University of Virginia School of Medicine researchers have used an advanced gene-editing technique to correct the underlying cause of a severe form of epilepsy in lab mice. This breakthrough could one day lead to new treatments or cures.
“Historically, treatments addressed only the downstream effects of genetic mutations; today, we can correct the mutations themselves, targeting the root cause of disease,” said Manoj Patel, part of 鶹ƽ 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 improve patients’ quality of life significantly.”
Manoj Patel, part of 鶹ƽ Department of Anesthesiology and the UVA Brain Institute, says advances in gene therapy show promise for treating inherited epilepsies, though more research is needed before use in people. (Contributed photo)
Patel led the research team that used gene editing to correct the DNA change behind SCN8A developmental and epileptic encephalopathy. This serious inherited disorder can cause seizures, learning and movement difficulties and sometimes sudden death. The work received support from the National Institutes of Health, the UVA Brain Institute and the Ivy Biomedical Innovation Fund.
The team’s findings suggest correcting disease-causing mutations directly could offer a new path forward for treating severe genetic epilepsies and other inherited conditions.
Targeting the disease at its source
SCN8A-related epilepsy is a rare condition that affects about 1 in 56,000 births – roughly 1% of all epilepsies. Experts believe many cases go undiagnosed. A change in a gene that lets too much sodium enter brain cells, making them overactive, is the cause of the condition. The condition can lead to seizures that are often hard to treat, along with physical and cognitive developmental challenges.
Symptoms typically appear in early infancy, but the severity can vary widely. In the most serious cases, the condition carries a significant risk of sudden, unexpected death.
Because of its severity and the fact that seizures often do not respond well to medication, Patel and his team targeted the underlying cause to find better treatment options. They turned to base editing, a technique that allows scientists to make precise changes to DNA by altering single building blocks of genes.
The high precision of base editing allows scientists to avoid unwanted side effects that can accompany gene editing. Patel and his team used the approach to correct the mutation in their lab mice, finding that it either eliminated or dramatically reduced seizures and increased overall survival. It also improved the mice’s ability to move and reduced anxiety-like behaviors, which are used as proxies for assessing cognitive benefits.
