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Gene and Cell Therapies Used in Treatment

By Aleksandra Rachitskaya, MD, as told to Hallie Levine

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

Over the last 2 decades, we’ve learned that there are around 300 genes associated with IRDs. Thanks to advances in genetic testing technology, we’re able to diagnose the gene mutations in over 70% of all cases.

That’s great news, because once we know what genetic mutation is driving your disease, we can often refer you to an appropriate clinical trial that may help improve or maintain 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 sight.

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, an abnormal gene is replaced with a normal one. While there are many ways to do it, 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 to the eye by a physician. The hope is that the cells with the new, functional copy of a gene will now work properly.

As it turns out, the eye itself is actually an ideal candidate for gene therapy. There are a couple of reasons for this. One is that the retina itself is relatively easy to reach compared to other parts of your body, like your heart, or lungs. The second is that the eye is “immune privileged.” This means its immune response isn’t 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’s 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 gene. This may be seen in two diseases: retinitis pigmentosa and Leber congenital amaurosis (LCA). The treatment delivers a functional copy of the RPE65 gene into the retinal cells of the eye. These cells then produce the normal protein that converts light to an electrical signal in the retina. This helps to slow down the progression of a patient’s disease and vision loss.

Patients with these forms of IRD first find they have trouble seeing at night. They then begin to lose their peripheral, or side, vision, then finally, their central vision. During Luxturna’s clinical trials, researchers had patients go through a mobility maze both before and after treatment. Almost all of them saw significant improvements in their ability to get through the maze, even in a darker environment, which is usually more difficult. There have been some amazing stories of children whose vision has been restored by this procedure.

There are many other clinical trials going on at medical centers across the country. Here at the Cleveland Clinic, we are enrolling patients with a type of retinitis pigmentosa known as X-linked retinitis pigmentosa. Since this is an X-linked disorder, it mainly affects males, as they have a single 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 do 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 severe stages.

There are also other gene therapy clinical trials going on for other IRDs, such as choroideremia and achromatopsia. It shows promise to halt progression of vision loss, and sometimes even improve vision too.

Why Gene Therapy Gives Hope to People With IRDs

Gene therapy has the potential to revolutionize the treatment of inherited retinal disorders. Just a decade ago, patients would see eye doctors and be offered nothing else but low-vision therapy. Now, we can test them for specific genetic mutations that cause disease, and ideally connect them with a gene therapy trial to replace that malfunctioning gene.

It’s important to understand that if you have an IRD and it’s already very far 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 done, we can search across the country to see if there’s a clinical trial available. You can also stay up to date yourself regarding active and recruiting clinical trials in the United States or even globally via

I think it’s important to stay on top of your eye health even if you yourself don’t have a diagnosed IRD but have a family history of one. If recommended by your physician or genetic counselor, it’s important to get genetic testing to make sure you aren’t a carrier, and to encourage other family members to get tested as well. That way, an IRD can be picked up as early as possible.

Looking even further down the pipeline, there’s a lot of excitement surrounding cell therapy. This is where diseased retinal cells are replaced with stem cells that can develop into healthy ones. Studies on this are still in very early stages, and the science isn’t as robust as for gene therapy. But this type of treatment may hold promise, not just for people with IRDs, but for those with other common diseases of the retina, like 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 may improve their sight.

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