Researchers successfully use an adeno-associated viral vector to restore brain function in a mouse model of SCN1B-linked DEE52, reducing seizures and extending lifespan, paving the way for future gene therapy in patients.
Study: Neonatal but not Juvenile Gene Therapy Reduces Seizures and Prolongs Lifespan in SCN1B-Dravet Syndrome Mice. Image Credit: Natali _ Mis/Shutterstock.com
Developmental and epileptic encephalopathies (DEE) are a group of severe disorders characterized by frequent seizures and resulting intellectual and developmental disabilities, often with a genetic basis.
One such condition is Dravet syndrome (DS), which typically emerges within the first year of life. A recent study published in the Journal of Clinical Immunology highlights the potential benefits of neonatal gene therapy in a DS mouse model.
Introduction
DS is primarily caused by mutations in the SCN1A gene, which encodes the α subunit (Nav1.1) of the voltage-gated sodium channel (VGSC) in neuronal cell membranes. However, mutations in SCN1B can also lead to DS or a more severe form of DEE, known as early infantile DEE52.
These seizures are resistant to conventional treatments and are associated with a high risk of mortality during episodes.
The missing protein in DEE52 is the β1 subunit of the VGSC, essential for neuronal excitation and modulation of sodium ion flow through both VGSCs and voltage-gated potassium channels. This subunit plays a critical role in brain and heart development by regulating excitable properties and gene transcription.
In mice lacking Scn1b, a condition resembling DEE52 develops, characterized by spontaneous whole-body seizures, failure to thrive, ataxia, and cardiac