How Toronto researchers are helping Rett syndrome patients


Could you imagine that overnight your young daughter lost her ability to speak or walk? Many parents of Rett syndrome children remember the exact day their daughter stopped developing normally. Rett syndrome is a genetic disorder that robs seemingly normal girls of their ability to speak, walk, or purposefully use their hands. One in about 20,000 girls are afflicted with this autism-spectrum disorder, making it the most common genetic cause of severe mental deficiency in girls worldwide. And like autism, it has no cure.

In a study entitled, “Targeted delivery of an Mecp2 transgene to forebrain neurons improves the behaviour of female Mecp2-deficient mice,” published online in Human Molecular Genetics, scientists at the Krembil Neuroscience Centre at Toronto Western Hospital have successfully corrected many of the behavioural deficits in a mouse model of Rett syndrome.

Using a laboratory process similar to gene therapy, Dr. James Eubanks, senior scientist, and his research team corrected the genetic abnormality by replacing the malfunctioning form of the gene responsible for Rett syndrome with a working copy of the gene in the brain.

“This is an important discovery because it is the first time scientists have shown in females that an x-linked neurological condition can be improved through gene transfer procedures,” says Dr. Eubanks. “We know which particular gene causes Rett syndrome, and now we know that restoring its function in the female brain can improve the condition. Until now we were not sure if Rett syndrome could be treated. Our work suggests that future treatment is tangible.”

Dr. Andreas Rett of Austria coined the genetic disorder in 1966, but it remained relatively unknown until 1983 when Dr. Bengt Hagberg published an article describing the syndrome in Annals of Neurology.

The first symptoms of Rett syndrome usually appear between six and18 months of age when children exhibit social withdrawal associated with autism, or they may be considered colic-babies. The gene responsible for Rett syndrome resides on the x-chromosome, explaining why females are primarily affected. The most recognizable signs of the disease are the loss of acquired language, disappearance of motor skills, compulsive hand wringing and the loss of functional hand use. Many children become wheelchair bound.

Although some individuals with Rett syndrome die at a young age, most live into adulthood and undergo changes in disease progression including increasing neurological deficits like apraxia (the inability to organize voluntary movement), Parkinson-like tremors, breathing problems and inability to chew or swallow. Patients with Rett syndrome often have seizures and have difficulty recovering from stress. For example, stress responses such as increased heart rate or sweating persist long after the stressor is gone.

Dr. Eubanks and his team hope this new research will not only increase awareness of Rett syndrome, but also lead to new treatment strategies. “The work in animal models shows that improving Rett syndrome is feasible,” says Dr. Eubanks. “The next step is to develop strategies that will enable our research to be translated into clinical practice.”