Base editing corrects genetic mutation responsible for severe form of inherited epilepsy

University of Virginia School of Medicine scientists have used a next-generation form of gene editing to fix the underlying cause of a severe form of epilepsy in lab mice. Their promising results suggest the approach could eventually be used to treat – or cure – severe genetic epilepsies in people as well.

Researchers led by UVA's Manoj Patel, PhD, used highly precise "base editing" to correct the gene mutation responsible for a severe form of inherited epilepsy known as SCN8A developmental and epileptic encephalopathy (DEE). The condition causes seizures, learning disabilities and movement problems, and it can also trigger sudden death.

"Historically, treatments addressed only the downstream effects of genetic mutations; today, we can correct the mutations themselves, targeting the root cause of disease," said Patel, part of UVA's Department of Anesthesiology and the UVA Brain Institute. "Base editing opens the door to the treatment of numerous genetic diseases, not only those associated with epilepsy, and has the potential to significantly improve patients' quality of life."

SCN8A-related epilepsy is estimated to affect 1 in 56,000 births – approximately 1% of all epilepsies – though many experts believe the condition is underdiagnosed. A mutation in the SCN8A gene allows too much sodium to flow into neurons in the brain, which causes the nerve cells to become hyperexcited. This leads to seizures which often resist treatment, as well as to physical and mental developmental problems.