Hope may be on the horizon for people with retinitis pigmentosa, a rare inherited eye disease with no cure. Existing treatments only help a fraction of the estimated 100,000 Americans with this condition. But advances in gene therapy may soon help restore vision to a greater number of people.
Retinitis pigmentosa causes light-detecting cells in the retina to break down over time, destroying vision. Mutations in more than 60 different genes can contribute to this condition.
“If you are diagnosed with retinitis pigmentosa, it’s vital to undergo genetic testing to identify your underlying mutation," says Ninel Gregori, M.D., an Academy member and a professor of clinical ophthalmology at Bascom Palmer Eye Institute.
That's because people with certain genetic mutations may qualify to participate in a clinical trial of a new treatment before it's widely available.
"Knowing which gene causes your disease and asking your ophthalmologist about options to join a clinical trial may help save your vision,” Gregori says.
Existing treatments for retinitis pigmentosa
Two treatments are currently available for patients with retinitis pigmentosa.
Correcting mutations in the RPE65 gene
The gene therapy Luxturna is only for patients with a mutation in both copies of the RPE65 gene. Because of this mutation, the retina doesn't respond properly to light. A single injection of Luxturna delivers a healthy copy of the RPE65 gene directly to the retina. This restores the retina's ability to respond to light.
If patients receive the treatment early enough after diagnosis, Luxturna can improve night vision and help patients better navigate in low-light conditions.
Luxturna was developed by Spark Therapeutics and approved in 2017 by the U.S. Food and Drug Administration. It costs $850,000 for both eyes, which may be covered by insurance.
Treating advanced retinitis pigmentosa
Patients with advanced retinitis pigmentosa may experience some minor improvements in vision using the Argus II bionic eye. Patients who benefit from this treatment often have very low visual acuity, and may only be able to perceive light. A surgery is required to place a small electronic device on the retina. Patients must also wear a special pair of glasses mounted with a video processing technology. The glasses send images to the device, which stimulates light-sensing cells in the retina and transmits these images to the brain.
Earlier this year, Second Sight Medical Products announced a redesigned set of glasses for use with previously implanted Argus II systems, but the glasses are not yet commercially available. Although new Argus II implants are no longer available, a different implant is in early development in Australia.
Future treatments in development for retinitis pigmentosa
Several new treatments on the horizon aim to benefit people with retinitis pigmentosa. Many of these therapies are still being tested, and it will likely be several years before they become available to patients. But the results so far are promising. Ask your ophthalmologist whether you qualify for a clinical trial.
A new treatment that may benefit all types of retinitis pigmentosa
GenSight Therapeutics is testing a treatment that has the potential to help people with retinitis pigmentosa regardless of their genetic mutation. Treatments that use light as a tool to control cells are known as optogenetic therapies.
The optogenetic therapy from GenSight combines an eye injection with the use of high-tech goggles. The injection delivers a gene that helps retinal cells respond to light. The goggles allow these cells to send electrical signals to the brain. Together, the injection and goggles attempt to replicate the work of light-sensing cells called photoreceptors, which don't work well in people with retinitis pigmentosa.
Patients must train for several months to learn how to use the goggles. So far, five patients have had the treatment. Some have gained the ability to distinguish high-contrast objects on a table and identify crosswalk lines on the street. They are still not able to read, recognize faces or drive. Other companies pursuing optogenetic therapies include Retrosense Therapeutics (Allergan), Nanoscope Therapeutics, and Vedere Bio, Inc. (Novartis).
Gene therapies for X-linked retinitis pigmentosa
People with an aggressive form called X-linked retinitis pigmentosa may benefit from experimental gene therapies in development by three companies: Meira GTX, Applied Genetic Technologies and BioGen. This condition is caused by a mutation in the RPGR gene and typically affects men.
All three treatments involve a procedure called vitrectomy and an eye injection that delivers healthy copies of the RPGR gene to a part of the retina called the macula. Some patients in the clinical trials who received treatment in one eye experienced improvements in their field of vision, light sensitivity and ability to navigate in a dark room. A company called 4D Molecular Therapeutics is testing another type of gene therapy that does not require a vitrectomy.
Correcting errors in the USH2A gene
ProQR Therapeutics is developing a gene therapy that could stop vision loss in people with retinitis pigmentosa and Usher syndrome caused by a mutation in the USH2A gene. This mutation prevents patients from making the USH2A protein, which is essential for vision. The therapy, called QR-421a, is injected into the retina and allows cells to produce a healthier version of the USH2A protein. So far, patients with both advanced and early-moderate disease experienced improvements in both visual acuity and field of vision. ProQR Therapeutics expects to test the therapy in a phase 2-3 clinical trial in the fall of 2021.
Correcting errors in the RHO gene
Another study by ProQR Therapeutics is testing a treatment for people who have retinitis pigmentosa due to a mutation in the RHO gene. This is also known as RP4. This mutation causes patients to produce a faulty version of the rhodopsin protein, which normally converts light into an electrical signal. The faulty protein becomes toxic to the retina over time. The new treatment, QR-1123, is delivered by an eye injection and prevents the faulty protein from being made. This allows the normal version of the protein to rule the retina again. This therapy is currently being studied in a phase 1-2 clinical trial.
Treating Leber congenital amaurosis, type 10
Leber congenital amaurosis is a form of retinitis pigmentosa that affects infants. This disease destroys light-sensing cells in the retina. Type 10 disease is caused by a defect in the CEP290 gene that leads to progressive vision loss and, in many cases, legal blindness.
There are two promising treatments in development for this treatment.
Scientists have developed a gene-editing tool called CRISPR to try to remove the genetic defect. The treatment is delivered to the retina during an eye injection. Researchers hope the tool will help the retina produce a protein that keeps cells from dying and also revives some dead cells. This could help patients regain some vision. Allergan and Editas Medicine are leading the phase 1-2 BRILLIANCE clinical trial with 18 patients to test this treatment.
ProQR Therapeutics is testing a type of gene therapy known as RNA antisense oligonucleotide therapy. This treatment is delivered via an eye injection, and it allows production of a protein needed for vision. Patients in an ongoing phase 2-3 clinical trial are experiencing significant improvements in vision and retinal structure several months after injection.
These treatments could help patients avoid debilitating vision loss due to retinitis pigmentosa.
“Gene therapy for some forms of retinitis pigmentosa offer the potential of halting the otherwise relentless progressive loss of vision and visual field. In some patients, it may actually improve vision, light sensitivity, and ability to see and navigate in the dark, ” says Christine Kay, MD, director of retinal genetics at Vitreoretinal Associates in Gainesville, FL.