Featuring the work of CURE Grantee Jack Parent and Lori Isom
New stem cell research reveals dangerous cardiac effects of a gene mutation in patients with Dravet syndrome
Imagine putting your child to bed, only to have them pass away inexplicably in their sleep. This is the chilling reality for many victims of sudden unexpected death in epilepsy, or SUDEP — which claims the lives of 1 in every 1,000 people with epilepsy or other seizure disorders.
Patients with a rare disease called Dravet syndrome are at heightened risk for SUDEP. In the disease, seemingly healthy infants develop frequent and prolonged seizures, catastrophically affecting their development and quality of life.
Michigan Medicine scientists have been on a quest to better understand the connection and potential ways to prevent SUDEP in this population.
Eighty percent of patients with Dravet syndrome have variants in a gene, SCN1A, which codes for Nav1.1 sodium channels in the heart and the brain. Sodium channels are like a gate that allows sodium ions across a cell membrane, producing an electrical charge.
SCN1A mutations in people with Dravet syndrome result in electrical disturbances inside cells. Although seizures are the result of abnormal electrical signals in the brain, researchers suspected that problems may arise in the heart as well.
“We had a hypothesis that since these kids have the same mutation in their sodium channels in the heart and brain, they might have cardiac arrhythmias,” says Lori Isom, Ph.D., chair of the Department of Pharmacology at Michigan Medicine. “We were able to gather evidence that they do.”
The work is published in the journal Stem Cell Reports.
Isom and her clinical colleague, Jack M. Parent, M.D., professor of neurology and co-director of the Comprehensive Epilepsy Center at U-M, first looked to mouse models and then at cells collected from children with Dravet syndrome.
Their discovery: Mutations associated with Dravet syndrome in mice led to irregularities in the heart muscle’s sodium channels.