- Retinitis pigmentosa is one of the leading causes of blindness in humans.
- In a recent study, researchers used CRISPR gene editing to restore vision loss in mice with the condition.
- Experts say CRISPR gene editing shows promise for being used to correct vision loss in humans.
Researchers restored sight in mice with retinitis pigmentosa by using gene editing, according to a study published today in the Journal of Experimental Medicine.
The disease is one of the significant causes of blindness in humans. More than 100 locations on 50 genes have been linked to retinitis pigmentosa. In this study, scientists targeted a mutation in the enzyme PDE6βk a protein that’s vital for visual signaling in the retina.
The scientists used the CRISPR system of gene editing, allowing them to correct gene mutations. The researchers said the changes in the genome restored the enzyme’s activity in the retinas of mice and prevented the death of photoreceptors to restore normal electrical responses to light.
After correcting the gene mutation, the researchers performed several behavioral tests to confirm that the mice continued their improved vision into old age.
One such test was to have the mice find their way out of a visually guided water maze. The scientists noted that the mice performed almost as well as healthy mice.
Another test was to observe the head movements of the mice in response to visual stimuli. The mice that received the gene editing again showed behavior typical for a mouse with healthy vision.
“CRISPR-based gene-editing has revolutionized medicine with endless possibilities,” said Dr. Vaidehi Dedania, a retinal surgeon at the NYU Langone Eye Center and associate professor in the Department of Ophthalmology at NYU Grossman School of Medicine in New York.
“This study for retinitis pigmentosa is fascinating and provides insight into what is possible for patients with this degenerative genetic disease,” she told Healthline.
The promise of gene editing
The techniques used by the researchers could go beyond retinitis pigmentosa and could be a frontrunner in treating other genetic diseases.
“This is exciting evidence of the ability to correct blinding retinitis pigmentosa-like disorders in mice with a technique, which, hopefully, will evolve into human clinical trials,” said Dr. Howard R. Krauss, a surgical neuro-ophthalmologist and the director of Pacific Neuroscience Institute’s Eye, Ear & Skull Base Center at Providence Saint John’s Health Center in Callifornia.
“Having unlocked the molecular mysteries of genetic disorders decades ago, we have dreamed of reaching into the cell to add the missing genetic material,” he told Healthline. “There are now about 20 FDA-approved gene therapies for a variety of diseases. Yao and colleagues have made great strides in developing and demonstrating means of treating a wider variety of genetic retinal degenerative disorders.”
The researchers indicated that much work must still be done to establish human safety and efficacy for these types of surgeries.
What is retinitis pigmentosa?
Retinitis pigmentosa is the name given to a group of disorders that produce gradual loss of vision, according to the National Eye Institute.
It affects about 1 in 4,000 people in the United States.
It is typically bilateral. However, there are rare instances where it occurs in only one eye.
“Retinitis pigmentosa can have different levels of expression in different patients,” said Dr, Benjamin Bert, an ophthalmologist at MemorialCare Orange Coast Medical Center in California.
“However, most patients have a gradual loss of their peripheral vision and many have changes to their macules affecting their central vision. With the significant progression of the disease, blindness is unfortunately possible,” he told Healthline.
The first symptom s is usually the loss of night vision. As the disease progresses, it can cause tunnel vision.
In the late stages, people can experience photopsia – perceived flashes of light, loss of accurate color discrimination, and loss of visual acuity.
The condition can also lead to complete vision loss. However, most people maintain some light perception.
People who develop the disease might have experienced visual disturbances, such as not seeing well in low-light situations. Most people experience a narrowing of the visual field over time.
Some might find driving challenging at night because they struggle to transition from the bright light of oncoming headlights to nighttime darkness.
“Until recently, there weren’t any treatments for retinitis pigmentosa. There is currently an FDA-approved therapy for patients with a specific gene mutation resulting in vision loss,” Dedania said. “The therapy, Luxturna, has opened possibilities to patients that would otherwise continue to lose vision. They have had improvements in their vision-guided behavior after the treatment.”
What you need to know about genetic treatments
There are two types of genetic treatments: gene therapy and gene editing.
“Genetic treatment approaches aim to correct the defective genes by either supplying entire normal genes to compensate for the defective ones (gene therapy) or by replacing specific genetic mutations with normal genetic information (gene editing),” said Dr. Aaron Brock Roller, a vitreoretinal surgeon at Austin Retina Associates in Texas.
“Of these approaches, gene therapy is currently at the forefront of medical treatment. Current clinical trials for retinitis pigmentosa utilize gene therapy. These trials are all very promising,” Roller told Healthline. “The only FDA-approved treatment of retinal disease utilizes viral gene therapy to restore useful vision in patients with blindness due to Leber congenital amaurosis, a condition similar to retinitis pigmentosa. Despite the success of gene therapy, significant limitations exist. Gene therapy approaches most used in clinical trials are only theoretically able to treat a specific subset of genetic diseases. Many of the most common and devastating forms of retinitis pigmentosa and other retinal dystrophies remain out of the reach of standard gene therapy techniques.”
Gene editing might offer the most hope to people with retinitis pigmentosa. Both approaches use a gene-delivery system, which has a size limit. Gene therapy cannot handle the number of new genes needed to treat the disease best, Roller explained.
Since gene editing modifies the existing genetic information, a size limit does not apply, greatly expanding the range of treatment options.
“Anything that can be done to help patients with retinitis pigmentosa would be a fantastic advancement in our treatment,” Bert said. “Retinitis pigmentosa causes vision changes and vision loss early in life, making everyday activities, like navigating a room or a hallway, very difficult. Having a treatment to stop the progression of the disease would be wonderful.”
However, there are issues with bringing gene therapy and gene editing to everyday healthcare. A significant problem is the cost.
“Major concerns in the development of gene therapy include expense, with today’s price tag often in the millions of dollars for treatment of one patient,” Krauss said. Searching for techniques to reduce the transmission of genetic disorders is just as important, if not more important. “To prevent rather than treat; whereas an ‘ounce of prevention’ was once worth ‘a pound of cure,’ today it may be worth millions of dollars of cure.”
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