Rett syndrome: hopes of gene therapy | Children's Charity

Rett syndrome: hopes of gene therapy

First published on 23 October 2009

Updated on 26 June 2013

What did the project achieve?

“We have demonstrated that it may one day be possible to use an exciting approach known as gene therapy to treat children with a devastating disorder called Rett syndrome,” says Professor Adrian Bird.

“Rett syndrome typically begins unexpectedly in baby girls who are around six to 18 months old,” explains Professor Bird. “It causes profound physical and learning disabilities, depriving children of their speech and coordinated movement for the rest of their lives.”

Children with Rett syndrome can experience many other distressing problems too, such as seizures, breathing difficulties, anxiety and disturbed sleep. There is no cure and children need 24-hour care for life.

“Rett syndrome almost always results from changes – or mutations – in a single gene,” explains Professor Bird. “Gene therapy involves delivering healthy copies of a particular gene to the body. Along with collaborators in the United States, we have shown that gene therapy can correct the symptoms of Rett syndrome in a laboratory model of the disorder. Many technical hurdles remain, and more laboratory work is needed, but our work is a step towards developing a badly needed new treatment for this devastating disorder.”

This research was completed on 30 September 2012

Rett syndrome is a devastating, developmental disorder that causes profound physical and learning disabilities, typically striking unexpectedly in girls of less than 18 months old. Sadly, there is no cure, and most sufferers need total, 24-hour care for life. In 2007, researchers made the breakthrough discovery that a form of genetic manipulation can reverse symptoms in a laboratory model of Rett syndrome. Now, they hope to provide proof of principle that gene therapy may one day benefit children with Rett syndrome.

What's the problem and who does it affect?

Devastating regression

Rett syndrome is a very serious developmental disorder, which mostly affects little girls. Affected babies typically seem healthy at birth and begin to develop normally, often learning how to walk, play happily and say their first words.

But then, at around six to 18 months of age, a devastating regression begins. Babies lose their ability to speak, they begin to lose control of their movement, particularly their hands, and there is a marked deceleration of head growth. Babies start making stereotyped hand movements, often wringing their hands compulsively, and their posture becomes awkward.

Sadly, little girls with Rett syndrome can go on to suffer a shocking range of problems, including seizures, Parkinsonian tremors, disturbed breathing, heart and digestive problems, curvature of the spine and fragile bones. Many girls suffer bouts of extreme anxiety, mood swings and disturbed sleep, and they often go through a period of withdrawal, when they cry inconsolably.

Most affected children become totally dependent on others for round-the-clock care. Treatments, which focus on tackling individual symptoms, include medication for seizures and anxiety, feeding tubes, extensive occupational therapy, physiotherapy and surgery. There is no cure.

What is the project trying to achieve?

Building on a groundbreaking discovery

For many years, Rett syndrome was widely regarded as an incurable disorder, as it was generally thought to cause irreversible changes in the brain. Then, in 2007, came the astonishing discovery that it was possible to reverse the symptoms of Rett syndrome in a laboratory model of the disorder, using a form of genetic manipulation.

Rett syndrome is caused almost exclusively by mutations – or faults – in a gene called MeCP2 (pronounced mec pea two). Researchers envisage a future therapy for Rett syndrome could work by repairing or replacing this faulty gene.

In this project, researchers are investigating the potential of such genetic manipulation in a laboratory model. They are correcting faults in the MeCP2 gene in particular areas of the brain and monitoring how such targeted intervention affects individual symptoms. They hope to find out, for example, whether targeting the brainstem cures breathing disturbances, and whether targeting the cerebellum corrects abnormal movements.

The researchers are also hoping to map out which parts of the brain are linked to each individual symptom of Rett syndrome.

What are the researchers' credentials?

Project LeaderProfessor A Bird CBE FRS FRSE
Project team
  • Dr Jim Selfridge PhD
LocationWellcome Trust Centre for Cell Biology, School of Biological Sciences, University of Edinburgh
Duration3 years
Grant awarded23 July 2009
Start date1 October 2009
End date30 September 2012
Grant amount£186,972.00
Grant codeSP4443, GN1755

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The project leader, Professor Adrian Bird, directed the groundbreaking research that showed, in 2007, that a form of genetic manipulation could reverse the symptoms of Rett syndrome in a laboratory model. His group also discovered the MeCP2 gene, back in 1990, which was later shown to have links with Rett syndrome.

Professor Bird is an outstanding scientist with an excellent track record. He is recognised worldwide as a leader in his field of research, and his successes have been recognised by the award of many prestigious honours, including the Louis-Jeantet Prize for Medicine and most recently the Charles Leopold Mayer Prize from the French Academy of Sciences.

Professor Bird’s research group consists of several talented and committed scientists from all over the globe, brought together for their expertise spanning molecular biology, biochemistry and transgenic technology. They are committed to unravelling how the MeCP2 gene works, and why problems with it cause Rett syndrome.

Who stands to benefit from this research and how?

New-found hope

The groundbreaking discovery that a form of genetic manipulation could reverse the symptoms of Rett syndrome in a laboratory model revolutionised thinking, giving all concerned new-found confidence to hope that, one day, there may be a cure for girls with Rett syndrome.

In this project, the researchers are helping to bridge the gap between the laboratory model and the patient. They are hoping to provide additional proof of principle that gene therapy has the potential to improve the lives of girls with Rett syndrome.

Around one in every 10,000 to 15,000 baby girls develops this debilitating illness, which devastates not only the child’s life, but those of family and carers too.1 A new therapy that reverses the symptoms of Rett syndrome, effectively curing the illness, would be truly life-changing. Currently, sufferers are totally reliant on intensive, lifelong support. Even a treatment that alleviates just one of the many disabling symptoms, such as the abnormal breathing or difficulties controlling hand movements, could bring significant improvements in a child’s quality of life.

References

  1. National Institute of Neurological Disorders and Stroke (NINDS), Rett Syndrome Fact Sheet, National Institutes of Health (NIH) Publication No 04-4863, June 6, 2008.
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