By Aleksandra Ratchitskaya, MD, as told to Haley Levine
It can be devastating to be diagnosed with hereditary retinal dystrophy (IRD). Rare, inherited eye diseases cause progressive vision loss, and sometimes even blindness. Here at the Cleveland Clinic, we’ve seen more patients with IRDs than ever before. Our numbers have increased from 327 patients in 2015 to nearly 800 patients in 2019. Why? We are getting much better at diagnosing and treating.
Over the past two decades, we have learned that there are about 300 genes associated with IRDs. Thanks to advances in genetic testing technology, we are able to diagnose genetic mutations in more than 70% of all cases.
This is great news, because once we know what genetic mutation is causing your disease, we can often refer you to an appropriate clinical trial that may help improve or preserve your vision. Even if we can’t now, thanks to gene therapy, there’s a very real chance that, in the next decade or two, there may be a revolutionary new treatment to save your eyesight.
Here’s why we’re so excited about gene therapy, what’s available now, and how to go about finding a clinical trial near you.
Why gene therapy for IRDs is so promising
In gene therapy, the abnormal gene is replaced by a normal one. While 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 an intact gene into cells. This is done through eye surgery by a doctor. The hope is that cells with a new, functional copy of the gene will now function properly.
As it turns out, the eye itself is actually an ideal candidate for gene therapy. There are several reasons for this. One is that the retina itself is relatively easy to access compared to other parts of your body, such as the heart or lungs. The second is that the eye is “immunologically privileged”. This means that his immune response is not as active as it is 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 overdrive.
What treatments are currently available for IRDs?
There is only one FDA-approved gene therapy for inherited retinal disorders: Luxturna, which was approved in 2017. It is intended for people with IRD who have mutations in the retina. RPE65 gene. This can be seen in two diseases: retinitis pigmentosa and Leber congenital disease (LCA). The treatment delivers a functional copy of the RPE65 gene in retinal cells. These cells then produce the normal protein that converts light into an electrical signal in the retina. This helps slow the progression of the patient’s disease and vision loss.
Patients with these forms of IRD first find that they have difficulty seeing at night. Then they start to lose their peripheral or side vision, and eventually their central vision. During clinical trials of Luxturna, researchers had patients go through a kinetic maze before and after treatment. Almost all of them saw significant improvements in their ability to traverse the maze, even in a darker environment, which is usually more difficult. There have been some amazing stories of children having their sight restored through this procedure.
There are many other clinical trials taking place at medical centers across the country. Here at Cleveland Clinic, we enroll patients with a type of retinitis pigmentosa known as X-linked retinitis pigmentosa. Since this is an X-linked disorder, it primarily affects males, as they have one copy of the X chromosome that carries the mutation. (In women, the effect of the mutation is masked by the second healthy copy of the X chromosome. But they can still be carriers of the disease and sometimes have visual changes.) We will use gene therapy to target one eye of eligible patients to 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 achromatopsia. It shows promise for halting the progression of vision loss, and sometimes improving vision, too.
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Gene therapy has the potential to revolutionize the treatment of inherited retinal disorders. Just a decade ago, patients would see ophthalmologists and only be offered treatment for low vision. Now, we can test them for specific disease-causing gene mutations, and ideally link them to a trial of gene therapy to replace that malfunctioning gene.
It is important to understand that if you have an IRD and it is already very advanced, inserting a healthy normal gene will not do much good. You want to catch the disease and treat it before it gets too far. This is why genetic testing itself is so important. Once that’s done, we can search around the country to see if there’s a clinical trial available. You can also stay up to date regarding active clinical trials and recruitment in the US or even globally via https://clinicaltrials.gov.
I think it’s important to stay informed about your eye health even if you don’t have a diagnosis of IRD yourself but do have one family history. If your doctor or genetic counselor recommends it, it’s important to have genetic testing to make sure you’re not pregnant, and to encourage other family members to get tested as well. In this way, the IRD can be captured as soon as possible.
Looking further afield, there is a lot of excitement surrounding cell therapy. This is where diseased retinal cells are replaced with stem cells that can develop into healthy cells. Studies on this are still in very early stages, and the science is not as strong as gene therapy. But this type of treatment may hold promise, not only for people with IRDs, but also for those with other common retinal diseases, such as age-related macular degeneration.
In general, the future has never been brighter for people with IRDs. We can’t promise them 20/20 vision, but we can offer them a clinical trial that may improve their eyesight.