CRISPR-based gene editing holds promise for treating rare blindness

About 79% of clinical trial participants experienced visible improvement after undergoing CRISPR-based gene editing aimed at curing a rare form of blindness, according to a paper published in . New England Medical Journal.

This trial shows that CRISPR gene editing has great potential to treat inherited retinal degenerations. For doctors, there is nothing more rewarding than hearing a patient describe how their vision has improved after treatment. One trial participant's girlfriend shared several examples, including how she was able to find her cell phone after she misplaced it, and how she saw a small light on her coffee machine and knew it was working. Did. These types of tasks may seem trivial to people with normal vision, but such improvements can have a big impact on the quality of life for people with amblyopia. ”

Mark Pennesi, MD, corresponding author of the paper, ophthalmologist, lead scientist of the phase 1/2 BRILLIANCE trial at Oregon Health & Science University, corresponding author of the paper

This study evaluated the safety and efficacy of EDIT-101, an gene editing therapy developed by Editas Medicine using CRISPR technology. This treatment was specifically designed to edit mutations in the body. CEP290 genedescribes steps to create proteins important for vision.

People with this mutation commonly suffer from a rare condition called Leber congenital amaurosis (LCA, type 10), for which there is no cure. Different types of LCA occur in approximately 2 to 3 out of 100,000 total newborns.

OHSU Casey Eye Institute treated the trial's first participants in early 2020. This procedure also marked the first time CRISPR has been used to edit genes within the human body. alive Gene editing.

Today's paper describes the results of the study up to February 2023, and how 14 trial participants (12 adults and 2 children) responded when given EDIT-101 in one eye. Detailed information. The main results are:

• Eleven participants, or about 79%, showed improvement in at least one of the four outcomes measured.
• Six participants, or approximately 43%, showed improvement in two or more outcomes.
• Six participants, or approximately 43%, reported improved vision-related quality of life.
• Four participants, or approximately 29%, showed clinically meaningful improvements in visual acuity, or how well they could identify objects and letters on a chart.
• There were no serious adverse events related to treatment.
• Most adverse events were mild or moderate and all subsequently resolved.

Four specific outcomes were used to evaluate the effectiveness of the treatment.

• Visual acuity, as explained above
• How well participants recognized dots of colored light while looking through a special device, which scientists call a full-field test.
• How well participants navigated a research maze in which physical objects and varying amounts of light were present.
• How many participants reported feeling an improvement in their quality of life?

This is the first time that the results of this trial have been published in a peer-reviewed scientific journal. Previously, interim results were shared through conference presentations by researchers and press releases issued by trial sponsors.

Further research for future treatments

In November 2022, trial sponsor Editas Medicine announced that it would suspend trial enrollment and seek another partner to continue developing the treatment. Pennesi and colleagues are looking to work with Editas and other commercial partners to conduct additional trials. The researchers hope that future studies will consider the ideal dosage, whether treatment effects are more pronounced in certain age groups, such as younger patients, and refine endpoints to measure effects on daily living activities. I hope it includes points.

“This study shows that CRISPR gene therapy for inherited vision loss is worth continued pursuit in research and clinical trials,” said corresponding author Eric Pierce, M.D., an ophthalmologist at Mass Eye. Ta. “Further research is needed to determine who could benefit most, but we think the early results are promising. Some participants said they were finally able to put food on their plates. It was a big deal to hear how excited they were to be able to see again. These were people who couldn't read any lines on the eye chart and needed treatment. I didn't have a choice, and this is the unfortunate reality for most people with inherited retinal diseases. ”

“Our patient was the first congenitally blind child to be treated with gene editing, resulting in significant improvements in daytime vision,” said the paper's third corresponding author. said Thomas S. Aleman, MD, a pediatric ophthalmologist at Children's Hospital and University. from Scheie Eye Institute in Pennsylvania. “Our hope is that this study will pave the way for treatment and further improvement of vision in younger children with similar symptoms. This trial will provide important alternative treatments when traditional symptoms appear. By providing this, we represent a breakthrough in the treatment of a genetic disease, certain hereditary blindness.'' Treatments such as gene enhancement are not an option. ”

“The results of the BRILLIANCE study provide proof of concept and important learnings for the development of new and innovative medicines for inherited retinal diseases. We are confident that CRISPR-based gene editing therapies can be safely delivered to the retina. “We demonstrated clinically meaningful benefits,” said Bison May, M.D., chief medical officer of Editas Medicine.

OHSU Casey Eye Institute was one of five clinical sites that recruited participants for this study. Other sites include: Bascom Palmer Eye Institute, Miami, Florida. Mass Eye and Year, Boston, Massachusetts. University of Pennsylvania Scheie Eye Institute and Children's Hospital of Philadelphia. Kellogg Eye Center in Ann Arbor, Michigan.