Gene Therapy for Macular Degeneration: Benefits and Procedure

Gene therapy is an emerging treatment for both wet and dry macular degeneration. It requires fewer eye injections than standard treatments.

Macular degeneration, also called age-related macular degeneration (AMD), affects your ability to see things straight ahead of you. This makes it difficult to perform daily activities like reading and driving.

This progressive eye disorder is the most common cause of vision loss in people over age 65 in the United States.

AMD occurs when the macula, a small area in the center of your retina, deteriorates. This leads to central vision loss, but your peripheral vision is usually not affected.

There are two types of AMD:

• Dry macular degeneration: The most common type, dry AMD occurs when the retinal pigmented epithelial and photoreceptor cells on your macula degrade. It develops gradually and may progress to wet AMD.
• Wet macular degeneration: Abnormal blood vessels grow under the retina due to a protein called vascular endothelial growth factor (VEGF). Wet AMD develops and progresses more rapidly than dry macular degeneration.

The treatment for AMD depends on the type. Treatment generally involves antioxidant vitamins for dry AMD and anti-VEGF eye injections for wet AMD.

According to the Académie américaine d'ophtalmologie, anti-VEGF treatment stabilizes vision in 90% of people who receive it and improves vision in about one-third of them.

There’s currently no cure for either dry or wet AMD.

Gene therapy is a new and promising treatment that may target both dry and wet AMD. Although it may not cure AMD, gene therapy could eliminate the need for ongoing eye injections.

How does gene therapy work to treat macular degeneration?

Gene therapy for macular degeneration involves inserting a genetically modified adeno-associated virus (AAV) into your eyes’ retinal cells. AAV blocks VEGF to prevent the growth of abnormal blood vessels.

AAV delivers therapeutic genes that interfere with the activity of retinal cells. The modified retinal cells can then begin producing their own anti-VEGF proteins.

Unlike other AMD treatments that require a series of eye injections, with gene therapy, only one injection may be necessary. This is because the modified retinal cells can continuously produce therapeutic proteins on their own.

How effective is gene therapy in treating macular degeneration?

Although gene therapy is a new treatment currently in clinical trials, it shows promise for treating both dry and wet macular degeneration.

More research is still needed to further determine the effectiveness and safety of gene therapy for AMD.

Gene therapy effectiveness for dry macular degeneration

Gene therapy for dry AMD reduces the overactive proteins in the retinal cells that may lead to holes in your eyes, called membrane attack complex (MAC).

Participants in the following clinical trials experienced a slowing of the progression of the disease, with no adverse side effects:

• HMR59: This clinical trial by Hemera Biosciences inserts a protein that increases the production of the CD59 protein that prevents the formation of MACs.
• GT005: Conducted by Gyroscope Therapeutics, this clinical trial also prevents MACs from forming. It boosts complement factor I (CFI) proteins, which stop your immune system from attacking your retinal cells.

Gene therapy effectiveness for wet macular degeneration

En cours clinical trials are testing the effectiveness of the following gene therapies for wet AMD that block the activity of VEGF:

• Ixo-vec (ADVM-022): You can receive injections of the modified protein ADVM-022 into your retinal cells in a doctor’s office. In a clinical trial, many participants who previously needed monthly injections of other AMD drugs didn’t need another ADVM-022 injection for over 2 years.
• RGX-314: This gene therapy delivers AAV8, a protein similar to ranibizumab (Lucentis), an injectable drug that treats wet AMD. An AAVIATE clinical trial found that it had only mild adverse effects and reduced the number of injections needed by 66.7% after three years.
• 4D-150: This involves injecting both an anti-VEGF protein and RNA interference (RNAi) into retinal cells. The need for follow-up injections was reduced by 96.7% overall, according to a PRISM clinical trial.

Research summary

Research on gene therapy for AMD is still in the early stages, but the findings so far are promising.

In general, studies show the following:

• Gene therapy is well tolerated, with only mild to moderate side effects.
• Fewer injections are needed compared to traditional AMD treatment.
• Gene therapy helps prevent further vision loss.

HEALTHLINE NEWSLETTER

Get our Macular Degeneration Newsletter

Improve your eye health with our macular degeneration newsletter. Receive expert advice on managing your condition, answers to your FAQs, and the latest on condition breakthroughs delivered to your inbox.

What is the procedure for gene therapy for macular degeneration?

In gene therapy, a doctor may inject genetically modified proteins into your retinal cells in one of the following ways:

• Intravitreal injection: An eye care professional uses a needle to inject the proteins into the vitreous cavity, the fluid between your lens and retina. This is usually painless and can take place during an outpatient visit.
• Subretinal injection: This procedure, which requires Opération de l'œil, is becoming popular among researchers because it allows more precise targeting of the outer retina. Doctors inject proteins directly into the subretinal space, located between the photoreceptors and retinal pigment epithelium (RPE) layers.
• Suprachoroidal injection: Doctors inject proteins targeting the outer retina into the suprachoroidal space between the sclera and choroid. This relatively new procedure can take place in a doctor’s office.

What are the risks of gene therapy for macular degeneration?

In gene therapy clinical trials, 87% of participants reported only mild adverse effects.

Most of the following potential risks are related to the surgical procedure rather than the gene therapy itself:

• eye inflammation triggered by an immune response to the genes
• post-operative subconjunctival hemorrhage (bleeding)
• eye irritation or pain
• reduced sharpness of vision

Finding a clinical trial

As of July 2024, seven AMD gene therapy clinical trials are recruiting participants in the United States, including the following:

• UN phase 3 clinical study with 94 locations is evaluating RGX-314 for wet AMD. Participants must be between the ages of 50 and 88 and have had previous anti-VEGF eye injections.
• UN phase 1 and 2 clinical study with eight locations is evaluating SKG0106 for wet AMD. Participants must be age 50 and older and have had previous anti-VEGF eye injections.
• UN phase 1 and 2 clinical study with 26 locations is evaluating 4D-150 for wet AMD and recruiting people 50 years of age and over who’ve been diagnosed with macular choroidal neovascularization (CNV) secondary to AMD.

Frequently asked questions

What is the newest treatment for macular degeneration?

The Food and Drug Administration (FDA) approved the following injectable drugs in 2023 to slow the progression of geographic atrophy, an advanced stage of dry AMD:

• Izervy (avacincaptad pegol): This drug blocks complement C5, a protein that may worsen dry AMD.
• Syfovre (pegcetacoplan): The first FDA-approved drug for dry AMD, it also blocks complement protein C5.

How close are we to a cure for macular degeneration?

Researchers are making rapid and significant progress in developing effective treatments for AMD. Emerging treatments such as gene therapy and stem cell therapy may lead to a cure in the next several years.

Is there a gene for macular degeneration?

Although genetic factors may increase the risk of developing AMD, a single gene does not lead to this disease.

Studies have identified more than 30 genes with possible links to AMD. Variations in the following two genes in particular may put you more at risk for developing AMD:

• complement cascade genes on chromosome 1
• ARMS2/HTRA genes on chromosome 10

Emporter

While gene therapy is a relatively new treatment for macular degeneration, the research conducted to date suggests it effectively reduces the need for ongoing eye injections without adverse effects.

Gene therapy does not, however, cure AMD.

Further research is necessary to improve the effectiveness of gene therapy and to better determine its long-term effects.