Delivering healthy genes to people with Rett syndrome may lead to the reversal of this syndrome according to research published August 21. Using gene therapy, researchers were able to reverse the symptoms of Rett syndrome in mice, reports lead researcher Gail Mandel of Oregon Health and Science University. The research results, published in the Journal of Neuroscience, are particularly significant as the techniques used “have potential for clinical application.”
Rett syndrome is a rare neurodevelopmental disorder according to the National Institute of Neurological Disorders and Stroke. The disorder that is primarily caused by a genetic mutation, mainly affects girls. Some of the major symptoms of Rett syndrome are:
- Slowed growth
- Loss of motor functions
- Loss of communication and thinking abilities
- Breathing problems
- Intellectual disability
Prior to the publication of the latest version of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Rett syndrome was classified as an autism spectrum disorder. There is no cure for Rett syndrome. Treatment focuses on the "management of symptoms."
The current research builds on earlier work done by Adrian Bird of the University of Edinburgh. Bird, who is co-author of the current study, established the principle of reversing Rett syndrome in 2007. That research, “Reversal of Neurological Defects in a Mouse Model of Rett Syndrome,” was published in the journal Science.
Mandel and her colleagues targeted the MECP2 gene which, when mutated, causes Rett syndrome. They used a virus (AAV9) to introduce the “critical segments” of the MECP2 gene into mice with Rett syndrome. After receiving the virus intravenously, the Rett mice “showed profound improvements in motor function, tremors, seizures and hind limb clasping.”
“Gene therapy is well suited for this disorder,” Dr. Mandel explains.“Because MECP2 binds to DNA throughout the genome, there is no single gene currently that we can point to and target with a drug. Therefore the best chance of having a major impact on the disorder is to correct the underlying defect in as many cells throughout the body as possible. Gene therapy allows us to do that.”
Mandel cautioned that further research is needed. “Our study is an important first step in highlighting the potential for AAV9 to treating the neurological symptoms in Rett. We are now working on improving the packaging of MeCP2 in the virus to see if we can target a larger percentage of cells and therefore improve symptoms even further,” said Mandel.
The study is reported in the article “Systemic delivery of MeCP2 rescues behavioral and cellular deficits in female mouse models of Rett syndrome.”