Inherited Retinal Diseases

Inherited retinal disorders—or IRDs—are diseases that can cause severe vision loss or even blindness. Each one is caused by a gene that is not working properly, which creates an opportunity for gene therapy to help slow or stop disease progression.


Inherited retinal disorders affect individuals of all ages, with different types progressing at different rates. However, many are degenerative, which means that they keep getting worse over time. Common types of IRDs include Leber Congenital Amaurosis (LCA), Retinitis Pigmentosa, Choroideremia, Stargardt’s Disease, and Achromatopsia. The goal of gene therapy is to correct or compensate for the faulty gene. IRDs are especially strong candidates for gene therapy treatments, due to the retina’s unique physical makeup. Compared to other organs of the body, the eye is small and easy to access for treatment administration.

Another reason that the eye is an ideal location for gene therapy is that it is considered “immune privileged”. Usually when a foreign substance—like a virus—is detected in our bodies, our immune system works hard to take care of the problem. However, certain areas of the body are immune privileged, which means that our normal immune response isn’t as active. This is typically in areas of our bodies that are very important, and may become damaged if swelling or inflammation occurs. This means that anything that is implanted into the eye—a cell with a corrected gene, for instance—is less likely to be rejected.

Treatment Pipeline

Luxturna for RPE65 Mutation

Developed by Spark Therapeutics and the Children’s Hospital of Philadelphia, Luxturna is the first approved gene therapy for an inherited retinal disorder in the U.S. and is also approved for use in Europe Union. Luxturna delivers a functional copy of the RPE65 gene into the eye.

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Choroideremia: NSR-REP1

Nightstar Therapeutics, a clinical stage gene therapy company, is developing a gene therapy for the treatment of Choroideremia. Currently in phase III of clinical trials, the FDA granted a Regenerative Medicine Advanced Therapy (RMAT) designation to the treatment, which is an FDA program that is intended to speed up the development of regenerative medicines, including gene therapies.

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X-Linked Retinitis Pigmentosa: NSR-RPGR

Nightstar Therapeutics is also working on a gene therapy to help patients with X-Linked Retinitis Pigmentosa. Currently in phase I/II of the clinical trial process, five of 18 patients have shown vision improvements after administration of the gene therapy. This has created a cause for optimism as the treatment continues to be tested for safety and effectiveness.

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X-Linked Retinitis Pigmentosa: RPGR gene

Applied Genetic Technologies Corporation (AGTC) is developing a gene therapy treatment for X-Linked Retinitis Pigmentosa. The treatment is currently in phase I/II of the clinical trial process, and is designed to correct specific mutations to the RPGR gene that cause vision loss in patients.

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Achromatopsia: CNGB3 gene

AGTC is also working on a gene therapy treatment for Achromatopsia, a disease that causes patients to have light sensitivity and loss of color discrimination amongst other symptoms. The treatment, which addresses a mutation in the CNGB3 gene, is currently in phase I/II of the clinical trial process.

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Leber Hereditary Optic Neuropathy (LHON): GS010

Gensight Biologics is working on a gene therapy treatment to help counteract the effects of LHON. The treatment is in phase III of the clinical trial process, and has seen positive results including clinically meaningful improvement in the vision of trial subjects.

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Leber Congenital Amaurosis 10 (LCA10): CRISPR/Cas9

Editas Medicine, a discovery-phase pharmaceutical company, received clinical trial approval from the FDA for their CRISPR/Cas9 gene editing treatment for Leber Congenital Amaurosis. Gene editing is a type of gene therapy that uses systems that are highly precise to directly alter the faulty gene in cells.

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Stargardt Disease: ABCA4 gene

Oxford BioMedica, a gene therapy company located in the U.K., is developing a gene therapy treatment for patients with Stargardt disease. Currently in clinical trial phase I/II, the treatment uses a proprietary technology to deliver the corrective ABCA4 gene to the retina.

