia; Mass Eye and Ear in Boston, Massachusetts; and Bascom Palmer Eye Institute in Miami, Florida.
Source: Oregon Health & Science University News
Journal Reference: Pierce, Eric A., et al. “Gene Editing for CEP290-Associated Retinal Degeneration.” New England Journal of Medicine (2024). DOI: 10.1056/NEJMoa2309915
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