Researchers from the US have found a gene therapy for retinitis pigmentosa that has now succeeded in three animal models.
The findings are significant because they show that the therapy works in different species, which is crucial to advancing it to human clinical trials, said Professor Alfred Lewin from the University of Florida (UF).
For people with retinitis pigmentosa, the world they see often starts changing in childhood or as young adults. Their night and peripheral vision declines, eventually leaving most blind.
In a news release, UF explained that working in mice, the researchers used gene therapy to both knock down and replace malfunctioning genetic material that affects light-sensing photoreceptors in the retina.
The technique deploys a harmless, engineered virus to deliver a functional copy of the gene to the eyes. The therapy led to improved retinal structure and function throughout the nine-month experiment, the news release said.
“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,” Professor Lewin said.
The findings were published recently in the journal Vision Research.1
“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,” Prof Lewin said.
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.
That, Prof Lewin said, gives researchers reason to believe the therapy could work long term for humans.
“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 recognise the world around them,” Prof 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
The researchers also unexpectedly discovered that treating one eye with the gene therapy also delivered some beneficial DNA to the animals’ untreated eyes, although at lower levels.
Among mice that received the therapeutic virus, the survival of photoreceptors was improved at all ages and in both eyes. The researchers said they were encouraged by the bilateral benefit even if the mechanics weren’t yet fully understood.
The 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,” Prof Lewin said.
- Ahmed C.M., Massengill M.T., Ildefonso C.J., et al., Binocular benefit following monocular subretinal AAV injection in a mouse model of autosomal dominant retinitis pigmentosa (adRP). Vision Res. 2023 Feb 9;206:108189. doi: 10.1016/j.visres.2023.108189. Epub ahead of print. PMID: 36773475.