Wednesday, 8 July 2015

Vitamin A key to preventing stargardt's

Stopping vitamin A from forming toxic clumps could slow down the progression of Stardgardt disease, according to new research from the University of Oxford.
Stargardt’s affects an estimated one in 10,000 people, affecting children as young as six. The condition causes degeneration of the macula, leading to a build up of lipofuscin in the retinal pigment epithelium (RPE) and gradual loss of central vision.
In people with Stargardt’s, toxic clumps can form from vitamin A through a process called dimerisation, which had been suggested as a cause of the disease.
Collaborating with researchers at Columbia University in New York, a team at Oxford hypothesised that these clumps cause chronic inflammation, and exacerbate the accumulation of lipofuscin and the premature ageing process in the retina.
To test their theory, the researchers tinkered with vitamin A by switching hydrogen for a heavier form of the atom, called deuterium, at a key point in the molecule. When the modified vitamin A was given to mice displaying Stargardt’s symptoms (lacking the ABCA4 gene), it did not form the clumps and subsequently reduced the amount of lipofuscin build up in the retina – reducing the inflammation and progression of the disease.
Dr Peter Charbel Issa, who led the team and is now at the University of Bonn in Germany, said: “An important discovery was that vitamin A dimerisation is responsible for around half of the lipofuscin found in the RPE. While others had suggested it might be a cause, we have confirmed that it is an important factor. If we can reduce the rate at which vitamin A dimerises, we could reduce the genetically-induced build-up of lipofuscin and slow down the progress of retinal degeneration.”
Dr Charbel Issa explained: “We also wanted to check if the altered vitamin A could cause any side-effects in humans that might affect sight in another way, for example by damaging peripheral or low-light vision. However, tests showed that this was not the case – there was no adverse outcome in both normal and mutant mice fed the deuterated vitamin A.”
Professor Robert MacLaren, an eye specialist who supervised the project at the Nuffield Laboratory of Ophthalmology, added: “Stargardt disease affects many children I see in my clinic and ABCA4-related retinal degenerations are also common in adults. The finding that a safe and simple dietary modification may help them is extremely promising. Dr Charbel Issa is to be congratulated for undertaking this incredibly detailed analysis that has provided further scientific validation of inhibiting vitamin A dimerisation in this disease. We look forward to the next step of clinical trials.”
Commenting on the findings, eye health campaigns officer at the RNIB, Dr Maria Lawson, said: “This is a promising piece of research as Stargardt's disease can cause severe problems with a person's central vision and there is currently no treatment for the condition.
“Finding an effective therapy that slows down this degenerative disease could make a huge difference to the lives of many people, especially the younger people affected by the condition.
“This research is still at an early stage but it will be exciting to watch how it progresses and to fully understand how this could help people with Stargardt's disease.”
The research is published in the journal PNAS