Gene therapy for macular degeneration: What to know

Ocular gene therapy uses a genetically modified strain of an adeno-associated virus (AAV) as its carrier. This virus “infects” the cells and inserts a “code” that alters the retinal cells’ activity.

Treatment aims to slow down macular degeneration, which can cause symptoms such as:

• blurry vision
• straight lines appearing wavy
• a blind spot or dark area at the center of a person’s field of vision

AAV is a relatively safe virus approved by the Food and Drug Administration (FDA) for use in ocular gene therapy.

Macular degeneration occurs as aging damages the macula, a small light-sensitive portion at the center of the retina responsible for processing detailed, clear vision. The condition typically does not cause total blindness but may cause severe vision problems.

There are two types of macular degeneration: dry and wet.

The dry type affects 7–9 in 10 people with macular degeneration. People with dry macular degeneration may have tiny clumps of yellow deposits called drusen, causing gradual vision loss.

Wet macular degeneration, also called “advanced neovascular macular degeneration,” is less common but more severe. It affects 10–15% of people with macular degeneration. It occurs when abnormal blood vessels behind the retina grow under the macula, causing blood and fluid leakage. These cause scarring and rapid macular damage, leading to loss of central vision.

Learn more about the differences between wet and dry macular degeneration.

In dry macular degeneration, there is an imbalance in the complement system — a system of proteins in the immune system that fights bacteria and other pathogens. These proteins become overactive and attack the retinal cells, causing membrane attack complex (MAC) or holes in the eye.

HMR59 clinical trial

There is a clinical trial underway, conducted by Hemera Biosciences, for a therapy called AAVCAGsCD59 (HMR59) for dry and wet macular degeneration. For the procedure, researchers administer an injection of the product into the vitreous cavity of the eye in an office setting.

A protein found on the cell surface called CD59 prevents and blocks MACs from forming. This gene therapy permanently alters the retinal cells to increase their expression of CD59. Phase 1 of the therapy has shown efficacy by slowing the rate of progression without producing adverse reactions.

GT005 clinical trial

Another clinical trial, called GT005 by Gyroscope Therapeutics, also targets MACs. Experts found that complement factor I (CFI) — proteins that prevent the immune system from attacking retinal cells — are low or not functioning in people with dry macular degeneration.

Gene therapy delivers a copy of genes that correctly encode this protein and increase its production. This helps counteract the inflammation caused by the complement system and prevents the body from attacking its retinal cells. This therapy is intended to slow the progression of geographic atrophy, which is an advanced form of dry macular degeneration.

A 2020 study found that GT005 is safe and well-tolerated in mice, leading to a long-term secretion of human CFI in the animals.

Gyroscope Therapeutics also announced positive results from their ongoing Phase 1/2 clinical trial, stating that people tolerated the therapy well and demonstrated increased CFI levels compared with the patients’ baselines.

In the wet type, the virus “infects” retinal cells to produce drugs that block VEGF activity, a protein important for the growth of new blood vessels in the eye.

There are two clinical trials for wet macular degeneration: Eylea (ADVM-022), conducted by Adverum Biotechnologies, and RGX-314, conducted by Regenxbio Inc.

ADVM-022 is in phase 1 trial, while RGX-314 is in phase 1/2. Both are showing high levels of efficacy. There was a reduction in the frequency of annual injections following ADVM-022 injections.

Treatment for AMD depends on its stage and type.

Doctors recommend the following nutritional supplements and lifestyle and dietary changes to help delay the progression of dry macular degeneration:

• having a balanced diet that includes:
  • yellow fruits and vegetables
  • green leafy vegetables
  • fish
• maintaining healthy cholesterol and blood pressure levels
• quitting smoking
• getting regular exercise
• taking vitamin C, vitamin E, copper, zinc, lutein, zeaxanthin, and beta-carotene supplements

Learn about the best vitamins for eye health.

Other treatments for dry macular degeneration are in clinical trials but are not yet available for patients. These include lutein supplementation and patient-derived stem cell therapy.

The potential role of gene therapy is strong based on the promising results of recent and ongoing clinical trials. Aside from this, many preclinical studies also show significant results for treatment options.

However, there are still challenges, particularly in delivering the code to the cells. Most research uses AAV vectors, which can vary in their ability to introduce foreign DNA to the retinal cell depending on injection location. Experts are continually exploring new methods of delivering the vector to the back of the eye.

Macular degeneration is a progressive eye condition. While it currently does not have a cure, a person may take measures to prevent its progression, including eating a balanced diet, taking supplements, and exercising daily.

The field of gene therapy for macular degeneration is rapidly evolving and progressing. If successful, gene therapy can help delay or stop the progression of the disease without the heavy burden of treatment.

People wishing to enroll in one of the clinical trials may ask their doctor or get in touch with clinical trials actively recruiting.