CRISPR-based gene editing treatment shows promise for rare eye disorder

By Staff 7 Min Read

  • Researchers from Oregon Health & Science University are using an experimental CRISPR-based gene editing treatment for participants with a rare eye disease that impairs vision.
  • The treatment resulted in significant improvements in vision-related outcomes, such as visual acuity.
  • These results may have the potential for future treatments for a rare disease with few options.

Since its discovery in 2013, researchers have been examining the use of CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) gene editing to treat various health conditions.

Studies have shown CRISPR gene editing may hold promise for treating:

Now, researchers from Oregon Health & Science University are using an experimental CRISPR gene editing treatment to treat an inherited retinal disease called Leber Congenital Amaurosis (LCA), for which there is currently no FDA-approved treatment.

The study was recently published in The New England Journal of Medicine.

LCA is a rare genetic eye disorder that normally presents during the first year of life. The disease affects the retina of the eye, which is the area that tells the brain what you’re seeing.

People with LCA will have low vision and sometimes blindness. LCA is the leading cause of inherited blindness in children, affecting 2–3 infants per 100,000 births worldwide.

“This [is] a blinding disease with no treatments,” Mark Pennesi, MD, PhD, professor of ophthalmology at Oregon Health & Science University, investigator on the Phase 1/2 BRILLIANCE trial, and co-corresponding author of this study, told Medical News Today.

“(This) is an enormous burden on patients (due) to their vision loss.”

LCA is an inherited disease caused by a mutation in specific genes carried by and passed down through a parent.

One of the most common genetic mutations for LCA occurs in the CEP290 gene. One of the roles of the CEP290 gene is to create a protein required for vision.

“Patients with this mutation have profound vision loss with many patients only able to distinguish light [at] birth,” Pennesi explained. “Some patients have better vision but (lose) this over time.”

The Phase 1/2 BRILLIANCE clinical trial tested an experimental CRISPR-based gene editing treatment called EDIT-101, developed by Editas Medicine. The treatment is designed to edit a mutation in the CEP290 gene.

“Gene editing uses CRISPR/CAS proteins, which are like scissors that allow us to make small cuts in the DNA and remove mutations that would otherwise create an abnormal protein,” Pennesi detailed.

Researchers recruited 14 study participants — 12 adults and two children — for the Phase 1/2 BRILLIANCE trial. All participants received EDIT-101 in one eye.

Pennesi and his team measured the success of the treatment through four specific outcomes:

  • visual acuity
  • participants’ ability to see colored points of light during a full-field test
  • ability to navigate a research maze with physical objects and varying amounts of light
  • improved quality of life

At the study’s conclusion, 11 of the 14 participants, or 79%, showed improvement in at least one of the four measured outcomes, while six, or 43% of participants, experienced improvement in two or more outcomes.

Pennesi said this clinical trial shows CRISPR gene editing has exciting potential to treat inherited retinal degeneration.

“There is nothing more rewarding to a physician than hearing a patient describe how their vision has improved after a treatment,” Pennesi continued.

“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. Further study is needed to confirm these results and optimize future treatments,” Pennesi said.

After reviewing this study, David I. Geffen, OD, FAAO, director of optometric and refractive services at the Gordon Schanzlin New Vision in La Jolla, CA, told MNT this is a landmark investigation in treating genetic mutations that impair an individual’s life.

“CRISPR gene editing is the hope to help fix many of (these) degenerations, disorders, and diseases of our time,” Geffen continued. “The ability to use gene therapy to correct a disorder like LCA is a huge breakthrough in medical science.”

Treating disorders like LCA will be the first stage in the ability to treat many of the genetic mutation disorders we see commonly in practice,” he added. “If this treatment proves very successful we may see a potential to stop many other disorders of the eye, as well as systemic issues.”

MNT also spoke with Benjamin Bert, MD, a board certified ophthalmologist at MemorialCare Orange Coast Medical Center in Fountain Valley, CA, about this study.

Bert commented this is a fascinating study because it allows a treatment for a disease that has had very few options.

“Having a treatment that targets the origin of the disease is always preferred and this study demonstrates that it is possible,” he continues. “It is important to have a treatment for LCA, as well as many of the inherited retinal dystrophies since retinal diseases can cause significant visual impairment.”

“The next steps for the research would be to fully investigate the safety. The viral vector that is used to transfer the treatment can create inflammation, which can have serious side effects in the eyes. It appeared in the small group they used for this study that there were no major side effects, but a larger study is needed to fully investigate the safety.”

— Benjamin Bert, MD, opthamologist

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