Phenotypic Rescue of Neuronal Structure and Function in a Rett Syndrome Mouse Model

Rett syndrome is a debilitating neurodevelopmental disorder that affects between one in 10,000 to one in 15,000 females. Symptoms that appear in early childhood include severe mental disabilities, impaired speech and movement, and seizures. Individuals with Rett syndrome show abnormalities in the size and structure of certain neurons in the brain. At present, there is very little treatment available for this disease. In most patients, Rett syndrome is caused by mutations in a single gene called MECP2. David Stuss’ research is part of a collaborative effort that is investigating methods for introducing a functional form of this gene into the brain at the appropriate developmental stage. This is expected to allow neurons to follow their normal course of growth and maturation. The methods being developed use engineered lentivirus vectors that are capable of delivering genetic material into differentiated, non-dividing cells like neurons. These viral vectors can also introduce genes for fluorescent proteins into targeted cells at the same time, allowing detailed microscopic visualization of the effects of treatment on neuronal structure. If the rescue of neuronal structure and brain development following therapeutic gene transfer can be demonstrated, this research will be an important first step in creating a therapeutic strategy for treating the devastating effects of Rett syndrome in children.