Gene and cell therapies used in treatment

By Aleksandra Rachitskaya, MD, told to Hallie Levine

It can be devastating to be diagnosed with hereditary retinal dystrophy (IRD). These rare, inherited eye diseases cause progressive vision loss and sometimes even blindness. Here at the Cleveland Clinic, we have seen more patients with IRDs than ever before. Our number has gone from 327 patients in 2015 to nearly 800 in 2019. The reason? We have become much better at diagnosis and treatment.

Over the past 2 decades, we have learned that there are approximately 300 genes associated with IRDs. Thanks to advances in genetic testing technology, we are able to diagnose genetic mutations in more than 70% of cases.

This is great news because once we know which genetic mutation is causing your condition, we can often refer you to an appropriate clinical trial that can help improve or maintain your vision. Even if we can’t do it now, thanks to gene therapy, there’s a good chance that within the next ten or twenty years there will be a breakthrough 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

In gene therapy, an abnormal gene is replaced by a normal gene. Although there are many ways to do this, the most common method is to use a vector – a virus without the pathogenic parts – to deliver a healthy gene into cells. This is done through surgery to the eye by a doctor. The hope is that cells with the new functional copy of a gene will now function properly.

It turns out that the eye itself is actually an ideal candidate for gene therapy. There are several reasons for this. The first 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 an “immune privileged”. This means that its immune response is not as active as in other parts of the body. This is important because when a viral 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 IRD?

There is only one FDA-approved gene therapy for inherited retinal disorders: Luxturna, which was approved in 2017. It is specifically for people with IRD who have mutations in the RPE65 embarrassed. This can be seen in two diseases: retinitis pigmentosa and Leber congenital amaurosis (ACL). The processing delivers a working 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 first find that they have trouble seeing at night. They then begin to lose their peripheral, or side, vision, and finally, their central vision. During clinical trials of Luxturna, researchers walked patients through a mobility maze before and after treatment. Almost all saw significant improvements in their ability to navigate the maze, even in a darker environment, which is generally more difficult. There have been amazing stories of children whose vision 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. As it is an X-linked disease, it mainly affects males, as they have only one copy of the X chromosome carrying the mutation. (In females, the effect of the mutation is masked by the healthy second copy of the X chromosome. But they can still carry the disease and sometimes have visual changes.) We will use gene therapy to target one eye of patients eligible try to prevent the disease from progressing to more serious stages.

There are also other gene therapy clinical trials underway for other IRDs, such as choroideremia and color blindness. It shows promise for stopping the progression of vision loss and sometimes even improving vision.

Why gene therapy gives hope to people with DRI

Gene therapy has the potential to revolutionize the treatment of inherited retinal disorders. As recently as a decade ago, patients were seeing ophthalmologists and only being offered therapy for low vision. Now we can test them for specific genetic mutations that cause the disease, and ideally connect them to a gene therapy trial to replace that faulty gene.

It’s important to understand that if you have IRD and it’s already very advanced, introducing a healthy normal gene won’t do much. You want to catch and treat the disease before it progresses too far. This is why genetic testing itself is so important. Once that’s done, we can search across the country to see if there’s a clinical trial available. You can also keep up to date with ongoing and recruiting clinical trials in the United States or even around the world via

I think it’s important to stay on top of your eye health even if you don’t have IRD diagnosed yourself but have a family history of it. If recommended by your doctor or genetic counselor, it is important to have genetic testing to make sure you are not a carrier and to encourage other family members to get tested as well. This way, an IRD can be retrieved as soon as possible.

Looking even further down the pipeline, there is a lot of excitement around cell therapy. This is where diseased retinal cells are replaced by stem cells that can develop into healthy cells. Studies on this are still in their infancy and the science is not as strong as for gene therapy. But this type of treatment may hold promise, not just for people with DRI, but also for those with other common retinal diseases, such as age-related macular degeneration.

Overall, the future has never looked brighter for people with DRI. We can’t promise them 20/20 vision, but we can hopefully introduce them to a clinical trial that might improve their sight.

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