In a small and preliminary clinical trial, Johns Hopkins researchers and their collaborators have shown that an experimental gene therapy that uses viruses to introduce a therapeutic gene into the eye is safe and that it may be effective in preserving the vision of people with wet age–related macular degeneration (AMD).

The study published on May 16 in The Lancet journal, reports an exciting new approach in which a virus, similar to the common cold, but altered in the lab so that it is unable to cause disease, is used as a carrier for a gene and is injected into the eye. The virus penetrates retinal cells and deposits a gene, which turns the cells into factories for productions of a therapeutic protein, called sFLT01.

Eye specialists say the burden and discomfort of the regimen is responsible for many patients not getting injections as frequently as they need, causing vision loss.

The investigators designed their virus to target retinal cells and provide them with a gene that produces sFLT01. Thus, retinal cells become factories that produce the therapeutic protein — potentially eliminating the need to repeatedly inject it.

The phase 1 clinical trial involved 19 men and women, 50 years old or older with advanced wet AMD.

Participants were divided into five different groups that received increasing doses from 2X10^8 to 2X10^10 viral particles containing the therapeutic gene in 0.05 mL of fluid. Each group was examined by investigators for signs of adverse reactions for at least 4 weeks before administering a higher dose to the next group.

After the virus deposited the gene, the cells began secreting sFLT01 which bound to VEGF and prevented it from stimulating leakage and growth of abnormal blood vessels. The goal is for the retinal cells infected by the virus to produce enough sFLT01 to permanently stop the progression of AMD.

“Even at the highest dose, the treatment was quite safe. We found there were almost no adverse reactions in our patients,” Campochiaro says.

For safety and ethical reasons, the study group was composed of people for whom standard approved treatments were highly unlikely to regain vision, meaning in part that only 11 of the 19 had the potential for fluid reduction. Of those eleven patients, four showed dramatic improvements. The amount of fluid in their eyes dropped from severe to almost nothing, just like what is observed with optimal standard treatment, Campochiaro says. In addition, two other participants showed a partial reduction in the amount of fluid in their eyes.

Five participants showed no reduction in fluid levels. Surprisingly, the researchers say, they found that all of the patients who did not show improvement had pre–existing antibodies to the AAV2 virus.

From that result, the researchers conclude that even if further studies affirm the safety and value of their gene therapy, it may have limitations for broad use. That’s because an estimated sixty percent of the U.S. population has been infection with adeno–associated virus, the family of viruses that AAV2 belongs to, and have built an immunity to it. The researchers believe that in these patients, the immune system destroyed the virus before it could insert the therapeutic gene. Campochiaro explains, “The numbers are small and simply show a correlation, so we don’t know if serum antibodies are definitely an impediment, but more work is needed to determine this.”