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Achromatopsia: CNGB3 Gene

MeiraGTx is also developing AAV-CNGB3, an investigational gene therapy that is in Phase I/II clinical trial. The treatment is designed to deliver a functional copy of the CNGB3 gene in order to restore cone function. AAV-CNGB3 is delivered to the cone receptors at the back of the eye via subretinal injection.

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RPE65 Mutation

MeiraGTx is developing AAV-RPE65, an investigational gene therapy that is being studied in Phase I/II clinical trial. AAV-RPE65 is optimized to deliver the RPE65 to the back of the eye. It is delivered via subretinal injection to the central part of the fovea to cover the largest possible area of viable retina.

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X-Linked Retinitis Pigmentosa: RPGR Gene

MeiraGTx is also developing AAV-RPGR, a gene therapy designed to treat the most common form of XLRP caused by mutations in the RPGR gene.  It is currently being studied in a Phase I/II clinical trial. The extension portion of the Phase I/II trial is currently recruiting adult and pediatric patients in the U.S. and the U.K.

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Preclinical

There are a variety of preclinical studies underway for other treatments designed to help treat IRDs. Preclinical studies are needed before a clinical trial can begin. This stage uses animals to find out if a treatment is safe and likely to be successful.

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From Diagnosis to Treatment

Diagnosis

First, the disease needs to be detected. Depending on the kind of disease, an IRD can show up at different times of a person’s life. It is good practice to see an eye doctor on a regular basis, who can help detect early signs of a serious retinal disease. IRDs can cause irreversible damage, so knowing the diagnosis as early as possible is best. Parents can consider genetic testing before or during pregnancy to determine if the child is at risk of inheriting a disease.

Eligibility

You may be curious how patients can participate in current clinical trials to receive an investigational treatment at no cost, while also benefiting the medical community and others who have the disease. It’s important to keep in mind that IRDs are caused by different gene mutations, and therefore have varied eligibility. Genetic testing is necessary to identify a person’s specific mutation, since more than 260 retinal disease genes have been characterized. If you think you or your child may be eligible for a clinical trial, it’s best to first speak with your primary care physician or ophthalmologist to learn more and determine if it is right for you. Then, the individual must meet the eligibility criteria, which can be based on having a specific gene mutation, the age at the time of dosing and medical history.

Goal of Treatment

It is important to note that gene therapy is not a cure for the disease, but instead a means to control disease progression. By targeting the exact cause of the disease—a faulty gene—gene therapy eliminates the need for recurring interventions. The treatment aims to only need a one-time administration, compared to some treatments for retinal disease where the patients will need direct injections as frequent as every three months.

There’s a variety of ways that gene therapy treatments can be administered to the eye. Most gene therapy approaches use a vector to deliver corrected genetic material into the cell. The most promising vectors are based on viruses—but don’t worry, any disease-causing viral materials have been removed. Vectors can be delivered a variety of ways, including an injection. There are two types of injections into the eye. Intravitreal injections are performed by directly injecting the therapy into the vitreous, a jelly-like fluid near the retina. Subretinal injections are administered into the subretinal space, allowing the therapy to be closer to the target area of the eye to correct the disease.

Access

You may be curious of how patients can participate in clinical trials, or receive an approved treatment like Luxturna. It’s best to speak with your primary care physician or ophthalmologist to learn more and determine if gene therapy is the right option. They can help you find a specialist to administer the treatment or help you find a relevant clinical trial. As mentioned earlier, the individual must meet the eligibility criteria.

Get Involved

At this time, we do not know if or when these gene therapy treatments will be approved by the FDA and commercially available. The overall process can take several years until it is developed to the point of being safe and effective. In the meantime, you can help by becoming involved with patient advocacy organizations. They work hard to raise awareness, fund research, advocate and deliver important news about advances in the field. Many patients suffering from IRDs are unaware that treatment options are in development, and many may even be misdiagnosed. Patient advocacy organizations are a great way to connect with other families and patients affected by IRDs, in case you’re looking for support and advice. The disease may be rare, but you are never alone.

Foundation Fighting Blindness

Choroideremia Research Foundation

Sofia Sees Hope

Curing Retinal Blindness Foundation

Retina International

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