A new treatment option for both wet and dry macular degeneration is gene therapy. Compared to conventional therapy, fewer ocular injections are needed.
Your vision in front of you is affected by macular degeneration, also known as age-related macular degeneration (AMD). Driving and reading are two everyday tasks that become challenging as a result.
The most frequent cause of vision loss in Americans over 65 is this degenerative eye condition.
The macula, a little region in the middle of your retina, deteriorates and causes AMD. Your peripheral vision is typically unaffected, but your core vision is lost as a result.
Two varieties of AMD exist:
- Dry macular degeneration: The most common type, dry AMD occurs when the retinal pigmented epithelium and photoreceptor cells of your macula degenerate. It develops gradually and may proceed to wet AMD.
- Wet macular degeneration: Abnormal blood vessels form under the retina due to a protein called vascular endothelial growth factor (VEGF). Wet AMD develops and progresses more rapidly than dry macular degeneration.
Depending on the type, AMD has different treatments. When treating dry AMD, antioxidant vitamins are typically used, and when treating wet AMD, anti-VEGF eye injections are used.
According to the American Academy of Ophthalmology, anti-VEGF medication stabilizes vision in 90% of persons who receive it and improves eyesight in around one-third of them.
There’s presently no cure for either dry or wet AMD.
A novel and exciting treatment that may address both dry and wet AMD is gene therapy. Gene therapy may be able to replace the requirement for regular eye injections, even if it might not be able to cure AMD.
How does gene therapy work to treat macular degeneration?
A genetically altered adeno-associated virus (AAV) is inserted into the retinal cells of your eyes as part of a gene therapy procedure for macular degeneration. To stop the formation of aberrant blood vessels, AAV inhibits VEGF.
Therapeutic genes that disrupt retinal cell function are delivered by AAV. After that, the altered retinal cells can start generating anti-VEGF proteins on their own.
Gene therapy may only require one injection, unlike conventional AMD treatments that call for many eye injections. This is so that the therapeutic proteins can be constantly produced by the altered retinal cells on their own.
How effective is gene therapy in treating macular degeneration?
Gene therapy has shown promise in treating both dry and wet macular degeneration, despite being a novel treatment now undergoing clinical studies.
Further investigation is required to ascertain the safety and efficacy of gene therapy for AMD.
Effectiveness of gene therapy in treating dry macular degeneration
Gene therapy for dry AMD lowers the membrane attack complex (MAC), or overactive proteins in the retinal cells that can cause holes in your eyes.
The disease’s course was slowed for participants in the following clinical trials, and there were no negative side effects:
- HMR59: A protein that boosts the synthesis of the CD59 protein, which inhibits the creation of MACs, is inserted in this Hemera Biosciences clinical trial.
- GT005: This therapeutic trial, run by Gyroscope Therapeutics, likewise stops MAC formation. It increases the levels of complement factor I (CFI) proteins, which prevent the immune system from destroying the cells in your retina.
Effectiveness of gene therapy for wet macular degeneration
Current clinical trials are investigating the efficacy of the following gene treatments that impede VEGF activity in treating wet AMD:
- Ixo-vec (ADVM-022): In a doctor’s office, you can have injections of the modified protein ADVM-022 into your retinal cells. Many patients who had previously required monthly injections of different AMD medications were able to stop using ADVM-022 injections for more than two years in a clinical trial.
- RGX-314: AAV8, a protein that resembles ranibizumab (Lucentis), an injectable medication used to treat wet AMD, is delivered by gene therapy. According to a three-year AAVIATE clinical trial, there were very minor side effects and 66.7% fewer injections required.
- 4D-150: To do this, retinal cells are injected with RNA interference (RNAi) and an anti-VEGF protein. An overall 96.7% reduction in the requirement for follow-up injections was found in a clinical experiment called PRIM.
Research summary
Although gene therapy research for AMD is still in its infancy, the results are encouraging.
Studies generally indicate the following:
- With just mild to moderate adverse effects, gene therapy is well tolerated.
- In comparison to conventional AMD treatment, fewer injections are
- required.Gene therapy aids in stopping future vision loss.
What is the procedure for gene therapy for macular degeneration?
One of the following methods may be used by a physician to introduce genetically altered proteins into your retinal cells during gene therapy:
- Intravitreal injection: The proteins are injected into the vitreous cavity—the fluid that lies between your lens and retina—by an eye care specialist using a needle. This can happen during an outpatient visit and is typically harmless.
- Subretinal injection: Researchers are starting to favor this surgery-related approach because it makes it possible to target the outer retina more precisely. Proteins are directly injected by physicians into the subretinal region, which is situated between the layers of retinal pigment epithelium (RPE) and photoreceptors.
- Suprachoroidal injection: Targeting the outer retina, doctors inject proteins into the suprachoroidal area between the choroid and sclera. In a physician’s office, this relatively new technique can be performed.
What are the risks of gene therapy for macular degeneration?
87% of patients in gene therapy clinical studies had only minimal side effects.
The majority of the potential hazards listed below are more closely linked to the surgical process than to the gene therapy itself:
- inflammation of the eyes brought on by an immunological reaction to the genes
- bleeding from subconjunctival hemorrhage following surgery
- eye irritation or pain
- reduced sharpness of vision
Finding a clinical trial
Seven AMD gene therapy clinical trials, including the following, are accepting participants as of July 2024 in the US:
- RGX-314 is being tested for wet AMD in 94 locations as part of phase 3 clinical research. Participants must have received prior anti-VEGF eye injections and be between the ages of 50 and 88.
- SKG0106 is being tested for wet AMD in eight locations as part of phase 1 and 2 clinical research. Participants must have received prior anti-VEGF eye injections and be 50 years of age or older.
- Macular choroidal neovascularization (CNV) owing to AMD patients 50 years of age and above are being recruited for a phase 1 and 2 clinical study that has 26 locations and is assessing 4D-150 for wet AMD.
Takeaway
Despite being a relatively new treatment for macular degeneration, research to date indicates that gene therapy can efficiently and safely minimize the need for regular eye injections.
However, AMD cannot be cured by gene therapy.
To increase the efficacy of gene therapy and better understand its long-term implications, more study is required.
FAQs
Is there gene therapy for macular degeneration?
As of right now, there are no effective treatments for dry AMD; however, we have created a novel gene therapy technology that we hope can assist in reducing or even reversing the degeneration.
What is the new treatment for macular degeneration in 2024?
Vabysmo (Faricimab) One of the more recent anti-VEGF drugs authorized by the FDA to treat wet AMD is called Vabysmo (faricimab). It functions by inhibiting the production of aberrant blood vessels and the flow of fluid into the retina, VEGF, and angiopoietin-2 (Ang-2).
Can gene therapy restore vision?
Patients with genetic blindness can partially recover their vision with experimental gene therapy. The CRISPR-based medication is examined by Dr. Jason Comander, director of Mass Eye and Ear’s Inherited Retinal Disorders Service.