A glimmer of hope for children facing blindness

The parents of eight-year-old Finley, who has lost most of her central vision, set up the RDH12 Fund for Sight.

Whenever she dropped her toy or dummy, shed lean down to pick it up, but then freeze for a moment, unable to find it. In the kitchen, if the fridge was open andshe was looking at me, shed walk into the door it wouldnt appear in her peripheral vision. Yiota Charalambous is describing how she first began to suspect that her daughter Anna, then aged two, had a problem with her sight.

Bumping into objects that leap out of the snowstorm of faulty peripheral vision is a hazard that is painfully familiar to me, and others like me, who have the degenerative eye disorder retinitis pigmentosa (RP). The condition is the most common cause of blindness among working-age people in the west, affecting one in 3,500. Unlike Anna, though, most of us are not diagnosed until we are adults. I was 26 a fairly typical age to receive the fateful news.

Anna is anything but typical, in that she has a rare form of RP known as Leber congenital amaurosis (LCA). Though everyone with RP shares a similar fate partial or total blindness for most of us the deterioration occurs gradually over many years. Children with LCA get no such reprieve; they lose their sight rapidly, and most are totally blind by the time they are 20.

Anna is now four, and the latest tests on her retinas indicate that neither rods nor cones the two types of photoreceptor cell responsible for turning light into image signals are functioning. This means she should be totally blind, says Yiota, but images are still getting to her brain. They cant explain it. Though Anna still has some useful sight, how much longer she can confound her doctors isuncertain.

RP is actually an umbrella term for dozens of different inherited retinal dystrophies. More than 50 associated genes have been identified so far, but multiple different mutations within these genes can cause the condition, and there is a long way to go before every mutation is isolated. A sample of my DNA is now somewhere in a long queue of test tubes at Moorfields eye hospital waiting to be screened; even when it is, the chance of pinpointing my particular genetic glitch is only 50/50. A wellspring of hope for Annas family is that the mutation causing her sight loss is known, understood, and already the subject of intensive study.

The gene in question is called RDH12, and it is responsible for encoding an enzyme that breaks down toxins in the retina. Without this enzyme, toxins accumulate, function is disrupted and cells begin to die. LCA affects one in 100,000 people, but worldwide there are only around 1,800 reported cases of this particular form of LCA, known as RDH12 LCA including the 21 children of the 15 families who constitute the US-based support group, the RDH12 Fund for Sight. Together, these families are striving to raise enough money to pay for the medical research on which all their hopes are pinned.

The group was set up by Mat and Jennifer Pletcher, from Boston, Massachusetts, in 2010, when their daughter Finley, then aged four, was diagnosed with the RDH12 LCA. Finley, now eight, has since lost most of her central vision, and Mat fears that as her sight has ebbed away so too has her confidence: Out on the playground, its a struggle for her to find the kids she knows because she just cant see well enough. Often shell opt to just play by herself because its easier.

The area of research where most headway has been made is in gene therapy. In 2007, a small group of patients affected by a mutation in the RPE65 gene became the first to have a corrective version of the gene inserted into their retina using a virus vector. None suffered adverse effects, and one experienced an improvement in night vision demonstrating proof of principle. Lead researcher Professor Robin Ali explains that the next trial will use a more potent vector and should move the research a vital step closer to the licensing of a drug capable of preserving daytime vision and slowing degeneration a goal that he believes is attainable within three or four years.

Where does this leave parents whose children are affected by the more aggressive RDH12 form of the disease? Do they have grounds for hope? Yes. We are committed to developing a trial [with RDH12], says Professor Ali. We have shown proof of concept in a mouse model, and we are moving to the next stage.

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A glimmer of hope for children facing blindness