Scottish scientists have discovered a way to reverse the symptoms of Rett Syndrome (RS), the most disabling autism spectrum disorder by targetting a gene in mice.
The study was performed by researchers based at Edinburgh and Glasgow Universities and is published in the journal Science.
Dr Stuart Cobb, a Neuroscientist from the University of Glasgow’s Faculty of Biomedical and Life Sciences, and member of the research team, called the discovery a breakthrough that brings a “small piece of hope” for sufferers of RS and their families.
Rett Syndrome affects some 10,000 children in the UK (or 1 in every 10,000 to 15,000 children according to the US National Institutes of Health). It is an untreatable neurological disorder that leaves sufferers, who are mostly female, severely disabled.
Babies born with RS usually develop normally up to 18 months and then they regress, losing speech and the ability to move easily. They often go on to develop more severe debilitating symptoms such as repetitive movements, seizures and problems with breathing and controlling motor functions.
Scientists had already suspected that RS was caused by a mutant form of the gene Mecp2, which works by switching other genes on and off. In fact the same scientist that led this latest study, Professor Adrian Bird, was the one who discovered it in 1989.
In this latest study however, Professor Bird and his colleagues were able to show that by targetting Mecp2 in mice with RS, even adult mice, they could make the gene work normally and cause reversal in the RS symptoms.
Calling the results “astonishing and completely unexpected,” Dr Stuart Cobb said they were able to show how the underlying neurological malfunction in the brain was restored, “Analysing the communication between nerves in the brain, we discovered that abnormal signalling is also rectified when MECP2 gene is switched back on,” he said.
The symptoms began to reverse straight away. Motor control and breathing improved and within weeks it was difficult to tell which mice had once had RS and which had not.
By reversing the symptoms in adult mice the study showed that RS is not caused by abnormal development but by a malfunction that can be repaired. RS is not a degenerative disease since neurons are left intact. “Having demonstrated the concept of reversibility, it is hoped that the current breakthrough will encourage further research to discover a treatment,” said Dr Cobb.
Perhas gene therapies could be developed that suppress the mutated version of Mecp2 and activate a healthy version. Or they could take the form of drugs that suppress the action of proteins coded by a mutant Mecp2.
The breakthrough that has been achieved with this study is profound when one considers the possibility that other neurological disorders with similar causes might be reversible. This concerns the issue of what the researchers call “phenotypic reversibility”, where the effect of a faulty gene can be reversed. Their overriding conclusion is that this study firmly and robustly establishes that this is possible because the symptoms of RS were reversed not only in young but also adult animals.
Chris James, Director of the UK’s Rett Syndrome Association, which helped to fund the research, said the Association was delighted with the news. He acknowledged that it is early days, but said that it was a big step toward developing future therapies and that it should “give hope to those families affected by Rett syndrome.”
“Reversal of Neurological Defects in a Mouse Model of Rett Syndrome.”
Jacky Guy, Jian Gan, Jim Selfridge, Stuart Cobb, and Adrian Bird.
Published Online February 8, 2007
Science DOI: 10.1126/science.1138389
Click here for Rett Syndrome Association (UK).
Written by: Catharine Paddock
Writer: Medical News Today