Gene therapy hope for retinitis pigmentosa

Researchers show gene therapy preserved photoreceptors in animals whose retinas were modified to produce a human nerve cell protein

17 Jul 2015 by Ryan O'Hare

Tweaking photoreceptors to produce a nerve growth protein could open up new avenues of treatment for patients with retinitis pigmentosa, according to new research.

The findings come from a study by an international team of scientists, including researchers in Oxford, Sheffield and London, which showed that gene therapy can provide long-term protection for photoreceptor cells in an animal model of retinitis pigmentosa.

Mice lacking rhodopsin, the light sensitive pigment of rod photoreceptors, were used as an animal model of the condition. Four-week-old animals were given doses of a modified virus in one eye in order to make their retinas produce a human protein, called ciliary neurotrophic factor (CNTF).

CNTF acts in the nervous system and has been investigated as a treatment in conditions such as amyotrophic lateral sclerosis (known ALS or Lou Gehrig’s disease), but may be toxic at high doses.

Using a modified ophthalmoscope to monitor the retinas of mice, the researchers observed that CNTF preserved photoreceptors, but that the number of cone cells decreased rapidly between 8–24 weeks after treatment in animals who received a low dose of CNTF and control animals.

They were able to show that the photoreceptors preserved through the treatment retained their function and were able to signal correctly to the brain, as measured by the response of mice to visual stimuli.

“Our results in this mouse model of retinitis pigmentosa clearly show that CNTF treatment can both give life-long protection to cone photoreceptors and preserve useful vision... this is a very promising study,” said lead researcher Professor Robert MacLaren, professor of ophthalmology at the Nuffield Laboratory of Ophthalmology.

Gene activity 

More than six months later, genetic analysis showed that in mice which received high-dose CNTF a number of genes linked with retinal disease were almost 90-times more active than in the control mice.

Professor MacLaren added: “Our results suggest that directly increasing activity in the class of genes that were upregulated in our high-dose CNTF group has the potential to provide a novel, targeted treatment for retinitis pigmentosa and a range of neurodegenerative diseases.”

The research was funded by a number of organisations including the Wellcome Trust, the Medical Research Council and Fight for Sight.

Commenting on the findings, director of research for Fight for Sight, Dr Dolores M Conroy, said: “One of the most exciting prospects about these results is that the CNTF treatment was able to preserve vision even though rod degeneration had begun. This is a top priority for people with inherited and progressive eye conditions such as retinitis pigmentosa and AMD.”

Dr Conroy added: “As with any new line of research there is still a long way to go before any treatment could reach the clinic, but it is certainly possibly to look ahead and see that there will be a day when we can prevent sight loss with complex genetic involvement.”

The research is published in the journal Molecular Therapy.

Image: Rick Eh?/Flickr


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