CRIPSR gene editing leads to improvements in vision for people with LCA10, clinical trial shows

Key Takeaways

• About 79% of clinical trial participants experienced measurable improvement after receiving experimental, CRISPR-based gene editing that is designed to fix a rare form of inherited blindness called Leber Congenital Amaurosis, Type 10 (LCA10), according to a new article.
• The trial shows CRISPER gene editing has exciting potential to treat inherited retinal degeneration.

Results from a clinical trial of CRISPR gene editing in 14 individuals with a form of inherited blindness show that the treatment is safe, and led to measurable improvements in 11 of the 14 participants treated. The Phase I/II trial, called BRILLIANCE, which was focused primarily on safety with a secondary analysis for efficacy, tested the new therapy on 12 adults (ages 17 to 63) and two children (ages 10 and 14) who were born with Leber Congenital Amaurosis, Type 10 (LCA10). Findings were reported May 6 in The New England Journal of Medicine. 

LCA10 is caused by mutations in the centrosomal protein 290 (CEP290) gene, which provides instructions to create a protein that is critical for sight. The CEP290 gene is larger than what traditional adeno-associated virus (AAV) vector gene therapies, including one FDA-approved for a different type of inherited vision loss, can accommodate. Therefore, the researchers used CRISPR-Cas9, a gene editing toolkit that acts like a GPS-guided scissor to cut a portion of the mutated genome to leave a functional gene. This trial included the first patient to ever receive a CRISPR-based investigational medicine directly inside the body.  “This research demonstrates that CRISPR gene therapy for inherited vision loss is worth continued pursuit in research and clinical trials,” said principal investigator Eric Pierce, MD, Ph.D., of Mass Eye and Ear, a member of the Mass General Brigham health care system. “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.”

Corresponding author Mark Pennesi, MD, Ph.D., from Oregon Health & Science University (OHSU), added, “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.”

In November 2022, Editas, the maker of the therapy, paused enrollment on the BRILLIANCE trial. The researchers are exploring working with other commercial partners to conduct additional trials, in collaboration with Editas. They hope future studies can examine ideal dosing, determine whether a treatment effect is more pronounced in certain age groups such as younger patients and include refined endpoints to measure the effects of the therapy on activities of daily living.

For more information on this trial, visit https://clinicaltrials.gov/study/NCT03872479.

Edited by Miriam Kaplan, PhD

Sources:

Massachusetts Eye and Ear Infirmary, “CRIPSR gene editing leads to improvements in vision for people with inherited blindness, clinical trial shows.” Medical Xpress, May 6, 2024; see source article

Oregon Health and Science University, “Participants of pioneering CRISPR gene editing trial see vision improve.” ScienceDaily, May 6, 2024; see source article