What is SCN2A?
SCN2A is a gene that provides instructions for making a sodium channel protein called NaV1.2. These sodium channels are primarily found in neuronal cells throughout the brain. NaV1.2 controls the flow of sodium ions into cells, which makes it possible for neurons to communicate by generating and transmitting electrical signals, called action potentials. Action potentials enable everyday functions, such as the ability to move and think.
Mutations in SCN2A alter the sodium channel function, leading to a group of brain disorders. There have been significant advances in our understanding of how different mutations in SCN2A contribute to the different forms of brain disorders.
When the mutation alters the sodium channel in a way that it increases the flow of sodium ion into neurons, leading to abnormal increase of neuronal activity in the brain (or hyperexcitability), the mutation is classified as “gain-of-function.” Gain-of-function SCN2A mutations generally result in seizures that begin earlier in life, typically within the first 3 months, as well as significant delays in reaching developmental milestones. On the other hand, if the mutation leads to a decreased flow of sodium ions and reduced neuronal activity, the mutation is classified as “loss-of-function.” Loss-of-function SCN2A mutations generally result in autism, developmental delay, and sometimes seizures that begin later in life. Both groups of patients may also have sensory dysfunction, movement disorders, poor muscle tone (hypotonia), gastrointestinal issues, and other complications.
While there are treatments that help some patients with the symptoms of SCN2A disorders, such as seizures, none of them target the underlying cause of disease, the genetic mutation itself. However, advances in research, specifically in genetic research and precision medicines, are leading to important discoveries and innovations for people living with SCN2A disorders.
Praxis is currently developing 2 novel investigational medications, PRAX-222 and PRAX-562, both specifically designed for gain-of-function SCN2A epilepsies. Learn more about PRAX-222 and PRAX-562.
Precision medicine for SCN2A disorders
Precision medicine is a way to treat patients based on factors that are specific to them, such as the genetic causes of their disease. Different gene mutations underlie different human diseases. Precision medicines that target the SCN2A gene specifically may allow us to manage these disorders more effectively.