Aleksandra Rachitskaya, MD, tells Hallie Levine
Being diagnosed with Inherited Retinal Dystrophy (IRD) can be devastating. These rare inherited eye diseases cause progressive vision loss and sometimes blindness. At the Cleveland Clinic, we see more patients with IRD than ever before. Our numbers have grown from 327 patients in 2015 to nearly 800 in 2019. what is the reason? We’ve all gotten better at diagnosis and treatment.
Over the past 2 years, we have learned about 300 genes are associated with IRD. 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 what genetic mutation is causing your disease, we can often refer you to appropriate clinical trials, which may help improve or preserve your vision. Even if we can’t do it now, thanks to gene therapy, there’s a good chance that within the next year or two, there will be a revolutionary new treatment that will save your sight.
Here’s why we’re so excited about gene therapies, what’s available now, and how to find clinical trials near you.
Why gene therapy for IRDs is so promising
In gene therapy, abnormal genes are replaced with normal ones. While there are many ways to do this, the most common way is to use a vector — a virus without a disease-causing part — to deliver healthy genes into cells. This is done by doctors performing surgery on the eye. The hope is that the cells with the new functional copy of the gene will now function normally.
It turns out that 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 accessible compared to other parts of the body, such as the heart or lungs. The second is that the eyes have “immune privilege”. This means its immune response is not as active as the rest of the body. This is important because when you inject a viral vector with the normal gene into the eye, you don’t want the eye to overreact.
What are the current treatments for IRD?
There is only one FDA-approved gene therapy for an inherited retinal disease: Luxturna, which was approved in 2017.It specifically targets people with mutations in the IRD gene RPE65 Gene. This can be seen in two diseases: retinitis pigmentosa and Leber congenital amaurosis (LCA).This treatment provides a functional copy of RPE65 The gene enters the retinal cells of the eye. These cells then produce normal proteins that convert light into electrical signals in the retina. This helps slow the progression of disease and vision loss in patients.
Patients with these forms of IRD first find that they have trouble seeing at night. Then they start to lose peripheral or side vision, and finally their central vision. During Luxturna’s clinical trials, researchers had patients go through a running maze before and after treatment. Nearly all found their ability to navigate the maze significantly improved, even in the darker environments, which are often more difficult. There are some amazing stories of children whose sight has been restored through this procedure.
Numerous other clinical trials are underway at medical centers across the country. At the Cleveland Clinic, we are recruiting patients with a type of retinitis pigmentosa called X-linked retinitis pigmentosa. Since this is an X-linked disorder, it primarily affects males because they have only one copy of the X chromosome that carries the mutation. (In females, the effects of the mutation are masked by a second, healthy copy of the X chromosome. But they can still be carriers of the disease, and sometimes do experience vision changes.) We will use gene therapy to target eligible of the patient’s eye in an attempt to prevent the disease from progressing to more severe stages.
There are other gene therapy clinical trials underway for other IRDs, such as anchoroideremia and achromatopsia. It promises to stop the progression of vision loss and sometimes even improve it.
Why Gene Therapy Offers Hope for IRD Patients
Gene therapy has the potential to revolutionize the treatment of inherited retinal diseases. As recently as a decade ago, patients would visit an ophthalmologist with no choice but to treat low vision. Now, we can test them for the specific gene mutation that causes the disease and, ideally, link them to a gene therapy trial to replace the malfunctioning gene.
It’s important to understand that if you have IRD and it’s already severe, introducing healthy normal genes won’t do much. You want to catch and treat the disease before it gets too far. This is why genetic testing itself is so important. Once that’s done, we can do a nationwide search to see if any clinical trials are available. You can also stay up-to-date on active and recruiting clinical trials in the United States and around the world at https://clinicaltrials.gov.
I think it’s important to keep your eyes healthy, even if you have undiagnosed IRD yourself but have a family history. 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. In this way, the IRD can be collected as early as possible.
Further down the line, cell therapy is exciting. Here, diseased retinal cells are replaced by stem cells that can develop into healthy cells. Research on this is still in a very early stage and the science is not as solid as gene therapy. But this type of treatment may hold promise, not only for patients with IRD, but also for those with other common retinal diseases such as age-related macular degeneration.
Overall, the future has never been brighter for IRD patients. We can’t promise them 20/20 vision, but we can hope to introduce them to clinical trials that will improve their vision.
