Published online 28 April 2008 | Nature | doi:10.1038/news.2008.786

News: Briefing

Gene therapy treats blindness

This weekend two teams reported success in helping people to see again. Nature News catches up on the state of gene therapy trials against blindness.

Seeing the light: gene therapy helped this 18-year-old to see better in dim light.AP Photo/BBC

What sort of blindness do the new reports address?

Two separate teams have published reports of successful gene therapy trials for a type of Leber’s congenital amaurosis (LCA), a rare inherited form of blindness. Patients with LCA have a genetic defect that affects the development of the light receptors in their eyes; typically they have poor vision at birth and are blind within three decades. Some 3,000 people are thought to be affected in the United States.

Were the patients 'cured'?

In one study, led by husband and wife team Jean Bennett and Albert Maguire at the University of Pennsylvania in Philadelphia, three patients received the treatment and all three showed some improvements in vision1: they went from being able to detect hand movements to being able to read lines on an eye chart, the team reports.

In the other study, a team based at London’s Moorfields Eye Hospital and University College London also treated three patients, and were able to help an 18-year-old man who had extremely limited vision in poor light conditions; trials in a dimly-lit maze showed his vision had markedly improved. This despite the fact that the trial's primary aim was to assess the safety of the therapy, and not its clinical effects2. “What we were really surprised by was that we saw a clinically significant effect,” says Robin Ali, who led the study. Both reports appear in the New England Journal of Medicine1,2.

How does it work?

The idea of this type of gene therapy is to insert a normal copy of a gene into cells that have a faulty or missing version, restoring the cells’ normal function. In the type of LCA the two groups studied, a gene called RPE65 is mutated, making light-sensitive cells in the eye unable to capture light and transmit information about it to the brain. In early stages it mainly affects the group of photoreceptors referred to as rods, which are more numerous and more sensitive to light than those sensitive to colour. In the new studies, both groups got the RPE65 gene into the retina by packaging it inside a harmless virus and then injecting this virus into the eye. When the virus 'infects' retinal cells, the gene is transferred and can theoretically start functioning normally. This should allow the right proteins to be made for functioning photoreceptors, providing that the retinal cells are still alive for the gene to be active within.

Has gene therapy been trialled for blindness before?

Yes, but for a different type of blindness, and using a different mode of action. Another eye disease called age-related macular degeneration, in which blood vessels grow across the eye and obscure vision, has been targeted with a technique that silences a particular gene (as opposed to inserting one). In 2006, a clinical trial of a drug called Bevasiranib demonstrated that interfering with a gene called VEGF reduced blood vessel growth and could improve vision slightly in such cases. Gene therapy has also been tried for a type of eye cancer called retinoblastoma.

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What other treatments are being investigated for severe blindness?

Blindness has many different causes, so there are several molecular treatments being pursued. In a paper published in Nature Neuroscience this week, for example, Botond Roska at the Friedrich Miescher Institute for Biomedical Research in Basel, Switzerland, and his team improved vision in blind mice that had lost all their photoreceptors by inserting a light-sensitive protein derived from a green alga into their eyes3.

Ali is confident that we’ll see more of his technique as it progresses through clinical trials. “This study paves the way for the use of the same technology for other inherited forms of retinal degeneration,” he says. They are currently trialling it in another 9 patients and hope to be close to licensing the method in about 2 years. 

  • References

    1. Maguire, A. M. et al. N. Engl. J. Med. doi:10.1056/NEJMoa0802315 (2008).
    2. Bainbridge, J. W. B. et al. N. Engl. J. Med. doi:10.1056/NEJMoa0802268 (2008).
    3. Lagali, P. et al. Nature Neurosci. doi:10.1038/nn.2117 (2008).
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