By Aleksandra Rachitskaya, MD, as told to Hallie Levine
It can be devastating to be diagnosed with hereditary retinal dystrophy (IRD). These rare, hereditary eye diseases cause progressive vision loss and sometimes even blindness. Here at the Cleveland Clinic, we have seen more patients than ever before with IRDs. Our number has increased from 327 patients in 2015 to almost 800 in 2019. The reason? We have become much better at both diagnosis and treatment.
Over the past two decades we have learned that there are approximately 300 genes associated with IRDs. Thanks to advances in genetic testing technology, we can diagnose gene mutations in more than 70% of all cases.
That’s great news because once we know which genetic mutation is causing your disease, we can often refer you to an appropriate clinical trial that can help improve or preserve your vision. Even if we can’t do that now, thanks to gene therapy there is a very real chance that in the next decade or two there will be a revolutionary new treatment to save your sight.
Here’s why we’re so excited about gene therapy, what’s available now, and how to find a clinical trial near you.
Why gene therapy for IRDs is so promising
Gene therapy involves replacing an abnormal gene with a normal gene. Although there are many ways to do this, the most common way is to use a vector – a virus without the disease-causing parts – to deliver a healthy gene into the cells. This is done through surgery on the eye by a doctor. The hope is that the cells with the new, functional copy of a gene will now work properly.
It turns out that the eye itself is actually an ideal candidate for gene therapy. There are a number of reasons for this. One is that the retina itself is relatively easy to reach compared to other parts of your body, such as your heart or lungs. The second is that the eye is “immune privileged.” This means that the immune response is not as active as in other parts of the body. That’s important because when a virus vector with a normal gene is injected into the eye, you don’t want the eye’s immune response to go into overdrive.
What treatments are currently available for IRDs?
There is only one FDA-approved gene therapy for inherited retinal diseases: Luxturna, which was approved in 2017. It is specific to people with IRD who have mutations in the RPE65 gene. This can be observed in two diseases: retinitis pigmentosa and Leber congenital amaurosis (LCA). The treatment produces a functional copy of the RPE65 gene in the retinal cells of the eye. These cells then produce the normal protein that converts light into an electrical signal in the retina. This helps slow the progression of a patient’s disease and vision loss.
Patients with these forms of IRD primarily notice that they have difficulty seeing at night. They then begin to lose their peripheral or side vision, and eventually their central vision. During Luxturna’s clinical trials, researchers had patients go through a mobility maze both before and after treatment. Nearly all saw significant improvements in their ability to get through the maze, even in darker environments, which tend to be more difficult. There have been some amazing stories of children whose sight has been restored by this procedure.
Many other clinical trials are underway at medical centers across the country. Here at the Cleveland Clinic, we enroll patients with a type of retinitis pigmentosa known as X-linked retinitis pigmentosa. Because this is an (In women, the effect of the mutation is masked by the second healthy copy of the target patients. to prevent the disease from developing into a more serious stage.
Other gene therapy clinical trials are also underway for other IRDs, such as choroideremia and achromatopsia. It holds promise for halting the progression of vision loss and sometimes even improving vision.
Why gene therapy gives hope to people with IRDs
Gene therapy has the potential to revolutionize the treatment of inherited retinal diseases. Just a decade ago, patients visited ophthalmologists and were offered nothing but low vision therapy. Now we can test them for specific genetic mutations that cause disease, and ideally link them to a gene therapy trial to replace that faulty gene.
It is important to understand that if you have an IRD and it is already advanced, introducing a healthy normal gene will not do much. You want to catch and treat the disease before it progresses too far. That’s why genetic testing itself is so important. Once it’s ready, we can search across the country to see if a clinical trial is available. You can also stay informed about active and recruiting clinical trials in the United States or even worldwide at https://clinicaltrials.gov.
I think it’s important to stay on top of your eye health, even if you don’t have a diagnosed IRD yourself but have a family history of one. If recommended by your doctor or genetic counselor, it is important to have genetic testing to ensure you are not a carrier, and to encourage other family members to get tested as well. This way, an IRD can be collected as early as possible.
Looking even further down the pipeline, there is a lot of excitement around cell therapy. Here, diseased retinal cells are replaced by stem cells that can develop into healthy cells. Studies on this are still at a very early stage and the science is not yet as robust as that for gene therapy. But this type of treatment may hold promise not only for people with IRDs, but also for people with other common retinal diseases, such as age-related macular degeneration.
Overall, the future has never looked brighter for people with IRDs. We can’t promise them 20/20 vision, but we can hopefully introduce them to a clinical trial that can improve their vision.