ACTX-101 in Rett syndrome
ACTX-101 is an AAV9-delivered X-reactivation gene therapy for the treatment of the X-linked genetic disorder Rett syndrome.
Rett syndrome is a neurodevelopmental disorder affecting approximately 1 in 10,000 girls. Clinical manifestations typically appear between 6 to 18 months of age and consist of deficits of speech, purposeful hand movements, walking, eating, and breathing. Rett is often accompanied by repetitive hand movements such as hand wringing and clapping. There is currently no cure for Rett syndrome, and motor and cognitive function decline progressively after symptom onset. Breathing dysfunction is a leading cause of morbidity and mortality. Available therapeutics aim to manage symptoms.
Rett syndrome is caused by mutations in the MeCP2 gene. In females, ACTX-101 reactivates the silenced X chromosome in each cell, thereby restoring functional MeCP2 levels in cells with the active mutant X chromosome. At the same time, ACTX-101 does not cause MeCP2 overexpression in cells with active healthy X chromosome. Restoration of functional MeCP2 levels has been shown to slow or reverse progression of the phenotypic abnormalities, including breathing-related symptoms, in a mouse model of the disease.