UF Health researchers’ gene therapy for retina disorder shows promise in early testing

Researchers also found their work in mice also established that the therapy can be effective even when retinitis pigmentosa has taken hold. (Adobe Stock image)

For patients diagnosed with retinitis pigmentosa, the way they see the world can start to change early in life, starting with a decline in night and peripheral vision that ultimately leaves them blind.

Researchers at the University of Florida College of Medicine hope to develop a solution: A gene therapy that has now succeeded in three animal models.

According to a University of Florida Health news release, the researchers, working with mice, used gene therapy to both knock down and replace malfunctioning genetic material that affects light-sensing photoreceptors in the retina.

The study was published recently in the journal Vision Research and show the therapy can work in different species, which can help advance these efforts to human clinical trials, Alfred S. Lewin, PhD, a professor emeritus at the University of Florida College of Medicine’s Department of Molecular Genetics and Microbiology. 

The retinas of treated and control animals at nine months showed improved thickness of all layers of the treated retinas and particularly the photoreceptor layers. (Image courtesy of University of Florida College of Medicine)

The UFH news release noted that the therapy works by addressing unique mutations in the gene for rhodopsin, a protein crucial to the eye’s light-sensing system. It should work for the 100-plus rhodopsin mutations known to exist, Lewin said.

“The objective was to confirm that this therapy, which was tested previously in other animals, works in a different species with a different mutation. We also wanted to show that the therapy could have benefit after retinal degeneration has already started,” Lewin said in the university news release.

In both cases, the answer was definitive. Mouse eyes treated with the gene therapy retained half of their retinal thickness — a key measure of preserving photoreceptors — after nine months, the researchers found. The eyes in untreated mice lost 40% of their retinal thickness after just one month and half of their photoreceptors in three months.

Moreover, Lewin noted in the news release that researchers were pleased with the results and it gave them reason to believe the therapy could work long term for humans.

A genetically inherited disorder, retinitis pigmentosa typically strikes humans in the first or second decade of life, and affects one of every 5,000 people worldwide, according to the National Institutes of Health. There is no cure and no approved treatments for retinitis pigmentosa.

“Our ultimate goal would be to treat patients as early as we can — even before vision is lost — and while they can still learn to read and recognize the world around them,” Lewin said in the news release.

During the study, researchers made an discovery, treating one eye with the gene therapy also delivered some beneficial DNA to the animals’ untreated eyes, although at lower levels than the treated eyes. Among mice that received the therapeutic virus, the survival of photoreceptors was improved at all ages and in both eyes.

Chulbul M. Ahmed, PhD, a research assistant professor in the department of molecular genetics and microbiology and a co-author of the paper, pointed out that researchers are encouraged by the bilateral benefit even if the mechanics of how an untreated eye benefits from treatment in a companion eye aren’t yet fully understood.

“You don’t necessarily have to treat both eyes. With treatment in one eye, the counterpart eye appears to get some benefit from that,” Ahmed said in the release.

Researchers also found their work in mice also established that the therapy can be effective even when retinitis pigmentosa has taken hold.

“We wanted to see if we could treat an animal-model patient where degeneration had begun. In fact, we did get benefits in both eyes, even after the disease had already started,” Lewin concluded in the news release.

The researchers will now try to determine the smallest dose that is effective in certain preclinical models, Lewin said. That will help them approximate a dose that is safe for humans, which is another key step before moving into clinical trials.